Drug linkers and drug conjugates

Abstract

Conjugates and uses thereof. Provided herein are drug-linkers of Formula (X) or a pharmaceutically acceptable salt thereof, wherein the variables of Formula (X) are as defined herein. Conjugates of such compounds can be used as anticancer agents. Formula (X)

Description

Cross-references

[0001] This application claims the following rights: U.S. Provisional Patent Application No. 63 / 503,387, filed on May 19, 2023; U.S. Provisional Patent Application No. 63 / 535,991, filed on August 31, 2023; U.S. Provisional Patent Application No. 63 / 606,521, filed December 5, 2023; and U.S. Provisional Patent Application No. 63 / 558,052, filed on February 26, 2024; The full contents of each of these provisional applications are incorporated herein by reference. Background Technology

[0002] Currently, small cytotoxic molecules used in antibody-drug conjugates can include camptothecin derivatives, which have antitumor effects by inhibiting topoisomerase I. Camptothecin derivatives can be used in antibody-drug conjugates (ADCs). However, further development of camptothecin derivatives and ADC drugs with better efficacy and / or improved safety is still needed. Summary of the Invention

[0003] In one aspect, this disclosure provides a drug-connector of formula (X): Formula (X) Or its pharmaceutically acceptable salt, wherein; R 40 Independently selected from hydrogen, Y and ; D is selected from the drug unit; n is selected from 0 and 1; m is selected from 0 and 1; Where at least n or m is 1; p is selected from 0 and 1; z is selected from 0 and 1; X is selected from CH and N; Y is -OT 1 and -NH-T 2 ; T 1 For sugar-cuttable units; T 2 It is a peptide cleavable unit; S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20)C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 3 Selected from the spacer region, wherein the spacer region is preferably phenylene, wherein S 3 To indicate whether something exists or does not exist; S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement; Where M 1 K 1 K 2 S 1 S 2 S 3 and S 4 The optional substituents on the surface are selected independently each time they appear: (i) Halogen, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30)2、-NO2、=O、=S、=N(R 30 ) and -CN; (ii) C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles; and (iii) C 3-10 A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group; M 1 These are groups that can react with ligands to form linker units; K 1 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; wherein when X is CH, D is exatecan or MMAE, m is 1, n is 0, and K 1 It is polysarcosine, which contains 2-9 sarcosine or 13-30 sarcosine. K 2 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and Each R 30 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles.

[0004] In one respect, this disclosure provides a drug-connector of formula (I): Formula (I) Or its pharmaceutically acceptable salt, wherein; D is selected from the drug unit; n is selected from 0 and 1; m is selected from 0 and 1; Where at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is -OT 1 and -NH-T 2 ; T 1 For sugar-cuttable units; T 2 It is a peptide cleavable unit; S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 3Selected from the spacer region, wherein the spacer region is preferably phenylene, wherein S 3 To indicate whether something exists or does not exist; S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement; Where M 1 K 1 K 2 S 1 S 2 S 3 and S 4 The optional substituents on the surface are selected independently each time they appear: (i) Halogen, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 ) and -CN; (ii) C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles; and (iii) C 3-10 A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group; M 1 These are groups that can react with ligands to form linker units; K 1 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R)20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; wherein when X is CH, D is eczema or MMAE, m is 1, n is 0, and K 1 It is polysarcosine, which contains 2-9 sarcosine or 13-30 sarcosine. K 2 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and Each R 30 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles.

[0005] In one aspect, this disclosure provides a drug-connector of formula (Ia) or formula (Ib): Formula (Ia) Formula (Ib) Or a pharmaceutically acceptable salt thereof, wherein; D is selected from the drug unit; n is selected from 0 and 1; m is selected from 0 and 1; Where at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is -OT 1 and -NH-T 2 ; T 1 For sugar-cuttable units; T 2 It is a peptide cleavable unit; S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20)-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 3 Selected from the spacer region, wherein the spacer region is preferably phenylene, wherein S 3 To indicate whether something exists or does not exist; S 4 Selected from: (i) optional substitutions of C1-C 30Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement; Where M 1 K 1 K 2 S 1 S 2 S 3 and S 4 The optional substituents on the surface are selected independently each time they appear: (i) Halogen, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 ) and -CN; (ii) C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30-OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles; and (iii) C 3-10 A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group; M 1 These are groups that can react with ligands to form linker units; K 1 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; wherein when X is CH, D is eczema or MMAE, m is 1, n is 0, and K 1 It is polysarcosine, which contains 2-9 sarcosine or 13-30 sarcosine. K 2 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and Each R 30 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C3-12 Carbon rings and 3 to 12-membered heterocycles.

[0006] In one aspect, this disclosure provides conjugates of formula (XX): Formula (XX) Or its pharmaceutically acceptable salt, wherein; R 40 Independently selected from hydrogen, Y and ; D is selected from the drug unit; n is selected from 0 and 1; m is selected from 0 and 1; Where at least n or m is 1; p is selected from 0 and 1; z is selected from 0 and 1; X is selected from CH and N; Y is -OT 1 and -NH-T 2 ; T 1 For sugar-cuttable units; T 2 It is a peptide cleavable unit; S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20(iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 3 Selected from the spacer region, wherein the spacer region is preferably phenylene, wherein S 3 To indicate whether something exists or does not exist; S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement; Where M 2 K 1 K 2 S 1 S 2 S 3 and S 4 The optional substituents on the surface are selected independently each time they appear: (i) Halogen, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 ) and -CN; (ii) C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30)2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles; and (iii) C 3-10 A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group; L represents the target unit; M 2 For connection units; K 1 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; wherein when X is CH, D is eczema or MMAE, m is 1, n is 0, and K 1 It is polysarcosine, which contains 2-9 sarcosine or 13-30 sarcosine. K2 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and Each R 30 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles.

[0007] In one respect, this disclosure provides a conjugate of formula (A): Formula (A) Or its pharmaceutically acceptable salt, wherein; D is selected from the drug unit; n is selected from 0 and 1; m is selected from 0 and 1; Where at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is -OT 1 and -NH-T 2 ; T 1 For sugar-cuttable units; T 2 It is a peptide cleavable unit; S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20)-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 3 Selected from the spacer region, wherein the spacer region is preferably phenylene, wherein S 3 To indicate whether something exists or does not exist; S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement; Where M 2 K 1 K 2 S 1 S 2 S3 and S 4 The optional substituents on the surface are selected independently each time they appear: (i) Halogen, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 ) and -CN; (ii) C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles; and (iii) C 3-10 A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group; L represents the target unit; M 2 For connection units; K 1 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; wherein when X is CH, D is eczema or MMAE, m is 1, n is 0, and K 1 It is polysarcosine, which contains 2-9 sarcosine or 13-30 sarcosine. K 2 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and Each R 30 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles.

[0008] In one aspect, this disclosure provides conjugates of formula (Aa) or formula (Ab): Formula (Aa), Formula (Ab) or Or its pharmaceutically acceptable salt, wherein; D is selected from the drug unit; n is selected from 0 and 1; m is selected from 0 and 1; Where at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is -OT 1 and -NH-T2 ; T 1 For sugar-cuttable units; T 2 It is a peptide cleavable unit; S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 3 Selected from the spacer region, wherein the spacer region is preferably phenylene, wherein S 3 To indicate whether something exists or does not exist; S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement; Where M 2 K 1 K 2 S 1 S 2 S 3 and S 4 The optional substituents on the surface are selected independently each time they appear: (i) Halogen, -OR 30 -N(R) 30 )2、-SR30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 ) and -CN; (ii) C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles; and (iii) C 3-10 A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30-S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group; L represents the target unit; M 2 For connection units; K 1 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; wherein when X is CH, D is eczema or MMAE, m is 1, n is 0, and K 1 It is polysarcosine, which contains 2-9 sarcosine or 13-30 sarcosine. K 2 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and Each R 30 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles.

[0009] In one aspect, this disclosure provides a method of treating a subject suffering from a disease or condition, comprising administering to a subject in need a drug-connector or salt of formula (I), formula (IA), formula (IB), formula (Ia), formula (I-AAa), formula (Ib), formula (I-AAb), formula (II-A), or formula (II-B) (each of which further comprises a targeting unit), or a conjugate or salt of formula (A), formula (Aa), formula (Ab), formula (A-1), formula (A-2), formula (A-3), or formula (A-4), or a pharmaceutical composition thereof. Incorporation

[0010] All publications, patents, and patent applications mentioned in this specification are incorporated herein by reference to the extent that each individual publication, patent, or patent application is expressly and individually indicated to be incorporated by reference. To the extent that any publication, patent, or patent application incorporated by reference conflicts with the disclosure contained in this specification, this specification is intended to supersede and / or give precedence to any such conflicting material. Attached Figure Description

[0011] The novel features of the invention are set forth in the appended claims. A better understanding of the features and advantages of the invention will be obtained by referring to the following detailed description of exemplary embodiments utilizing the principles of the invention, along with the accompanying drawings (also referred to herein as “Figures” and “Drawings”). In the Drawings: Figure 1 The figure illustrates the stability of different ADCs in mouse plasma; Figure 2 The figure illustrates the stability of different ADCs in human plasma; Figure 3 The figure shows the percentage of cell binding for different ADCs; Figure 4 The figure illustrates the median fluorescence intensity (MFI) of different ADCs bound to JeKo cells. Figure 5 The figure illustrates the percentage of inhibition of Jeko-1 cell growth by different ADCs; Figure 6 The diagram illustrates the internalization of different ADCs; Figure 7 The illustration shows the release of eczema from the ADC; Figure 8 The figure illustrates the in vivo antitumor activity of the ADC in the Jeko-1 xenograft model; Figure 9 The figure illustrates the in vivo antitumor activity of ADC in the H1975 xenograft model; Figure 10 The pharmacokinetic parameters of various ADCs are illustrated. Figure 11 The figure illustrates the stability of different ADCs in mouse plasma; Figure 12 The figure illustrates the stability of different ADCs in human plasma; Figure 13 The figure shows the percentage of cell binding for different ADCs; Figure 14 The figure shows the median fluorescence intensity (MFI) for different ADCs. Figure 15 The figure illustrates the percentage of inhibition of Jeko-1 cell growth by different ADCs; Figure 16 The diagram illustrates the internalization of different ADCs; Figure 17 The illustration shows the release of eczema from the ADC; Figure 18 The pharmacokinetic parameters of various ADCs are illustrated. Figure 19 Chiral HPLC chromatograms of compounds 37, 107-S, and 118-R; Figure 20 The figure illustrates the percentage of cell binding for different ADCs that bind to LCLC-103H cells; Figure 21 The figure illustrates the median fluorescence intensity of different ADCs bound to LCLC-103H cells; Figure 22 The diagram illustrates the quenching internalization of different ADCs; Figure 23 The figure illustrates the percentage of inhibition of Jeko-1 cell growth by different ADCs; Figure 24 The figure illustrates the percentage of growth inhibition of LCLC-103H cells by different ADC isoforms; and Figure 25 In vivo antitumor activity of ADC in the LCLC-103H xenograft model.

[0012] Figure 26 In vivo antitumor activity of ADC in the CTG-2215 xenograft model.

[0013] Figure 27 In vivo antitumor activity of ADC in the NCI-H526 xenograft model.

[0014] Figure 28 In vivo antitumor activity and dose titration of ADC in the LCLC-103H xenograft model. Detailed Implementation

[0015] The following description illustrates numerous exemplary configurations, methods, parameters, etc. However, it should be understood that such description is not intended to limit the scope of this disclosure, but is provided merely as a description of exemplary embodiments.

[0016] In the following description, certain specific details are set forth in order to provide a full understanding of the various embodiments of this disclosure. However, those skilled in the art will understand that this disclosure may be practiced without these details.

[0017] definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. All patents and publications cited herein are incorporated herein by reference.

[0018] "Alkyl" refers to a straight-chain or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, without any degree of unsaturation, and preferably having one to fifteen carbon atoms (i.e., C1-C1). 15 Alkyl group). In some embodiments, the alkyl group comprises one to thirteen carbon atoms (i.e., C1-C1). 13Alkyl group. In some embodiments, the alkyl group comprises one to eight carbon atoms (i.e., C1-C8 alkyl). In other embodiments, the alkyl group comprises one to five carbon atoms (i.e., C1-C5 alkyl). In other embodiments, the alkyl group comprises one to four carbon atoms (i.e., C1-C4 alkyl). In other embodiments, the alkyl group comprises one to three carbon atoms (i.e., C1-C3 alkyl). In other embodiments, the alkyl group comprises one to two carbon atoms (i.e., C1-C2 alkyl). In other embodiments, the alkyl group comprises one carbon atom (i.e., C1 alkyl). In other embodiments, the alkyl group comprises five to fifteen carbon atoms (i.e., C5-C6 alkyl). 15 Alkyl group. In other embodiments, the alkyl group comprises five to eight carbon atoms (i.e., C5-C8 alkyl). In other embodiments, the alkyl group comprises two to five carbon atoms (i.e., C2-C5 alkyl). In other embodiments, the alkyl group comprises three to five carbon atoms (i.e., C3-C5 alkyl). In some embodiments, the alkyl group is selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (isopropyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl), 1,1-dimethylethyl (tert-butyl), and 1-pentyl (n-pentyl). The alkyl group is attached to the rest of the molecule by a single bond.

[0019] Term "C" x-y "and "C x -C y When used in conjunction with a chemical part (such as alkyl, alkenyl, or ynyl), it means to include groups containing x to y carbons in the chain. For example, the term "C 1-6 "Alkyl" or "C1-C6 alkyl" refers to a substituted or unsubstituted saturated hydrocarbon group, including straight-chain alkyl and branched alkyl groups containing 1 to 6 carbons. The term -C x-y alkylene- or -C x -C y Alkylene refers to a substituted or unsubstituted alkylene chain containing x to y carbon atoms. For example, -C 1-6 The alkylene- or -C1-C6 alkylene- can be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, any one of which may be optionally substituted.

[0020] "Alkoxy" refers to a group of the formula -O-alkyl that is bonded by an oxygen atom, wherein the alkyl group is an alkyl chain as defined above.

[0021] "Alkenyl" refers to a straight-chain or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and preferably having two to twelve carbon atoms (i.e., C2-C2). 12Alkenyl group. In some embodiments, the alkenyl group comprises two to eight carbon atoms (i.e., C2-C8 alkenyl). In some embodiments, the alkenyl group comprises two to six carbon atoms (i.e., C2-C6 alkenyl). In other embodiments, the alkenyl group comprises two to four carbon atoms (i.e., C2-C4 alkenyl). The alkenyl group is attached to the rest of the molecule by a single bond, such as ethenyl (i.e., vinyl), propenyl (i.e., allyl), butenyl, pentenyl, pent-1,4-dienyl, etc.

[0022] "Alkyne group" refers to a straight-chain or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, and preferably having two to twelve carbon atoms (i.e., C2-C2). 12 The alkynyl group (C2-C8 alkynyl) is present in some embodiments. In other embodiments, the alkynyl group comprises two to six carbon atoms (C2-C6 alkynyl). In still other embodiments, the alkynyl group comprises two to four carbon atoms (C2-C4 alkynyl). The alkynyl group is attached to the rest of the molecule by a single bond, such as ethynyl, propynyl, butynyl, pentylyl, hexynyl, etc.

[0023] Term "C" x-y "Alkenyl" and "C" x-y "Alkyne" refers to a substituted or unsubstituted unsaturated aliphatic group whose length and possible substitutions are similar to those of the alkyl groups described above, but which contain at least one double or triple bond. Term -C x-y An alkenyl group refers to a substituted or unsubstituted alkenyl chain, wherein the alkenyl chain has x to y carbons. For example, a -C2-6 alkenyl group can be selected from vinylene, propenylene, butenylene, pentenylene, and hexenylene, any one of which may be optionally substituted. The alkenyl chain may have one or more double bonds. The term -C x-y An alkynyl group refers to an alkynyl chain with x to y carbons, whether substituted or unsubstituted. For example, -C2-6 alkynyl can be selected from ethynylene, propynylene, butynylene, pentyynylene, and hexynylene, any one of which may be optionally substituted. The alkynyl chain may have one or more triple bonds.

[0024] "alkylene" or "alkylene chain" refers to a straight-chain or branched divalent hydrocarbon chain in which the remainder of a molecule is attached to a free radical group consisting only of carbon and hydrogen, is unsaturated, and preferably has one to twelve carbon atoms, such as methylene, ethylene, propylene, n-butylene, etc. The alkylene chain is attached to the remainder of the molecule by single bonds and to the free radical group by single bonds. The attachment points of the alkylene chain to the remainder of the molecule and to the free radical group can be any two carbons in the chain. In some embodiments, the alkylene comprises one to ten carbon atoms (i.e., C1-C8 alkylene). In some embodiments, the alkylene comprises one to eight carbon atoms (i.e., C1-C8 alkylene). In other embodiments, the alkylene comprises one to five carbon atoms (i.e., C1-C8 alkylene). 1- In other embodiments, the alkylene oxide comprises one to four carbon atoms (i.e., C1-C4 alkylene oxide). In other embodiments, the alkylene oxide comprises one to three carbon atoms (i.e., C1-C3 alkylene oxide). In other embodiments, the alkylene oxide comprises one to two carbon atoms (i.e., C1-C2 alkylene oxide). In other embodiments, the alkylene oxide comprises one carbon atom (i.e., C1 alkylene oxide). In other embodiments, the alkylene oxide comprises five to eight carbon atoms (i.e., C5-C8 alkylene oxide). In other embodiments, the alkylene oxide comprises two to five carbon atoms (i.e., C2-C5 alkylene oxide). In other embodiments, the alkylene oxide comprises three to five carbon atoms (i.e., C3-C5 alkylene oxide).

[0025] "Alkenyl" or "alkenyl chain" refers to a straight-chain or branched divalent hydrocarbon chain in which the remainder of a molecule is attached to a free radical group consisting only of carbon and hydrogen, containing at least one carbon-carbon double bond, and preferably having two to twelve carbon atoms. The alkenyl chain is attached to the remainder of the molecule and to the free radical group via single bonds. The attachment points of the alkenyl chain to the remainder of the molecule and to the free radical group can be any two carbon atoms in the chain. In some embodiments, the alkenyl group contains two to ten carbon atoms (i.e., C2-C2). 10 (Alkenyl group). In some embodiments, the alkenyl group comprises two to eight carbon atoms (i.e., C2-C8 alkenyl). In other embodiments, the alkenyl group comprises two to five carbon atoms (i.e., C2-C5 alkenyl). In other embodiments, the alkenyl group comprises two to four carbon atoms (i.e., C2-C4 alkenyl). In other embodiments, the alkenyl group comprises two to three carbon atoms (i.e., C2-C3 alkenyl). In other embodiments, the alkenyl group comprises two carbon atoms (i.e., C2 alkenyl). In other embodiments, the alkenyl group comprises five to eight carbon atoms (i.e., C5-C8 alkenyl). In other embodiments, the alkenyl group comprises three to five carbon atoms (i.e., C3-C5 alkenyl).

[0026] "Imyynyl" or "Imyynyl chain" refers to a straight-chain or branched divalent hydrocarbon chain in which the remainder of a molecule is attached to a free radical group consisting only of carbon and hydrogen, containing at least one carbon-carbon triple bond, and preferably having two to twelve carbon atoms. The ynylyl chain is attached to the remainder of the molecule and to the free radical group via single bonds. The attachment points of the ynylyl chain to the remainder of the molecule and to the free radical group can be any two carbon atoms in the chain. In some embodiments, the ynylyl group contains two to ten carbon atoms (i.e., C2-C2). 10 The ynyl group (C2-C8 ynyl group) comprises two to eight carbon atoms in some embodiments. In other embodiments, the ynyl group comprises two to five carbon atoms (C2-C5 ynyl group). In other embodiments, the ynyl group comprises two to four carbon atoms (C2-C4 ynyl group). In other embodiments, the ynyl group comprises two to three carbon atoms (C2-C3 ynyl group). In other embodiments, the ynyl group comprises two carbon atoms (C2 ynyl group). In other embodiments, the ynyl group comprises five to eight carbon atoms (C5-C8 ynyl group). In other embodiments, the ynyl group comprises three to five carbon atoms (C3-C5 ynyl group).

[0027] "Aryl" refers to a free radical obtained from an aromatic monocyclic or polycyclic hydrocarbon ring system by removing a hydrogen atom from a carbon atom of the ring. An aromatic monocyclic or polycyclic hydrocarbon ring system contains only hydrogen and carbon, with 5 to 18 carbon atoms, and at least one ring in the system is aromatic; that is, according to Hückel's theory, it contains cyclic, delocalized (4n+2) rings. - Electronic system. The ring system of derived aryl groups includes, but is not limited to, groups such as benzene, fluorene, indene, indene, tetrahydronaphthalene, and naphthalene.

[0028] "Aryl group" refers to the formula -R c -aryl radicals, where R c It is an alkylene chain as defined above, such as methylene, ethylene, etc.

[0029] "Aryl" refers to the formula -R d -aryl radicals, where R d It is an alkenyl chain as defined above. "Arynyl group" refers to the formula -R e -aryl radicals, where R e It is an alkyne chain as defined above.

[0030] "Activated" "Group" refers to a cyclic alkyne that is highly reactive to azide groups due to ring strain in order to form a triazole.

[0031] "Activated disulfide" refers to a disulfide that can react with a mercapto group to form a new disulfide bond.

[0032] A "carbocyclic ring" refers to a saturated, unsaturated, or aromatic ring in which every atom is carbon. Carbocyclic rings can include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. Each ring in a bicyclic carbocyclic ring can be selected from saturated, unsaturated, and aromatic rings. Aromatic rings (e.g., phenyl) can be fused with saturated or unsaturated rings, such as cyclohexane, cyclopentane, or cyclohexene. The definition of a carbocyclic ring includes any combination of saturated, unsaturated, and aromatic bicyclic rings (provided the valence state allows). Exemplary carbocyclic rings include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. Bicyclic carbocyclic rings can be fused, bridged, or spirocyclic systems. In some cases, spirocyclic carbocyclic rings have at least two molecular rings with only one common atom.

[0033] "Carbocyclic alkene" refers to a divalent carbon ring in which the rest of the molecule is attached to a free radical group.

[0034] The term "unsaturated carbide ring" refers to a carbide ring having at least one degree of unsaturation and not containing aromatic carbocyclic rings. Examples of unsaturated carbocyclic rings include cyclohexadiene, cyclohexene, and cyclopentene.

[0035] “Cycloalkyl” refers to a fully saturated monocyclic or polycyclic hydrocarbon group consisting only of carbon and hydrogen atoms, including fused ring or bridged ring systems, and preferably having three to twelve carbon atoms. In some embodiments, the cycloalkyl group contains three to ten carbon atoms. In other embodiments, the cycloalkyl group contains five to seven carbon atoms. The cycloalkyl group can be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkyl groups include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of polycyclic cycloalkyl groups include, for example, adamantyl, norbornyl (i.e., bicyclo[2.2.1]heptyl), norbornenyl, decahydronaphthyl, 7,7-dimethylbicyclo[2.2.1]heptyl, etc.

[0036] "Cycloalkenyl" refers to an unsaturated, non-aromatic monocyclic or polycyclic hydrocarbon group consisting only of carbon and hydrogen atoms, including fused ring or bridged ring systems, preferably having three to twelve carbon atoms, and containing at least one double bond. In some embodiments, the cycloalkenyl group contains three to ten carbon atoms. In other embodiments, the cycloalkenyl group contains five to seven carbon atoms. The cycloalkenyl group can be attached to the rest of the molecule via a single bond. Examples of monocyclic cycloalkenyl groups include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl.

[0037] "Cycloalkylalkyl" refers to the formula -R c -Cycloalkyl radical, where R c It is an alkylene chain as described above.

[0038] "Cycloalkylalkoxy" refers to the compound with the formula -OR c-A cycloalkyl oxygen atom bonded free radical, wherein R c It is an alkylene chain as described above.

[0039] "Halogen" or "halogenated" refers to halogenated substituents such as bromine, chlorine, fluorine, and iodine substituents.

[0040] As used herein, the term "haloalkyl" or "haloalkane" refers to an alkyl radical as defined above, substituted with one or more halogen groups, such as trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, etc. In some embodiments, the alkyl portion of the fluoroalkyl radical may optionally be further substituted. Examples of halogen-substituted alkanes (“haloalkanes”) include halomethanes (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), dihalomethanes and trihalomethanes (e.g., chloroform, tribromomethane, trifluoromethane, triiodomethane), 1-haloethane, 2-haloethane, 1,2-dihaloethane, 1-halopropane, 2-halopropane, 3-halopropane, 1,2-dihalopropane, 1,3-dihalopropane, 2,3-dihalopropane, 1,2,3-trihalopropane, and any other suitable combination of alkanes (or substituted alkanes) and halogens (e.g., chlorine, bromine, fluorine, iodine, etc.). When the alkyl group is substituted by more than one halogen group, each halogen can be chosen independently, for example, 1-chloro,2-fluoroethane.

[0041] "Fluoroalkyl" refers to an alkyl radical as defined above that is substituted with one or more fluorine groups, such as trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, etc.

[0042] "Aminoalkyl" refers to an alkyl radical as defined above that is substituted by one or more amine radicals, such as propane-2-amine, butane-1,2-diamine, pentane-1,2,4-triamine, etc.

[0043] "Hydroxyalkyl" refers to an alkyl radical as defined above that is replaced by one or more hydroxyl radicals, such as propan-1-ol, butan-1,4-diol, pentan-1,2,4-triol, etc.

[0044] "Alkoxyalkyl" refers to an alkyl radical as defined above that is replaced by one or more alkoxy radicals, such as methoxymethane, 1,3-dimethoxybutane, 1-methoxypropane, 2-ethoxypentane, etc.

[0045] As used in this article, "cyanoalkyl" refers to an alkyl radical as defined above that is substituted by one or more cyano radicals, such as acetonitrile, 2-ethyl-3-methylbutadiene nitrile, butadiene nitrile, etc.

[0046] A "heterocycle" is a saturated, unsaturated, or aromatic ring containing one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycles include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. Each ring in a bicyclic heterocycle can be selected from saturated, unsaturated, and aromatic rings. Bicyclic heterocycles can be fused rings, bridged rings, or spirocyclic systems. In some cases, spirocyclic heterocycles have at least two molecular rings with only one common atom. Spirocyclic heterocycles include at least one heteroatom.

[0047] Heterocyclic alkenes are divalent heterocycles in which the rest of the molecule is attached to a free radical group.

[0048] "Heteroaryl" or "aromatic heterocycle" refers to a group derived from a heteroaromatic ring group containing one to eleven carbon atoms and at least one heteroatom, wherein each heteroatom can be selected from N, O, and S. As used herein, the heteroaromatic ring can be selected from monocyclic or bicyclic and fused-ring or bridged-ring systems, wherein at least one ring in the ring system is aromatic, that is, according to Hückel's theory, it contains a cyclic, delocalized (4n+2) ring. - Electronic system. The heteroatom in the heteroaryl radical may optionally be oxidized. One or more nitrogen atoms (if present) may optionally be quaternized. The heteroaryl group may be attached to the rest of the molecule by any atom of the heteroaryl group (where the valence state allows), such as the carbon or nitrogen atom of the heteroaryl group. Examples of heteroaryl groups include, but are not limited to, pyridine, pyrimidine, oxazole, furan, pyran, thiophene, isoxazole, benzimidazole, benzothiazole, and imidazopyridine.

[0049] "X-membered heteroaryl" refers to the number of atoms in the ring, i.e., X. For example, a 5-membered heteroaryl ring or a 5-membered aromatic heterocycle has 5 atoms in the ring, such as triazole, oxazole, thiophene, etc.

[0050] The term "unsaturated heterocycle" refers to a heterocycle having at least one degree of unsaturation and not containing an aromatic heterocycle. Examples of unsaturated heterocycles include dihydropyrrole, dihydrofuran, oxazoline, pyrazoline, and dihydropyridine. The heterocycle may optionally be substituted with one or more substituents, such as those described herein.

[0051] The term "substituted" refers to a portion having a substituent that replaces one or more hydrogen atoms on a carbon atom or a substituted heteroatom (e.g., NH in a structure). It should be understood that "substituted" or "replaced by" includes implicit limitations, namely that such substitution conforms to the permissible valence states of the substituted atom and the substituent, and that the substitution produces a stable compound, i.e., one that does not spontaneously undergo transformations such as by rearrangement, cyclization, elimination, etc. In some embodiments, "substituted" refers to a portion having a substituent that replaces two hydrogen atoms on the same carbon atom, such as replacing two hydrogen atoms on a single carbon atom with an oxo, imino, or thio group.

[0052] As used herein, the term "substituted" is intended to include all permissible substituents of an organic compound. In a broad sense, permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of the organic compound. For a suitable organic compound, permissible substituents may be one or more and may be the same or different. For the purposes of this disclosure, heteroatoms (such as nitrogen) may have hydrogen substituents and / or any permissible substituents of the organic compound described herein that satisfy the heteroatom valence state. In some embodiments, substituents may include any substituents described herein, such as: halogen, hydroxyl, oxo (=O), thio (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=N-NH2), -R b -OR a -R b -OC(O)-R a -R b -OC(O)-OR a -R b -OC(O)-N(R a )2、-R b -N(R a )2、-R b -C(O)R a -R b -C(O)OR a -R b -C(O)N(R a )2、-R b -OR c -C(O)N((R a )2、-R b -N(R a )C(O)OR a -R b -N(R a )C(O)R a -R b -N(R aS(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b -S(O) t OR a (where t is 1 or 2) and -R b -S(O) t N(R a )2 (where t is 1 or 2); and alkyl, alkenyl, alkynyl, aryl, aralkyl, areneyl, arynyl, cycloalkyl, cycloalkylalkyl and heterocyclic, any of which may optionally be substituted by: alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thio (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=N-NH2), -R b -OR a -R b -OC(O)-R a -R b -OC(O)-OR a -R b -OC(O)-N(R a )2、-R b -N(R a )2、-R b -C(O)R a -R b -C(O)OR a -R b -C(O)N(R a )2、-R b -OR c -C(O)N(R a )2、-R b -N(R a )C(O)OR a -R b -N(R a )C(O)R a -R b -N(R a S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b -S(O) t OR a(where t is 1 or 2) and R b -S(O) t N(R a )2 (where t is 1 or 2); where each R a Independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, wherein each R a (Where the valence state permits) it may optionally be substituted with the following: alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thio (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=N-NH2), -R b -OR a -R b -OC(O)-R a -R b -OC(O)-OR a -R b -OC(O)-N(R a )2、-R b -N(R a )2、-R b -C(O)R a -R b -C(O)OR a -R b -C(O)N(R a )2、-R b -OR c -C(O)N(R a )2、-R b -N(R a )C(O)OR a -R b -N(R a )C(O)R a -R b -N(R a S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b -S(O) t OR a (where t is 1 or 2) and -R b -S(O) t N(R a )2 (where t is 1 or 2); and where each R bIndependently selected from direct-chain or straight-chain or branched alkylene, alkenyl, or ynylene chains, and each R c It is a straight-chain or branched alkylene, alkenyl, or ynylene chain.

[0053] As used in this specification and claims, the singular forms “a,” “an,” and “the” include plural references unless the context clearly specifies otherwise.

[0054] The term "salt" or "pharmaceutically acceptable salt" refers to a salt derived from a variety of organic and inorganic counterions well known in the art. Pharmaceutically acceptable acid addition salts can be formed from inorganic and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, and p-toluenesulfonic acid. 、 Salicylic acid, etc. Pharmaceutically acceptable base addition salts can be formed from inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, etc. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines (including naturally occurring substituted amines), cyclic amines, basic ion exchange resins, etc., specifically such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. In some embodiments, pharmaceutically acceptable base addition salts are selected from ammonium, potassium, sodium, calcium, and magnesium salts.

[0055] As used in this article, the terms “parenteral administration” and “post-gastrointestinal administration” refer to administration methods other than intravenous and local administration, usually by injection, and including but not limited to intravenous, intramuscular, intra-arterial, intrathecal, intracapsular, intra-bursal, intraorbital, intracardiac, intradermal, intraperitoneal, tracheal, subcutaneous, subepidermal, intra-articular, subcapsular, subarachnoid, spinal, and intrasternal injections and infusions.

[0056] The phrase “pharmaceutically acceptable” as used in this article refers to compounds, materials, compositions, and / or dosage forms that, within reasonable medical judgment, are suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications, and that are commensurate with a reasonable benefit / risk ratio.

[0057] As used herein, the phrase “pharmaceutically acceptable excipient” or “pharmaceutically acceptable carrier” means a pharmaceutically acceptable material, composition, or medium, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. Each carrier must be “acceptable” in the sense that it is compatible with other components of the formulation and harmless to the patient. Some examples of materials that can be used as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose, and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose, and cellulose acetate; (4) tragacanth gum powder; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository wax; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and corn oil. Rice oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerol, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffers, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethanol; (20) phosphate buffer solution; and (21) other non-toxic compatible substances used in pharmaceutical preparations.

[0058] In some implementations, the term "prevention" or "avoidance" as used in relation to a disease or condition can refer to a compound reducing the occurrence of a disease or condition in a treated sample relative to an untreated control sample, or delaying the onset of one or more symptoms of a disease or condition or reducing its severity relative to an untreated control sample.

[0059] As used herein, the term “treatment” can include relieving, reducing or improving symptoms of a disease or condition, preventing other symptoms, improving or preventing the underlying cause of symptoms, suppressing a disease or condition, such as preventing the development of a disease or condition, alleviating a disease or condition, causing a disease or condition to subside, relieving the condition caused by a disease or condition, or preventing and / or therapeutically stopping the symptoms of a disease or condition.

[0060] The term "ligand" generally refers to a large molecular compound that recognizes and binds to an associated antigen or receptor on a target cell. Ligands can be used to deliver drugs to a target cell population that has bound the ligand, and include, but are not limited to, protein hormones, lectins, growth factors, antibodies, or other substances that can bind to cells, receptors, and / or antigen molecules. Ligands can be antibodies. Ligands can be antigen-binding fragments.

[0061] The term "targeting moiety" or "targeting unit" refers to a structure that has a selective affinity for a target molecule relative to other non-target molecules. The targeting moiety binds to the target molecule. Targeting units can include, for example, antibodies, peptides, ligands, receptors, or their binding portions. The target biomolecule can be a biological receptor or other cellular structure, such as a tumor antigen.

[0062] The term "antibody" refers to a complete antibody and any antigen-binding fragment (i.e., the "antigen-binding part") or single-chain variant. A complete antibody is a protein containing at least two heavy chains (H) and two light chains (L) linked together by disulfide bonds. Each heavy chain contains a heavy chain variable region (VH) and a heavy chain constant region, which contains three domains: CH1, CH2, and CH3. Each light chain contains a light chain variable region (VL or Vk) and a light chain constant region, which contains a single domain CL. The VH and VL regions can be further subdivided into hypervariable regions called complementarity-determining regions (CDRs), interspersed with more conserved framework regions (FRs). Each VH and VL contains three CDRs and four FRs, arranged in the following order from the amino terminus to the carboxyl terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The variable regions contain binding domains that interact with the antigen. The constant region can mediate the binding of antibodies to host tissues or factors, including various cells of the immune system (such as effector cells) and the first component (Clq) of the classical complement system. If the KD of antibody binding to antigen X is 1 × 10⁻⁶, then... -7 M or lower, 5×10 -8 M or lower, more preferably 1×10 -8 M or lower, more preferably 6×10 -9 M or lower, more preferably 3×10 -9 M or lower, or even more preferably 2×10 -9 If M is lower than a certain threshold, the antibody is said to "specifically bind" to antigen X. Antibodies can be chimeric antibodies, humanized antibodies, or preferably human antibodies. Heavy chain constant regions can be engineered to affect the type or degree of glycosylation, prolong antibody half-life, enhance or reduce interactions with effector cells or the complement system, or modulate other properties. Engineering can be accomplished by replacing, adding, or deleting one or more amino acids, or by replacing the domain with a domain from another immunoglobulin type, or a combination thereof.

[0063] The terms “antigen-binding fragment” and “antigen-binding part” (or simply “antibody part” or “antibody fragment”) in the context of antibodies refer to one or more antibody fragments that retain the ability to specifically bind to an antigen. Antigen-binding function of antibodies has been demonstrated to be achieved by fragments of full-length antibodies, such as (i) Fab fragments, monovalent fragments consisting of VL, VH, CL, and CH1 domains; (ii) F(ab')2 fragments, bivalent fragments consisting of two Fab fragments connected by disulfide bridges at the hinge region; (iii) Fab' fragments, which are essentially Fab fragments with partially hinge regions (see, for example, Abbas et al., Cellular and Molecular Immunology, 6th ed., Saunders Elsevier 2007); (iv) Fd fragments consisting of VH and CH1 domains; (v) Fv fragments consisting of VL and VH domains of a single antibody arm; (vi) dAb fragments (Ward et al., (1989) Nature 341:544-546), which consist of VH domains; (vii) separated complementarity-determining regions (CDRs); and (viii) nanobodies, heavy chain variable regions containing a single variable domain and two constant domains. Preferred antigen-binding fragments are Fab, F(ab')2, Fab', Fv, and Fd fragments. Furthermore, although the two domains VL and VH of the Fv fragment are encoded by different genes, they can be joined together via synthetic linkers using recombination methods, allowing them to be made into a single protein chain in which the VL and VH regions pair to form a monovalent molecule (called a single-chain Fv or scFv); see, for example, Bird et al. (1988) Science 242:423-426; and Huston et al. (1988) ProC. Natl. Acad. Sci. USA 85:5879-5883). Such single-chain antibodies are also encompassed within the term "antigen-binding portion" of the antibody.

[0064] The term "isolated antibody" means an antibody that is substantially free of other antibodies with different antigen specificities (e.g., an isolated antibody that specifically binds to antigen X is substantially free of antibodies that specifically bind to antigens other than antigen X). However, an isolated antibody that specifically binds to antigen X may be cross-reactive with other antigens, such as antigen X molecules from other species. In some embodiments, the isolated antibody specifically binds to human antigen X and does not cross-react with other (non-human) antigen X. Furthermore, the isolated antibody may be substantially free of other cellular material and / or chemicals.

[0065] The term "monoclonal antibody" or "monoclonal antibody composition" refers to an antibody molecule that consists of a single molecule and exhibits a single binding specificity and affinity for a specific epitope.

[0066] The term "human antibody" means an antibody with a variable region in which both the frame region and the CDR region (and a constant region, if present) are derived from human germline immunoglobulin sequences. Human antibodies may include late modifications, including natural or synthetic modifications. Human antibodies may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-directed mutagenesis in vitro or by somatic mutations in vivo). However, "human antibody" does not include antibodies in which a CDR sequence derived from another mammalian species (such as a mouse) is transplanted onto a human frame sequence.

[0067] The term "human monoclonal antibody" means an antibody that exhibits binding specificity and has a variable region in which both the framework region and the CDR region are derived from human germline immunoglobulin sequences. In one embodiment, the human monoclonal antibody is produced by a hybridoma comprising B cells obtained from a transgenic nonhuman animal (e.g., a transgenic mouse) having a genome containing human heavy chain transgenes and light chain transgenes fused with immortalized cells.

[0068] The term "epitope" refers to an amino acid typically bound by immunoglobulin VH / VL pairs, such as antibodies, their antigen-binding moieties, and other binding agents described herein. Other binding agents include non-antibody scaffolds. Epitopes can be formed on a polypeptide by consecutive amino acids or by discontinuous amino acids juxtaposed through the ternary folding of a protein. Epitopes formed by consecutive amino acids are generally retained upon exposure to denaturing solvents, while epitopes formed through ternary folding are generally lost upon treatment with denaturing solvents. Epitopes typically comprise at least three amino acids in a unique spatial conformation, and more typically at least five, about nine, or about eight to ten amino acids. An epitope defines the minimum binding site for antibodies, their antigen-binding moieties, and other binding agents, and thus represents a specific target for antibodies, their antigen-binding moieties, or other immunoglobulin-based binding agents. In the case of single-domain antibodies, the epitope represents a structural unit bound by separate, variable domains. Epitopes may include non-amino acid components, such as glycan structures.

[0069] The term "specific binding" refers to the binding of the molecules described herein (e.g., antibodies or their antigen-binding portions or non-antibody scaffolds) to a KD of 10. -5 M (10000 nM) or lower, such as 10 -6 M, 10 -7 M, 10 -8 M, 10 -9 M, 10 -10 M, 10 -11 M, 10 -12 The ability to target M or lower. Specific binding can be affected by factors such as the affinity and avidity of the antibody, antigen-binding moiety, or other binder, as well as the concentration of the target peptide.

[0070] The term “about” can mean + / -1% when used in conjunction with a percentage.

[0071] The term "cleavable unit" refers to a chemical group that can be cleaved by internal or external (preferably external) stimuli. Stimuli that trigger cleavage of a cleavable unit can be, for example, pH or temperature conditions, or the presence of an enzyme. Cleavage of a cleavable unit preferably triggers the self-sacrifice of the phenyl-containing linker in the compound of the present invention, releasing the active agent D.

[0072] The term "cuttable sugar unit" or "sugar-cuttable unit" can refer to the sugar moiety, preferably glucuronic acid or galactoside.

[0073] The term "peptide cleavable unit" can refer to a polypeptide, preferably a dipeptide or tripeptide.

[0074] The connectors, drug-connectors and conjugates disclosed herein In one aspect, this disclosure provides a drug-connector of formula (X): Formula (X) Or its pharmaceutically acceptable salt, wherein; R 40 Independently selected from hydrogen, Y and ; D is selected from the drug unit; n is selected from 0 and 1; m is selected from 0 and 1; Where at least n or m is 1; p is selected from 0 and 1; z is selected from 0 and 1; X is selected from CH and N; Y is -OT 1 and -NH-T 2 ; T 1 For sugar-cuttable units; T 2 It is a peptide cleavable unit; S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20(iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 3 Selected from the spacer region, wherein the spacer region is preferably phenylene, wherein S 3 To indicate whether something exists or does not exist; S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement; Where M 1 K 1 K 2 S 1 S 2 S 3 and S 4 The optional substituents on the surface are selected independently each time they appear: (i) Halogen, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 ) and -CN; (ii) C 1-10Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles; and (iii) C 3-10 A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group; M 1 These are groups that can react with ligands to form linker units; K 1 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; wherein when X is CH, D is eczema or MMAE, m is 1, n is 0, and K 1 It is polysarcosine, which contains 2-9 sarcosine or 13-30 sarcosine. K 2 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and Each R 30Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles.

[0075] In some implementations, equation (X) is represented as Formula (XI) or Formula (XII) Or its pharmaceutically acceptable salt.

[0076] In some implementations, equation (X) is represented as Formula (XIII) Or its pharmaceutically acceptable salt.

[0077] In some implementations, formula (X) or formula (XIII) is represented as Formula (I) Or its pharmaceutically acceptable salt.

[0078] In one respect, this disclosure provides a drug-connector of formula (I): Formula (I) Or its pharmaceutically acceptable salt, wherein; D is selected from the drug unit; n is selected from 0 and 1; m is selected from 0 and 1; Where at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is -OT 1 and -NH-T 2 ; T 1 For sugar-cuttable units; T 2 It is a peptide cleavable unit; S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 3 Selected from the spacer region, wherein the spacer region is preferably phenylene, wherein S 3 To indicate whether something exists or does not exist; S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement; Where M 1 K 1 K 2 S 1 S 2 S 3 and S 4 The optional substituents on the surface are selected independently each time they appear: (i) Halogen, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 ) and -CN; (ii) C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles; and (iii) C 3-10 A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group; M 1These are groups that can react with ligands to form linker units; K 1 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; wherein when X is CH, D is eczema or MMAE, m is 1, n is 0, and K 1 It is polysarcosine, which contains 2-9 sarcosine or 13-30 sarcosine. K 2 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and Each R 30 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles.

[0079] In one aspect, this disclosure provides a drug-connector of formula (Ia) or formula (Ib): Formula (Ia) Formula (Ib) Or its pharmaceutically acceptable salt, wherein; D is selected from the drug unit; n is selected from 0 and 1; m is selected from 0 and 1; Where at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is -OT 1 and -NH-T 2 ; T 1 For sugar-cuttable units; T 2 It is a peptide cleavable unit; S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20(iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 3 Selected from the spacer region, wherein the spacer region is preferably phenylene, wherein S 3 To indicate whether something exists or does not exist; S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement; Where M 1 K 1 K 2 S 1 S 2 S 3 and S 4 The optional substituents on the surface are selected independently each time they appear: (i) Halogen, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 ) and -CN; (ii) C 1-10Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles; and (iii) C 3-10 A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group; M 1 These are groups that can react with ligands to form linker units; K 1 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; wherein when X is CH, D is eczema or MMAE, m is 1, n is 0, and K 1 It is polysarcosine, which contains 2-9 sarcosine or 13-30 sarcosine. K 2 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and Each R 30Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles.

[0080] In one aspect, this disclosure provides conjugates of formula (XX): Formula (XX) Or its pharmaceutically acceptable salt, wherein; R 40 Independently selected from hydrogen, Y and ; D is selected from the drug unit; n is selected from 0 and 1; m is selected from 0 and 1; Where at least n or m is 1; p is selected from 0 and 1; z is selected from 0 and 1; X is selected from CH and N; Y is -OT 1 and -NH-T 2 ; T 1 For sugar-cuttable units; T 2 It is a peptide cleavable unit; S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 3Selected from the spacer region, wherein the spacer region is preferably phenylene, wherein S 3 To indicate whether something exists or does not exist; S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement; Where M 2 K 1 K 2 S 1 S 2 S 3 and S 4 The optional substituents on the surface are selected independently each time they appear: (i) Halogen, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 ) and -CN; (ii) C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles; and (iii) C 3-10 A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group; L represents the target unit; M 2 For connection units; K 1 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; wherein when X is CH, D is eczema or MMAE, m is 1, n is 0, and K 1 It is polysarcosine, which contains 2-9 sarcosine or 13-30 sarcosine. K 2 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and Each R 30 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles.

[0081] In one respect, this disclosure provides a conjugate of formula (A): Formula (A) Or its pharmaceutically acceptable salt, wherein; D is selected from the drug unit; n is selected from 0 and 1; m is selected from 0 and 1; Where at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is -OT 1 and -NH-T 2 ; T 1 For sugar-cuttable units; T 2 It is a peptide cleavable unit; S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 3 Selected from the spacer region, wherein the spacer region is preferably phenylene, wherein S 3 To indicate whether something exists or does not exist; S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R)20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement; Where M 2 K 1 K 2 S 1 S 2 S 3 and S 4 The optional substituents on the surface are selected independently each time they appear: (i) Halogen, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 ) and -CN; (ii) C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles; and (iii) C 3-10 A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group; L represents the target unit; M 2 For connection units; K 1 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; wherein when X is CH, D is eczema or MMAE, m is 1, n is 0, and K 1 It is polysarcosine, which contains 2-9 sarcosine or 13-30 sarcosine. K 2 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and Each R 30 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles.

[0082] In one aspect, this disclosure provides conjugates of formula (Aa) or formula (Ab): Formula (Aa), Formula (Ab) or Or its pharmaceutically acceptable salt, wherein; D is selected from the drug unit; n is selected from 0 and 1; m is selected from 0 and 1; Where at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is -OT 1 and -NH-T 2 ; T 1 For sugar-cuttable units; T 2 It is a peptide cleavable unit; S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 3 Selected from the spacer region, wherein the spacer region is preferably phenylene, wherein S 3 To indicate whether something exists or does not exist; S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement; Where M 2 K 1 K 2 S 1 S 2 S 3 and S 4 The optional substituents on the surface are selected independently each time they appear: (i) Halogen, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 ) and -CN; (ii) C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30-CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles; and (iii) C 3-10 A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group; L represents the target unit; M 2 For connection units; K 1 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; wherein when X is CH, D is eczema or MMAE, m is 1, n is 0, and K 1 It is polysarcosine, which contains 2-9 sarcosine or 13-30 sarcosine. K 2 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and Each R 30 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles.

[0083] In some implementations, n is 0 for formula (III) connectors or salts, or for formulas (I), (Ia), (Ib), (X), (XIII) drug-connectors or salts, or formulas (A), (Aa), (Ab), (XX), or (XXIII) conjugates. In some cases, n is 1.

[0084] In some implementations, p is 0 for formula (III) connectors or salts, or for formulas (I), (Ia), (Ib), (X), (XIII) drug-connectors or salts, or formulas (A), (Aa), (Ab), (XX), or (XXIII) conjugates. In some cases, p is 1.

[0085] In some implementations, equation (I) is represented as Formula (I-AA) Or its pharmaceutically acceptable salt.

[0086] In some implementations, formula (I) or formula (Ia) is represented as Formula (I-AAa) Or its pharmaceutically acceptable salt.

[0087] In some implementations, formula (I) or formula (Ib) is represented as Formula (I-AAb) Or its pharmaceutically acceptable salt.

[0088] In some implementations, equation (I) is represented as Formula (I-AB) Or its pharmaceutically acceptable salt.

[0089] In some implementations, formula (I) or formula (Ia) is represented as Formula (I-ABa) Or its pharmaceutically acceptable salt.

[0090] In some implementations, formula (I) or formula (Ib) is represented as Formula (I-ABb) Or its pharmaceutically acceptable salt.

[0091] In some implementations, equation (I) is represented as Formula (IA) Or its pharmaceutically acceptable salt.

[0092] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (I-AA), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (II-A), (II-B), (II-C), (II-D), (II-G) drug-conjugates or salts, or for formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), (A-3), or (A-4) conjugates or salts, S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, or -P(O)(R 20 )2-Replacement. In some cases, S 1 Selected from: (i) optional substitutions of C6-C 10 Alkylene, wherein C6-C 10 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 - or -C(O)- substitution. In some cases, S 1 It is an optionally substituted C1 alkylene group. In some cases, S 1 It is an optionally substituted C2 alkylene group. In some cases, S 1 It is an optionally substituted C3 alkylene group. In some cases, S 1 It is an optionally substituted C4 alkylene group. In some cases, S 1 It is an optionally substituted C5 alkylene group. In some cases, S 1 It is an optionally substituted C6 alkylene group. In some cases, S 1 It is an optionally substituted C7 alkylene group. In some cases, S 1 It is an optionally substituted C8 alkylene group. In some cases, S 1 It is an optionally substituted C9 alkylene group. In some cases, S 1 C is an optional replacement10 Alkylene. In some cases, S 1 C is an optional replacement 11 Alkylene. In some cases, S 1 C is an optional replacement 12 Alkylene. In some cases, S 1 C is an optional replacement 13 Alkylene. In some cases, S 1 C is an optional replacement 14 Alkylene. In some cases, S 1 C is an optional replacement 15 Alkylene. In some cases, S 1 C is an optional replacement 16 Alkylene. In some cases, S 1 C is an optional replacement 17 Alkylene. In some cases, S 1 C is an optional replacement 18 Alkylene. In some cases, S 1 C is an optional replacement 19 Alkylene. In some cases, S 1 C is an optional replacement 20 Alkylene. In some cases, S 1 One or more alkylene units of the alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、- S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement. In some cases, S 1 One or more alkylene units of the alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 - or -C(O)- substitution. In some cases, S 1 One or more alkylene units of the alkylene group are optionally and independently prefixed with -N(R) 20 - Replacement. In some cases, S 1 One or more alkylene units of the alkylene group are optionally and independently prefixed with -N(R) 20 C(O)-substitution. In some cases, S 1One or more alkylene units of the alkylene group are optionally and independently surrounded by -C(O)N(R) 20 - Replacement. In some cases, S 1 One or more alkylene units of the alkylene group are optionally and independently replaced by -C(O)-. In some cases, S 1 One or more alkylene units of the alkylene group are optionally and independently replaced by -O-. In some cases, if the alkylene unit of the alkylene group is replaced, the alkylene group may be referred to as the resulting alkylene group. In some cases, if S 1 If two or more alkylene units are replaced, the replaced alkylene units are not adjacent alkylene units. In some cases, if S 1 If two or more alkylene units are replaced, the adjacent alkylene units of the resulting alkylene group are not replaced. In some cases, if S 1 If two or more alkylene units are replaced, the resulting alkylene group does not have the heavy complex atoms of the adjacent alkylene units. In some cases, if S 1 If two or more alkylene units are replaced, the resulting alkylene unit will not have repeating identical heteroatoms in adjacent alkylene units. In some cases, if S 1 If two or more alkylene units are replaced, the resulting alkylene unit does not have -NN- or -OO-. In some cases, if S 1 If two or more alkylene units are replaced, the resulting alkylene unit is a stable alkylene. In some cases, if S 1 If two or more alkylene units are replaced, the resulting alkylene unit is an unreacted alkylene. In some cases, the resulting alkylene has only one heteroatom. In some cases, the resulting alkylene has only two heteroatoms, where the two heteroatoms are different from each other. In some cases, the resulting alkylene has only two heteroatoms, where the two heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only three heteroatoms, where the three heteroatoms are not adjacent to each other. In some cases, the alkylene has 0 substituted units. In some cases, the alkylene has one substituted unit. In some cases, the alkylene has two substituted units. In some cases, the alkylene has three substituted units. In some cases, the alkylene has four substituted units. In some cases, the alkylene has five substituted units. In some cases, the alkylene has six substituted units. In some cases, adjacent alkylene units of the alkylene are not replaced. In some cases, there are no adjacent alkylene units in the resulting alkylene that produce two or more adjacent heteroatoms (e.g., adjacent -N(R) units are not allowed). 20 S(O)2- and -N(R) 20 -, but allows a single -N(R)20 In some cases, if two heteroatoms originate from a single substituted alkylene unit, they may be present in the resulting alkylene. In some cases, the resulting alkylene has two heteroatoms, which originate from a single substituted alkylene unit. In some cases, if they are generated by a single substitution of an alkylene unit, the resulting alkylene has two heteroatoms. In some cases, S... 1 The optional substituents on the surface are independently selected each time they appear: (i) halogens, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 (ii) C and -CN; 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10Carbon rings and 3- to 10-membered heterocycles. In some cases, S 1 The optional substituents on the surface are independently selected each time they appear: (i) halogens, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 ) and -CN. In some cases, S 1 The optional substituents on the [substituent name] are independently selected each time they appear: halogen, -OR 30 -N(R) 30 2. =O and -CN. In some cases, S 1 The optional substituents on the surface are independently selected from O each time they appear.

[0093] In some implementations, for formulas (I), (X), and (XIII) drug-connectors or salts, X is CH; S 1 Selected from and ; S 2 Selected from ; S 3 It does not exist; M 1 for ; n is 0; m is 1; Y is selected from cleavable sugars and cleavable peptides (e.g., dipeptides). K 1 Selected from peptide units and oligosaccharides; and D is .

[0094] In some implementations, for formula (Ia), formula (Ib), formula (I-AAa), or formula (I-AAb) drug-connector or salt, X represents CH: S 1 Selected from and ; S 2 Selected from ; S 3 It does not exist; M 1 for ; n is 0; m is 1; Y is selected from cleavable sugars and cleavable peptides (e.g., dipeptides). K 1 Selected from peptide units and oligosaccharides; and D is .

[0095] In some implementations, for formulas (I), (X), and (XIII) drug-connectors or salts, X is CH; S 1 Selected from and ; S 2 for ; S 3 It does not exist; M 1 for ; n is 0; m is 1; Y is selected from and ; K 1 Selected from , , ; , and ;and D is .

[0096] In some implementations, for formulas (I), (X), and (XIII) drug-connectors or salts, X is CH; S 1 Selected from and ; S 2for ; S 3 It does not exist; M 1 for ; n is 0; m is 1; Y is selected from and ; K 1 Selected from , , , , , , , , , and ;and D is .

[0097] In some implementations, for formula (Ia), formula (Ib) drug-connector or salt, X is CH; S 1 Selected from and ; S 2 for ; S 3 It does not exist; M 1 for ; n is 0; m is 1; Y is selected from and ; K 1 Selected from , , , , , , , , , and ;and D is .

[0098] In some implementations, for formula (I-AAa) or formula (I-Aab) drug-connector or salt, S 1 Selected from and ; S 2 for ; S 3 It does not exist; M 1 for ; n is 0; m is 1; Y is selected from and ; K 1 Selected from , , , , , , , , , and ;and D is .

[0099] In some implementations, for formulas (I), (X), and (XIII) drug-connectors or salts, X is N; S 1 Selected from and ; S 2 for ; S 3 It does not exist; M 1 for ; n is 0; m is 1; Y is selected from and ; K 1 Selected from , , , , , and ;and D is .

[0100] In some implementations, for formulas (I), (X), and (XIII) drug-connectors or salts, X is N; S 1 Selected from and ; S 2 for ; S 3 It does not exist; M 1 for ; n is 0; m is 1; Y is selected from and ; K 1 Selected from , , , , , , , , , , and ;and D is .

[0101] In some implementations, for formula (Ia), formula (Ib), formula (I-AAa), or formula (I-AAb) drug-connector or salt, X is N; S1 Selected from and ; S 2 for ; S 3 It does not exist; M 1 for ; n is 0; m is 1; Y is selected from and ; K 1 Selected from , , , , , , , , , , and ;and D is .

[0102] In some implementations, for formulas (I), (X), and (XIII) drug-connectors or salts, X is CH; S 1 for ; S 2 for ; S 3 It does not exist; M 1 for ; n is 1; m is 0; p is 1; S 4 Selected from and ; Y is selected from cleavable sugars and cleavable peptides (e.g., dipeptides). K 2 Selected from peptide units and oligosaccharides; and D is .

[0103] In some implementations, for formula (Ia), formula (Ib), formula (I-AAa), or formula (I-AAb) drug-connector or salt, X is CH; S 1 for ; S 2 for ; S 3 It does not exist; M 1 for ; n is 1; m is 0; p is 1; S 4 Selected from and ; Y is selected from cleavable sugars and cleavable peptides (e.g., dipeptides). K 2 Selected from peptide units and oligosaccharides; and D is .

[0104] In some implementations, for formulas (I), (X), and (XIII) drug-connectors or salts, X is CH; S 1 for (Preferred) ); S 2 for (For example, preferred) ); S 3 It does not exist; M 1 for ; n is 1; m is 0; p is 1; S 4 Selected from and ; Y is selected from and ; K 2 It is a choice , , , ; , and ;and D is .

[0105] In some implementations, for formulas (I), (X), and (XIII) drug-connectors or salts, X is CH; S 1 for ; S 2 for ; S 3 It does not exist; M 1 for ; n is 1; m is 0; p is 1; S 4 Selected from and ; Y is selected from and ; K 2 Selected from , , , , , , , , , , and ;and D is .

[0106] In some implementations, for formula (Ia), formula (Ib), formula (I-AAa), or formula (I-AAb) drug-connector or salt, X is CH; S 1 for ; S 2 for ; S3 It does not exist; M 1 for ; n is 1; m is 0; p is 1; S 4 Selected from and ; Y is selected from and ; K 2 It is a choice , , , , , , , , , , and ;and D is .

[0107] In some embodiments, for formula (III) connectors or salts, or for formulas (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (II-C), (I-CA), or (II-D), (X), (XI), (XII), or (XIII) drug-conjugates or salts, or for formulas (A), (Aa), (Ab), (A-1), (A-3), (A-4), (XX), (XXI), (XXII), or (XXIII) conjugates or salts, S 1 It is a branched alkylene group.

[0108] In some implementations, for formula (III) connectors or salts, or for formulas (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (II-A), (II-B), (II-C), (II-CA), (II-D), (X), (XI), (XII), and (XIII) drug-conjugates or salts, or for formulas (A), (Aa), (Ab), (A-1), (XX), (XXI), (XXII), or (XXIII) conjugates or salts, S 1 Selected from .

[0109] In some implementations, for formula (III) connectors or salts, or for formulas (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (II-A), (II-B), (II-C), (II-D), (X), (XI), (XII), and (XIII) drug-conjugates or salts, or for formulas (A), (Aa), (Ab), (A-1), (XX), (XXI), (XXII), or (XXIII) conjugates or salts, in some cases, S 1 Represented as .

[0110] In some implementations, for formula (I) drug-connector or salt, S 1 -K 1 Represented as In some cases, Represented as .

[0111] In some implementations, for formula (III) connectors or salts, or for formulas (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (II-A), (II-B), (II-C), (II-CA), (II-D), (II-G), (X), (XI), (XII), and (XIII) drug-connectors or salts, or for formulas (A), (Aa), (Ab), (A-1), (A-3), (A-4), (XX), (XXI), (XXII), and (XXIII) conjugates or salts, S 2 Selected from: (i) optional substitutions of C8-C 12 Alkylene, wherein C8-C 12One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 -, -O-, and -C(O)- substitutions. In some cases, S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement. In some cases, S 2 Selected from: (i) optional substitutions of C6-C 10 Alkylene, wherein C6-C 10 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 - or -C(O)- substitution. In some cases, S 2 It is an optionally substituted C1 alkylene group. In some cases, S 2 It is an optionally substituted C2 alkylene group. In some cases, S 2 It is an optionally substituted C3 alkylene group. In some cases, S 2 It is an optionally substituted C4 alkylene group. In some cases, S 2 It is an optionally substituted C5 alkylene group. In some cases, S 2 It is an optionally substituted C6 alkylene group. In some cases, S 2 It is an optionally substituted C7 alkylene group. In some cases, S 2 It is an optionally substituted C8 alkylene group. In some cases, S 2 It is an optionally substituted C9 alkylene group. In some cases, S 2 C is an optional replacement 10 Alkylene. In some cases, S 2 C is an optional replacement 11 Alkylene. In some cases, S 2 C is an optional replacement 12 Alkylene. In some cases, S2 C is an optional replacement 13 Alkylene. In some cases, S 2 C is an optional replacement 14 Alkylene. In some cases, S 2 C is an optional replacement 15 Alkylene. In some cases, S 2 C is an optional replacement 16 Alkylene. In some cases, S 2 C is an optional replacement 17 Alkylene. In some cases, S 2 C is an optional replacement 18 Alkylene. In some cases, S 2 C is an optional replacement 19 Alkylene. In some cases, S 2 C is an optional replacement 20 Alkylene. In some cases, S 2 One or more alkylene units of the alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、- S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement. In some cases, S 2 One or more alkylene units of the alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 - or -C(O)- substitution. In some cases, S 2 One or more alkylene units of the alkylene group are optionally and independently prefixed with -N(R) 20 - Replacement. In some cases, S 2 One or more alkylene units of the alkylene group are optionally and independently prefixed with -N(R) 20 C(O)-substitution. In some cases, S 2 One or more alkylene units of the alkylene group are optionally and independently surrounded by -C(O)N(R) 20 - Replacement. In some cases, S 2 One or more alkylene units of the alkylene group are optionally and independently replaced by -C(O)-. In some cases, S 2One or more alkylene units of the alkylene group are optionally and independently replaced by -O-. In some cases, if the alkylene unit of the alkylene group is replaced, the alkylene group may be referred to as the resulting alkylene group. In some cases, if S 2 If two or more alkylene units are replaced, the replaced alkylene units are not adjacent alkylene units. In some cases, if S 2 If two or more alkylene units are replaced, the adjacent alkylene units of the resulting alkylene group are not replaced. In some cases, if S 2 If two or more alkylene units are replaced, the resulting alkylene group does not have the heavy complex atoms of the adjacent alkylene units. In some cases, if S 2 If two or more alkylene units are replaced, the resulting alkylene unit will not have repeating identical heteroatoms in adjacent alkylene units. In some cases, if S 2 If two or more alkylene units are replaced, the resulting alkylene unit does not have -NN- or -OO-. In some cases, if S 2 If two or more alkylene units are replaced, the resulting alkylene unit is a stable alkylene. In some cases, if S 2 When two or more alkylene units are replaced, the resulting alkylene unit is an unreacted alkylene. In some cases, the resulting alkylene has only one heteroatom. In some cases, the resulting alkylene has only two heteroatoms, where the two heteroatoms are different from each other. In some cases, the resulting alkylene has only two heteroatoms, where the two heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only three heteroatoms, where the three heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only four heteroatoms, where the four heteroatoms are not adjacent to each other. In some cases, the alkylene has 0 substituted units. In some cases, the alkylene has one substituted unit. In some cases, the alkylene has two substituted units. In some cases, the alkylene has three substituted units. In some cases, the alkylene has four substituted units. In some cases, the alkylene has five substituted units. In some cases, S 2 The optional substituents on the surface are independently selected each time they appear: (i) halogens, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30-S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 (ii) C and -CN; 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles. In some cases, S 2 The optional substituents on the surface are independently selected each time they appear: (i) halogens, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 ) and -CN. In some cases, S 2The optional substituents on the [substituent name] are independently selected each time they appear: halogen, -OR 30 -N(R) 30 2. =O and -CN. In some cases, S 2 The optional substituents on the alkylene group are independently selected from :=O each time they appear. In some cases, if two heteroatoms originate from a single substituted alkylene unit, they may be present in the resulting alkylene group. In some cases, the resulting alkylene group has two heteroatoms, which originate from a single substituted alkylene unit. In some cases, if they are generated by a single substitution of an alkylene unit, the resulting alkylene group has two heteroatoms.

[0112] In some implementations, for formula (III) connectors or salts, or for formulas (I), (Ia), (I-AAa), (Ib), (I-AAb), (II-A), (II-B), (II-C), (II-D), (II-G), (X), (XI), (XII), (XIII) drug-conjugates or salts, or for formulas (A), (Aa), (Ab), (A-1), (A-3), (A-4), (XX), (XXI), (XXII), (XXIII) conjugates or salts, S 2 It is a linear alkylene group.

[0113] In some implementations, for formula (III) connectors or salts, or for formulas (I), (Ia), (I-AAa), (Ib), (I-AAb), (II-A), (II-B), (X), (XI), (XII), and (XIII) drug-conjugates or salts, or for formulas (A), (Aa), (Ab), (A-1), (A-3), (A-4), (XX), (XXI), (XXII), and (XXIII) conjugates or salts, S 2 Represented as In some cases, S 2 Represented as In some cases, S 2 Represented as .

[0114] In some implementations, formula (I) or formula (IA) is represented as Formula (IB) Or its pharmaceutically acceptable salt.

[0115] In some implementations, X is CH for formula (III) connector or salt, or for formula (I), formula (Ia), formula (Ib), formula (IA) or formula (IB), formula (X), formula (XIII) drug-connector or salt, or for formula (A), formula (Aa), formula (Ab), formula (A-1), formula (A-2), formula (XX) or formula (XXIII) conjugate or salt.

[0116] In some implementations, X is N for formula (III) connectors or salts, or for formula (I), formula (Ia), formula (Ib), formula (IA), formula (IB), formula (X), formula (XIII) drug-connectors or salts, or for formula (A), formula (Aa), formula (Ab), formula (A-1), formula (A-2), formula (XX), or formula (XXIII) conjugates or salts.

[0117] In some implementations, equation (I) is represented as Formula (II-A) Or its pharmaceutically acceptable salt.

[0118] In some implementations, equation (I) is represented as Formula (II-B) Or its pharmaceutically acceptable salt.

[0119] In some implementations, equation (X) is represented as Formula (II-G) Or its pharmaceutically acceptable salt.

[0120] In some implementations, equation (I) is represented as Formula (II-C) Or its pharmaceutically acceptable salt.

[0121] In some implementations, equation (I) is represented as Equation (II-D) Or its pharmaceutically acceptable salt.

[0122] In some implementations, equation (I) is represented as Formula (II-CA) Or its pharmaceutically acceptable salt.

[0123] In some implementations, for formula (III) connectors or salts, or for formulas (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (II-A), (II-B), (II-C), (II-CA), (II-D), (II-G), (X), (XI), (XII), and (XIII) drug-connectors or salts, or for formulas (A), (Aa), (Ab), (A-1), (A-3), (A-4), (XX), (XXI), (XXII), and (XXIII) conjugates or salts, S 1 Selected from: (i) optional substituted C4-C 10 Alkylene, wherein C4-C 10 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )- or -C(O)- substitution.

[0124] In some embodiments, for formula (III) connectors or salts, or for formulas (I), (Ia), (I-AAa), (Ib), (I-AAb), (II-A), (II-B) drug-conjugates or salts, or for formulas (A), (Aa), (Ab), (A-1), (A-3), or (A-4) conjugates or salts, S 1 Selected from: (i) optionally substituted C1-C3 alkylene groups, wherein one or more alkylene units of the C1-C3 alkylene group are optionally and independently converted to -N(R 20 - Replacement. In some cases, S 1 Selected from: (i) optionally substituted C1-C2 alkylene groups, wherein one or more alkylene units of the C1-C2 alkylene group are optionally and independently converted to -N(R 20 - Replacement. In some cases, S 1 Selected from: (i) optionally substituted C2-C3 alkylene groups, wherein one or more alkylene units of the C2-C3 alkylene group are optionally and independently converted to -N(R 20 - Replacement. In some cases, S 1 Selected from In some cases, S 1 Represented as .

[0125] In some embodiments, for formula (III) connectors or salts, or for formulas (I), (Ia), (I-AAa), (Ib), (I-AAb), (II-A), (II-B) drug-conjugates or salts, or for formulas (A), (Aa), (Ab), (A-3), or (A-4) conjugates or salts, S 1 Selected from: In some cases, S 1 Represented as .

[0126] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (II-A), (II-B), (II-C), (II-CA), (II-D), (II-G) drug-conjugates or salts, or for formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), (A-3), or (A-4) conjugates or salts, S 2 Selected from: (i) optional substitutions of C8-C 12 Alkylene, wherein C8-C 12 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 -, -O-, and -C(O)- substitutions. In some cases, S 2 Selected from In some cases, S 2 Represented as .

[0127] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (II-A), (II-B), (II-C), (II-CA), (II-D), (II-G) drug-conjugates or salts, or for formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), (A-3), or (A-4) conjugates or salts, S 2 Selected from: (i) optional substitutions of C8-C12 Alkylene, wherein C8-C 12 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 -, -O-, and -C(O)- substitutions. In some cases, S 2 Selected from and In some cases, S 2 Represented as In some cases, S 2 Represented as .

[0128] In some embodiments, for formula (III) connectors or salts, or for formulas (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (II-A), (II-B), (II-C), (II-CA), (II-D) drug-conjugates or salts, or for formulas (A), (Aa), (Ab), (A-1), (A-3), or (A-4) conjugates or salts, S 2 It is a linear alkylene group.

[0129] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (I-AA), (I-AB), (II-A), (II-B), (II-C), (II-CA), (II-D), (II-G) drug-conjugates or salts, or for formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), (A-3), or (A-4) conjugates or salts, S 2 Represented as In some cases, S 2 Represented as .

[0130] In some embodiments, for formula (III) connectors or salts, or for formulas (I), (Ia), (I-AAa), (Ib), (I-AAb), (II-A), (II-B) drug-conjugates or salts, or for formulas (A), (Aa), (Ab), (A-3), or (A-4) conjugates or salts, S 1 -S 2Represented as .

[0131] In some embodiments, for formula (III) connectors or salts, or for formulas (I), (Ia), (I-AAa), (Ib), (I-AAb), (II-A), (II-B) drug-conjugates or salts, or for formulas (A), (Aa), (Ab), (A-3), or (A-4) conjugates or salts, S 1 -S 2 -M 1 Represented as S 3 It does not exist.

[0132] In some embodiments, for formula (III) connectors or salts, or for formula (I), formula (I-AA), formula (IA), formula (Ia), formula (I-AAa), formula (Ib), formula (I-AAb), formula (IB), formula (II-A), formula (II-B), formula (II-C), formula (II-D) drug-conjugates or salts, or for formula (A), formula (Aa), formula (Ab), formula (A-1), formula (A-2), formula (A-3), or formula (A-4) conjugates or salts, S 3 It exists and is a phenylene oxide.

[0133] In some implementations, for formula (III) connectors or salts, or for formulas (I), (Ia), (I-AAa), (Ib), (I-AAb), (I-AA), (IA), (IB), (II-A), (II-B), (II-C) drug-conjugates or salts, or for formulas (A), (Aa), (Ab), (A-1), (A-2), (A-3), or (A-4) conjugates or salts, S 3 It does not exist.

[0134] In some implementations, formula (I) drug-connector or salt is represented as Equation (II-E). In some cases, p is 1.

[0135] In some implementations, formula (I) drug-connector or salt is represented as Equation (II-F). In some cases, p is 1.

[0136] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XIII), (I), (I-AA), (I-CA), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-A), (II-B), (II-C), (II-CA), (II-D), (II-E), (II-F) drug-connectors or salts, or for formulas (XX), (XXIII), (A), (Aa), (Ab), (A-1), (A-2), (A-3), (A-4), (A-5), or (A-6) conjugates or salts, T 1 The cleavable unit of sugar includes sugar. In some cases, the sugar is glucuronic acid. In some cases, the sugar is selected from fructose, galactose, glucose, xylose, and ribose. In some cases, the sugar is a monosaccharide. In some cases, the sugar is a disaccharide. In some cases, T... 1 for .

[0137] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XIII), (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-A), (II-B), (II-C), (II-CA), (II-D), (II-E), (II-F) drug-connectors or salts, or for formulas (XX), (XXIII), (A), (Aa), (Ab), (A-1), (A-2), (A-3), (A-4), (A-5), or (A-6) conjugates or salts, Y is .

[0138] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XIII), (I), (Ia), (I-AAa), (Ib), (I-AAb), (I-AA), (I-AB), (IA), (IB), (II-A), (II-B), (II-C), (II-CA), (II-D), (II-E), (II-F) drug-connectors or salts, or for formulas (XX), (XXIII), (A), (Aa), (Ab), (A-1), (A-2), (A-3), (A-4), (A-5), or (A-6) conjugates or salts, T 2The peptide unit comprises one or more amino acids selected from the following: alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-alanine. In some cases, T 2 The peptide unit comprises one or more amino acids selected from the following: alanine, arginine, asparagine, aspartic acid, glutamine, glycine, lysine, methionine, phenylalanine, proline, serine, valine, citrulline, and β-alanine. In some cases, T... 2 The peptide units include dipeptides or tripeptides. In some cases, T... 2 The peptide unit includes a dipeptide. In some cases, the dipeptide is selected from Val-Cit, Val-Ala, and Phe-Lys.

[0139] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XIII), (I), (Ia), (I-AAa), (Ib), (I-AAb), (I-AA), (I-AB), (IA), (IB), (II-A), (II-B), (II-C), (II-A), (II-D), (II-E), (II-F) drug-connectors or salts, or for formulas (XX), (XXIII), (A), (Aa), (Ab), (A-1), (A-2), (A-3), (A-4), (A-5), or (A-6) conjugates or salts, T 2 The peptide unit includes a capping moiety. In some cases, the capping moiety is capable of reacting with an amine of the peptide to form an amide, carbamate, or sulfonamide. In some cases, the capping moiety is generated from the reaction with an amine to form an amide, carbamate, or sulfonamide. In some cases, the capping moiety is generated from the reaction with an amine to form an amide. In some cases, the capping moiety is the portion that caps the end of the peptide / amino acid. In some cases, the capping moiety is an acyl moiety. In some cases, the capping moiety is... R* is selected from C 1-6 Alkyl group. In some cases, the end cap is... In some cases, Y is R* is selected from C 1-6 Alkyl group. In some cases, Y is... .

[0140] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-C), (II-CA), (II-D) drug-conjugates or salts, or for formulas (A), (Aa), (Ab), (A-1), or (A-2) conjugates or salts, K 1 Not polysarcosine. In some cases, K 1 This excludes adjacent creatine residues. In some cases, when K... 1 When sarcosine is included, at least one other amino acid is present. In some cases, when a peptide unit includes sarcosine, at least one other amino acid is present.

[0141] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-C), (II-CA), (II-D) drug-conjugates or salts, or for formulas (A), (Aa), (Ab), (A-1), or (A-2) conjugates or salts, K 1 This includes PASylation. In some cases, PASylation consists of peptides containing proline, alanine, and serine. In others, it consists of peptides composed only of proline, alanine, and serine. In still others, K... 1 This includes PAS formulations with fewer than PAS100 amino acids. For example, PAS100 refers to a peptide with 100 amino acids, where the amino acids are selected from proline, alanine, and serine. In some cases, K... 1 This includes PASification with less than PAS50. In some cases, K 1 This includes PASification of less than PAS25. In some cases, K 1 This includes PASification beyond PAS5. In some cases, K 1 This includes PASification beyond PAS9. In some cases, K... 1 This includes PASification beyond PAS15. In some cases, K 1 This includes PASification from PAS5 to PAS25. In some cases, K... 1 This includes PASification from PAS10 to PAS20. In some cases, K... 1 This includes the PASification of PAS10. In some cases, K1 This includes the PASification of PAS20. In some cases, K 1 This includes PAS-linking β-alanine to a drug-linker. In some cases, PAS-linking is used to prolong plasma half-life. In some cases, PAS-linking is used to increase solubility. In some cases, PAS-linking is used to increase solubility without generating secondary structures. In some cases, PAS-linking is... In some cases, PAS is converted to .

[0142] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-C), (II-CA), (II-D) drug-conjugates or salts, or for formulas (A), (Aa), (Ab), (A-1), or (A-2) conjugates or salts, K 1 Not polysarcosine. In some cases, K 1 Including adjacent creatine. In some cases, when K 1 When creatine is included, at least one other amino acid is present. In some cases, when K... 1 When an adjacent sarcosine is included, at least one other amino acid is present. In some cases, when the peptide unit includes sarcosine, at least one other amino acid is present. In some cases, when the peptide unit includes an adjacent sarcosine, at least one other amino acid is present. In some cases, K 1 It includes glycine and two adjacent sarcosines. In some cases, K... 1 It includes glycine and three adjacent sarcosines. In some cases, K... 1 It includes glycine and four adjacent sarcosines. In some cases, K... 1 It is a peptide unit selected from glycine and two adjacent sarcosine residues. In some cases, K... 1 It is a peptide unit selected from glycine and three adjacent sarcosine residues. In some cases, K... 1 It is a peptide unit selected from glycine and four adjacent sarcosine residues. In some cases, K... 1 It includes 2 glycines and 8 sarcosines. In some cases, K... 1 It includes 3 glycines and 8 sarcosines. In some cases, K... 1 It includes 4 glycines and 7 sarcosines. In some cases, K... 1 It includes 3 glycines and 7 sarcosines. In some cases, K... 1It includes 3 glycines and 6 sarcosines. In some cases, K... 1 It includes 3 glycines and 5 creatines. In some cases, K... 1 It includes 3 glycines and 4 sarcosines. In some cases, K... 1 It includes 3 glycines and 3 sarcosines. In some cases, K... 1 It includes 3 glycines and 9 sarcosines. In some cases, K... 1 It includes 3 glycines and 10 creatines. In some cases, K... 1 It includes 5 glycines and 5 creatines. In some cases, K... 1 It includes 4 glycines and 4 sarcosines. In some cases, K... 1 It includes 4 glycines and 5 sarcosines. In some cases, K... 1 It includes 5 glycines and 4 creatines. In some cases, K... 1 It has up to 9 sarcosine residues. In some cases, K... 1 It has up to 8 sarcosine residues. In some cases, K... 1 It has up to 7 sarcosine residues. In some cases, K... 1 It has up to 6 sarcosine residues. In some cases, K... 1 It has up to 5 sarcosine residues. In some cases, K... 1 It has up to 4 sarcosine residues. In some cases, K... 1 It has up to 3 sarcosine residues. In some cases, K... 1 It has at most 2 sarcosine residues. In some cases, K... 1 It has at most one sarcosine residue. In some cases, K... 1 It has up to 9 glycine residues. In some cases, K... 1 It has up to 8 glycine residues. In some cases, K... 1 It has up to 7 glycine residues. In some cases, K... 1 It has up to 6 glycine residues. In some cases, K... 1 It contains up to 5 glycine residues. In some cases, K... 1 It contains up to four glycine residues. In some cases, K... 1 It contains at most 3 glycine residues. In some cases, K... 1 It contains at most two glycine residues. In some cases, K... 1 It contains at most one glycine.

[0143] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (Ia), (I-AAa), (Ib), (I-AAb), (I-AA), (I-AB), (IA), (IB), (II-C), (II-CA), (II-D) drug-connectors or salts, or for formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), or (A-2) conjugates or salts, each K 1 Selected from peptide units. In some cases, K 1 The peptide unit has 1 to 50 amino acids. In some cases, K 1 The peptide unit has 1 to 20 amino acids. In some cases, K 1 The peptide unit has 1 to 10 amino acids. In some cases, K 1 The peptide unit has 2 to 50 amino acids. In some cases, K 1 The peptide unit has 2 to 40 amino acids. In some cases, K 1 The peptide unit has 2 to 30 amino acids. In some cases, K 1 The peptide unit has 2 to 20 amino acids. In some cases, K 1 The peptide unit has 2 to 10 amino acids. In some cases, K 1 The peptide unit has 5 to 10 amino acids. In some cases, K 1 The peptide unit has at least one amino acid. In some cases, K 1 The peptide unit has one amino acid. In some cases, K 1 The peptide unit has at least two amino acids. In some cases, K 1 The peptide unit has at least 5 amino acids. In some cases, K 1 The peptide unit has at least 8 amino acids. In some cases, K 1 The peptide unit has at least 10 amino acids. In some cases, K 1 The peptide unit has at most 10 amino acids. In some cases, K 1 The peptide unit has 10 amino acids. In some cases, K 1 The peptide unit has at least 12 amino acids. In some cases, K 1 The peptide unit has at most 12 amino acids. In some cases, K 1 The peptide unit has at least 20 amino acids. In some cases, K 1 The peptide unit has up to 20 amino acids. In some cases, K1 The peptide unit has 20 amino acids. In some cases, K 1 The peptide unit has up to 30 amino acids. In some cases, K 1 The peptide unit has at least 30 amino acids. In some cases, K 1 The amino acids are selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-alanine. In some cases, K... 1 The amino acids are selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-alanine. In some cases, K... 1 The amino acids are selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-alanine. In some cases, K... 1 The amino acids are selected from glycine, sarcosine, proline, serine, alanine, and β-alanine. In some cases, K... 1 The amino acids are selected from glycine, proline, serine, alanine, and β-alanine. In some cases, K... 1 The amino acids are selected from proline, serine, alanine, and β-alanine. In some cases, K... 1 The amino acids in it include at least one glycine and at least one other amino acid. In some cases, K 1 The amino acids in it include at least one glycine and at least one sarcosine. In some cases, K 1 The amino acids include at least one glycine and at least one other amino acid selected from proline, serine, alanine, and β-alanine. In some cases, K 1 The amino acids are selected from glycine, proline, serine, alanine, and β-alanine. In some cases, K... 1 Includes at least one glycine. In some cases, K 1 Includes at least one proline. In some cases, K 1 Includes at least one serine. In some cases, K 1 Includes at least one alanine. In some cases, K 1 It includes at least one β-alanine.

[0144] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (Ia), (I-AAa), (Ib), (I-AAb), (I-AA), (I-AB), (IA), (IB), (II-C), (II-CA), (II-D) drug-connectors or salts, or for formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), or (A-2) conjugates or salts, each K 1 Selected from peptide units. In some cases, K 1 The peptide unit has 1 to 50 amino acids. In some cases, K 1 The peptide unit has 1 to 20 amino acids. In some cases, K 1 The peptide unit has 1 to 10 amino acids. In some cases, K 1 The peptide unit has 2 to 50 amino acids. In some cases, K 1 The peptide unit has 2 to 40 amino acids. In some cases, K 1 The peptide unit has 2 to 30 amino acids. In some cases, K 1 The peptide unit has 2 to 20 amino acids. In some cases, K 1 The peptide unit has 2 to 10 amino acids. In some cases, K 1 The peptide unit has 5 to 10 amino acids. In some cases, K 1 The peptide unit has at least one amino acid. In some cases, K 1 The peptide unit has one amino acid. In some cases, K 1 The peptide unit has at least two amino acids. In some cases, K 1 The peptide unit has at least 5 amino acids. In some cases, K 1 The peptide unit has at least 8 amino acids. In some cases, K 1 The peptide unit has at least 10 amino acids. In some cases, K 1 The peptide unit has at most 10 amino acids. In some cases, K 1 The peptide unit has 10 amino acids. In some cases, K 1 The peptide unit has at least 12 amino acids. In some cases, K 1 The peptide unit has at most 12 amino acids. In some cases, K 1 The peptide unit has at least 20 amino acids. In some cases, K 1 The peptide unit has up to 20 amino acids. In some cases, K1 The peptide unit has 20 amino acids. In some cases, K 1 The peptide unit has up to 30 amino acids. In some cases, K 1 The peptide unit has at least 30 amino acids. In some cases, K 1 It is a peptide unit selected from glycine and two adjacent sarcosine residues. In some cases, K... 1 It is a peptide unit selected from glycine and three adjacent sarcosine residues. In some cases, K... 1 It is a peptide unit selected from glycine and four adjacent sarcosines. In some cases, when the peptide unit includes adjacent sarcosines, at least one other amino acid is present. In some cases, K... 1 It includes glycine and two adjacent sarcosines. In some cases, K... 1 It includes glycine and three adjacent sarcosines. In some cases, K... 1 It includes glycine and four adjacent sarcosines. In some cases, K... 1 It is a peptide unit selected from glycine and two adjacent sarcosine residues. In some cases, K... 1 It is a peptide unit selected from glycine and three adjacent sarcosine residues. In some cases, K... 1 It is a peptide unit selected from glycine and four adjacent sarcosine residues. In some cases, K... 1 It includes 2 glycines and 8 sarcosines. In some cases, K... 1 It includes 3 glycines and 8 sarcosines. In some cases, K... 1 It includes 4 glycines and 7 sarcosines. In some cases, K... 1 It includes 3 glycines and 7 sarcosines. In some cases, K... 1 It includes 3 glycines and 6 sarcosines. In some cases, K... 1 It includes 3 glycines and 5 creatines. In some cases, K... 1 It includes 3 glycines and 4 sarcosines. In some cases, K... 1 It includes 3 glycines and 3 sarcosines. In some cases, K... 1 It includes 3 glycines and 9 sarcosines. In some cases, K... 1 It includes 3 glycines and 10 creatines. In some cases, K... 1 It includes 5 glycines and 5 creatines. In some cases, K... 1 It includes 4 glycines and 4 sarcosines. In some cases, K... 1 It includes 4 glycines and 5 sarcosines. In some cases, K... 1 It includes 5 glycines and 4 creatines. In some cases, K... 1It has up to 9 sarcosine residues. In some cases, K... 1 It has up to 8 sarcosine residues. In some cases, K... 1 It has up to 7 sarcosine residues. In some cases, K... 1 It has up to 6 sarcosine residues. In some cases, K... 1 It has up to 5 sarcosine residues. In some cases, K... 1 It has up to 4 sarcosine residues. In some cases, K... 1 It has up to 3 sarcosine residues. In some cases, K... 1 It has at most 2 sarcosine residues. In some cases, K... 1 It has at most one sarcosine residue. In some cases, K... 1 It has up to 9 glycine residues. In some cases, K... 1 It has up to 8 glycine residues. In some cases, K... 1 It has up to 7 glycine residues. In some cases, K... 1 It has up to 6 glycine residues. In some cases, K... 1 It contains up to 5 glycine residues. In some cases, K... 1 It contains up to four glycine residues. In some cases, K... 1 It contains at most 3 glycine residues. In some cases, K... 1 It contains at most two glycine residues. In some cases, K... 1 It contains at most one glycine. In some cases, K 1 The amino acids are selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-alanine. In some cases, K... 1 The amino acids are selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-alanine. In some cases, K... 1 The amino acids are selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-alanine. In some cases, K... 1 The amino acids are selected from glycine, sarcosine, proline, serine, alanine, and β-alanine. In some cases, K... 1The amino acids are selected from glycine, proline, serine, alanine, and β-alanine. In some cases, K... 1 The amino acids are selected from proline, serine, alanine, and β-alanine. In some cases, K... 1 The amino acids in it include at least one glycine and at least one other amino acid. In some cases, K 1 The amino acids in it include at least one glycine and at least one sarcosine. In some cases, K 1 The amino acids include at least one glycine and at least one other amino acid selected from proline, serine, alanine, and β-alanine. In some cases, K 1 The amino acids are selected from glycine, proline, serine, alanine, and β-alanine. In some cases, K... 1 Includes at least one glycine. In some cases, K 1 Includes at least one proline. In some cases, K 1 Includes at least one serine. In some cases, K 1 Includes at least one alanine. In some cases, K 1 It contains at least one β-alanine.

[0145] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-C), (II-CA), (II-D) drug-conjugates or salts, or for formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), or (A-2) conjugates or salts, K 1 The peptide unit has a terminal unit. In some cases, K 1 Selected from , , , , , , The end unit is represented as R. 6 And each j is selected from 1 to 30. In some cases, K 1 Selected from , , , , , The end unit is represented as R. 6 And each j is selected from 1 to 30. In some cases, j is 1. In some cases, j is 3. In some cases, j is 5. In some cases, j is 10. In some cases, j is 20. In some cases, R 6 Selected from -OR 7 and -NHR 7 , where R 7 Selected from hydrogen; C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles. In some cases, R 6 Selected from -OH, -NH2 and In some cases, R 6 It is -OH. In some cases, R 6 It is -NH2. In some cases, R 6 for .

[0146] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-C), (II-CA), (II-D) drug-conjugates or salts, or for formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), or (A-2) conjugates or salts, K 1 Selected from , , , , and In some cases, K 1 Selected from , , , and In some cases, K 1 Selected from In some cases, K 1 Selected from In some cases, K 1 Selected from In some cases, K 1 Selected from In some cases, K 1 Selected from .

[0147] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-C), (II-CA), (II-D) drug-conjugates or salts, or for formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), or (A-2) conjugates or salts, K 1 The peptide unit has a terminal unit. In some cases, K 1 Selected from , , , , , , The end unit is represented as R. 6 And each j is selected from 1 to 30. In some cases, K 1 Selected from , , , , , The end unit is represented as R. 6 And each j is selected from 1 to 30. In some cases, j is 1. In some cases, j is 3. In some cases, j is 5. In some cases, j is 10. In some cases, j is 20. In some cases, R 6 Selected from -OR 7 and -NHR 7 , where R 7 Selected from hydrogen; C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles. In some cases, R 6 Selected from -OH, -NH2 and In some cases, R 6 It is -OH. In some cases, R 6 It is -NH2. In some cases, R 6 for .

[0148] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-C), (II-CA), (II-D) drug-conjugates or salts, or for formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), or (A-2) conjugates or salts, K 1 Selected from , , , , , , , , , and In some cases, K 1 Selected from , , , , , and In some cases, K 1 Selected from In some cases, K 1 Selected from In some cases, K 1 Selected from In some cases, K 1 Selected from In some cases, K 1 Selected from In some cases, K 1 Selected from In some cases, K 1 Selected from , , , , , , and In some cases, K 1 Selected from and In some cases, K 1 Selected from and In some cases, K 1 Selected from , , and In some cases, K 1 Selected from In some cases, K 1 Selected from In some cases, K 1 Selected from In some cases, K 1 Selected from In some cases, K 1 Selected from .

[0149] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-C), (II-CA), (II-D) drug-conjugates or salts, or for formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), or (A-2) conjugates or salts, K 1 Selected from peptide units, wherein the peptide unit has a terminal -NH2. In some cases, K 1 Selected from peptide units, wherein the peptide unit has a terminal -OH. In some cases, K 1 Selected from peptides, wherein the peptide has a terminal -NH2. In some cases, K 1 Selected from peptides, wherein the peptide has a terminal -OH.

[0150] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-C), (II-CA), (II-D) drug-conjugates or salts, or for formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), or (A-2) conjugates or salts, K1 The peptide unit has a terminal unit. In some cases, K 1 Selected from , , , , , , , , The end unit is represented as R. 6 And each j is selected from 1 to 30. In some cases, K 1 Selected from , , , , , , , The end unit is represented as R. 6 And each j is selected from 1 to 30. In some cases, K 1 Selected from , , , In some cases, K 1 Selected from , , In some cases, K 1 Selected from , , The end unit is represented as R. 6 And each j is selected from 1 to 30. In some cases, j is 1. In some cases, j is 3. In some cases, j is 5. In some cases, j is 10. In some cases, j is 20. In some cases, R 6 Selected from -OR 7 and -NHR 7 , where R 7 Selected from hydrogen; C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30-C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles. In some cases, R 6 Selected from -OH, -NH2 and In some cases, R 6 It is -OH. In some cases, R 6 It is -NH2. In some cases, R 6 for .

[0151] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (I-AA), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-C), (II-D) drug-conjugates or salts, or for formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), or (A-2) conjugates or salts, each K 1 Selected from: Oligosaccharides. In some cases, each K 1 Selected from: , where k is selected from 2 to 10. In some cases, each K 1 Selected from: Where k is selected from 2 to 10. In some cases, k is 2. In some cases, k is 3. In some cases, k is 4. In some cases, k is 5. In some cases, k is 6. In some cases, each K 1 Selected from: In some cases, each K 1 Selected from: .

[0152] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-C), (II-CA), (II-D) drug-conjugates or salts, or for formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), or (A-2) conjugates or salts, S 1 Represented as In some cases, S 1 for And K 1 It is an oligosaccharide. In some cases, S 1 for And K 1 Selected from and In some cases, S 1 for And K 1 for In some cases, S 1 for And K 1 for In some cases, K 1 for .

[0153] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XIII), (I), (Ia), (Ib), (II-A), (II-B), (II-E), and (II-F) drug-conjugates or salts, or for formulas (XX), (XXIII), (A), (Aa), (Ab), (A-3), (A-4), (A-5), or (A-6) conjugates or salts, K 2 Selected from peptide units. In some cases, peptide units are residues. In some cases, K 2 The peptide unit has 1 to 50 amino acids. In some cases, K 2 The peptide unit has 1 to 20 amino acids. In some cases, K 2 The peptide unit has 1 to 10 amino acids. In some cases, K 2 The peptide unit has 2 to 50 amino acids. In some cases, K 2 The peptide unit has 2 to 40 amino acids. In some cases, K 2The peptide unit has 2 to 30 amino acids. In some cases, K 2 The peptide unit has 2 to 20 amino acids. In some cases, K 2 The peptide unit has 2 to 10 amino acids. In some cases, K 2 The peptide unit has 5 to 10 amino acids. In some cases, K 2 The peptide unit has at least one amino acid. In some cases, K 2 The peptide unit has one amino acid. In some cases, K 2 The peptide unit has at least two amino acids. In some cases, K 2 The peptide unit has at least 5 amino acids. In some cases, K 2 The peptide unit has at least 8 amino acids. In some cases, K 2 The peptide unit has at least 10 amino acids. In some cases, K 2 The peptide unit has at most 10 amino acids. In some cases, K 2 The peptide unit has 10 amino acids. In some cases, K 2 The peptide unit has at least 12 amino acids. In some cases, K 2 The peptide unit has at most 12 amino acids. In some cases, K 2 The peptide unit has at least 20 amino acids. In some cases, K 2 The peptide unit has up to 20 amino acids. In some cases, K 2 The peptide unit has 20 amino acids. In some cases, K 2 The peptide unit has up to 30 amino acids. In some cases, K 2 The peptide unit has at least 30 amino acids. In some cases, K 2 The amino acids are selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-alanine. In some cases, K... 2 The amino acids are selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-alanine. In some cases, K... 2The amino acids are selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-alanine. In some cases, K... 2 The amino acids are selected from glycine, sarcosine, proline, serine, alanine, and β-alanine. In some cases, K... 2 The amino acids are selected from sarcosine, proline, serine, alanine, and β-alanine. In some cases, K... 2 The amino acids are selected from glycine, proline, serine, alanine, and β-alanine. In some cases, K... 2 The amino acids are selected from glycine, proline, serine, alanine, and β-alanine. In some cases, K... 2 Includes at least one glycine. In some cases, K 2 Includes at least one proline. In some cases, K 2 Includes at least one serine. In some cases, K 2 Includes at least one alanine. In some cases, K 2 Includes at least one β-alanine. In some cases, K 2 It's polysarcosine. In some cases, K... 2 It is a polysarcosine with ten repeating sarcosine units. In some cases, K 2 The amino acids include at least one glycine and at least one amino acid. In some cases, K 2 The amino acids include at least one glycine and at least one amino acid selected from sarcosine, proline, serine, alanine, and β-alanine.

[0154] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (I-AA), (I-AB), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-C), (II-CA), (II-D) drug-conjugates or salts, or for formulas (A), (Aa), (Ab), (A-1), or (A-2) conjugates or salts, K 2 Not polysarcosine. In some cases, K 2 Including adjacent creatine. In some cases, when K 2 When creatine is included, at least one other amino acid is present. In some cases, when K... 2When an adjacent sarcosine is included, at least one other amino acid is present. In some cases, when the peptide unit includes sarcosine, at least one other amino acid is present. In some cases, when the peptide unit includes an adjacent sarcosine, at least one other amino acid is present. In some cases, K 2 It includes glycine and two adjacent sarcosines. In some cases, K... 2 It includes glycine and three adjacent sarcosines. In some cases, K... 2 It includes glycine and four adjacent sarcosines. In some cases, K... 2 It is a peptide unit selected from glycine and two adjacent sarcosine residues. In some cases, K... 2 It is a peptide unit selected from glycine and three adjacent sarcosine residues. In some cases, K... 2 It is a peptide unit selected from glycine and four adjacent sarcosine residues. In some cases, K... 2 It includes 2 glycines and 8 sarcosines. In some cases, K... 2 It includes 3 glycines and 8 sarcosines. In some cases, K... 2 It includes 4 glycines and 7 sarcosines. In some cases, K... 2 It includes 3 glycines and 7 sarcosines. In some cases, K... 2 It includes 3 glycines and 6 sarcosines. In some cases, K... 2 It includes 3 glycines and 5 creatines. In some cases, K... 2 It includes 3 glycines and 4 sarcosines. In some cases, K... 2 It includes 3 glycines and 3 sarcosines. In some cases, K... 2 It includes 3 glycines and 9 sarcosines. In some cases, K... 2 It includes 3 glycines and 10 creatines. In some cases, K... 2 It includes 5 glycines and 5 creatines. In some cases, K... 2 It includes 4 glycines and 4 sarcosines. In some cases, K... 2 It includes 4 glycines and 5 sarcosines. In some cases, K... 2 It includes 5 glycines and 4 creatines. In some cases, K... 2 It has up to 9 sarcosine residues. In some cases, K... 2 It has up to 8 sarcosine residues. In some cases, K... 2 It has up to 7 sarcosine residues. In some cases, K... 2 It has up to 6 sarcosine residues. In some cases, K... 2 It has up to 5 sarcosine residues. In some cases, K... 2 It has up to 4 sarcosine residues. In some cases, K...2 It has up to 3 sarcosine residues. In some cases, K... 2 It has at most 2 sarcosine residues. In some cases, K... 2 It has at most one sarcosine residue. In some cases, K... 2 It has up to 9 glycine residues. In some cases, K... 2 It has up to 8 glycine residues. In some cases, K... 2 It has up to 7 glycine residues. In some cases, K... 2 It has up to 6 glycine residues. In some cases, K... 2 It contains up to 5 glycine residues. In some cases, K... 2 It contains up to four glycine residues. In some cases, K... 2 It contains at most 3 glycine residues. In some cases, K... 2 It contains at most two glycine residues. In some cases, K... 2 It contains at most one glycine.

[0155] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XIII), (I), (Ia), (Ib), (II-A), (II-B), (II-E), and (II-F) drug-conjugates or salts, or for formulas (XX), (XXIII), (A), (Aa), (Ab), (A-3), (A-4), (A-5), or (A-6) conjugates or salts, K 2 The peptide unit has a terminal unit. In some cases, K 2 Selected from , , , , , , , The end unit is represented as R. 6 And each j is selected from 1 to 30. In some cases, K 2 Selected from , , , , , The end unit is represented as R. 6 And each j is selected from 1 to 30. In some cases, j is 1. In some cases, j is 3. In some cases, j is 5. In some cases, j is 10. In some cases, j is 20. In some cases, R 6 Selected from -OR 7 and -NHR 7, where R 7 Selected from hydrogen; C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles. In some cases, R 6 Selected from -OH, -NH2 and In some cases, R 6 It is -OH. In some cases, R 6 It is -NH2. In some cases, R 6 for .

[0156] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XIII), (I), (Ia), (Ib), (II-A), (II-B), (II-E), and (II-F) drug-conjugates or salts, or for formulas (XX), (XXIII), (A), (Aa), (Ab), (A-3), (A-4), (A-5), or (A-6) conjugates or salts, K 2 The peptide unit has a terminal unit. In some cases, K 2 Selected from , , , , , , , , , The end unit is represented as R. 6And each j is selected from 1 to 30. In some cases, K 2 Selected from , , , , , , , The end unit is represented as R. 6 And each j is selected from 1 to 30. In some cases, j is 1. In some cases, j is 3. In some cases, j is 5. In some cases, j is 10. In some cases, j is 20. In some cases, R 6 Selected from -OR 7 and -NHR 7 , where R 7 Selected from hydrogen; C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles. In some cases, R 6 Selected from -OH, -NH2 and In some cases, R 6 It is -OH. In some cases, R 6 It is -NH2. In some cases, R 6 for .

[0157] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XIII), (I), (Ia), (Ib), (II-A), (II-B), (II-E), and (II-F) drug-conjugates or salts, or for formulas (XX), (XXIII), (A), (Aa), (Ab), (A-3), (A-4), (A-5), or (A-6) conjugates or salts, K 2 Selected from , , , , , , and In some cases, K 2 Selected from , , , , , and In some cases, K 2 Selected from In some cases, K 2 Selected from In some cases, K 2 Selected from In some cases, K 2 Selected from In some cases, K 2 Selected from .

[0158] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XIII), (I), (Ia), (Ib), (II-A), (II-B), (II-E), and (II-F) drug-conjugates or salts, or for formulas (XX), (XXIII), (A), (Aa), (Ab), (A-3), (A-4), (A-5), or (A-6) conjugates or salts, K 2 Selected from , , , , , , , , , , and In some cases, K 2 Selected from , , , , , , , , , , , and In some cases, K 2 Selected from In some cases, K 2 Selected from In some cases, K 2 Selected from In some cases, K 2 Selected from In some cases, K 2 Selected from In some cases, K 2 Selected from , , , , , , and .

[0159] In some cases, K 2 Selected from and In some cases, K 2 Selected from and In some cases, K 2 Selected from , , and .

[0160] In some embodiments, for formula (III) connectors or salts, or for formulas (X), (XIII), (I), (Ia), (Ib), (II-A), (II-B), (II-E), and (II-F) drug-conjugates or salts, or for formulas (X), (XIII), (A), (Aa), (Ab), (A-3), (A-4), (A-5), or (A-6) conjugates or salts, each K 2 Selected from: Oligosaccharides. In some cases, each K 2 Selected from Where k is selected from 2 to 10. In some cases, k is 2. In some cases, k is 3. In some cases, k is 4. In some cases, k is 5. In some cases, k is 6. In some cases, each K 2 Selected from In some cases, each K 2 Selected from .

[0161] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (I-AA), (II-A), (II-B), (II-C), or (II-D) drug-connectors or salts, M 1 A group that can react with a target unit to form a linker unit. In some cases, a group that can react with a target unit to form a linker unit refers to any chemical part that reacts with the covalently bound target unit (e.g., antibody, ligand, antigen-binding fragment). In some cases, it can react with a thiol group present on the target unit. In some cases, it can react with a thiol group present on an antibody or its antigen-binding fragment. In some cases, it can react with a thiol group present on a ligand. In some cases, the chemical moiety reactive to covalently bound ligands includes: carboxylic acids; primary amines; secondary amines; tertiary amines; hydroxyl groups; halogens; activated esters such as N-hydroxysuccinimide esters, perfluorinated esters, nitrobenzene esters, azidotriazoles and benzotriazole activated esters, acylureas; alkynyl groups; alkenyl groups; azides; isocyanates; isothiocyanates; aldehydes; mercapto-reactive moieties such as maleimides, halogenated maleimides, halogenated acetyl groups, pyridyl disulfides; thiols; acrylates; methanesulfonates; toluenesulfonates; trifluoromethanesulfonates; hydroxylamines; chlorosulfonyl groups; borate-B(OR')2 derivatives, where R' is a hydrogen or alkyl group. In some cases, M 1 Selected from maleimide, halogen, COOH, azides Activated Groups, , OH, SH, activated disulfide groups, NH2, and -ONH2. In some cases, M 1 It is maleimide. In some cases, M 1 It is a halogen. In some cases, M 1 For COOH. In some cases, M 1 for In some cases, M 1 It is an azide. In some cases, M 1 for In some cases, M 1 Activation Groups are selected from , and In some cases, M 1 for In some cases, M 1 for In some cases, M 1 for In some cases, M 1 for In some cases, M 1 It is OH. In some cases, M 1 For SH. In some cases, M 1 The activated dithio group is selected from and In some cases, M 1 for In some cases, M 1 It is NH2. In some cases, M 1 For -ONH2. In some cases, M 1 Suitable for click reactions (e.g., cyclic alkynes, azides). In some cases, M 1 for .

[0162] In some implementations, for drug-connectors or salts of formulas (X), (XI), (XII), (XIII), (I), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (I-AA), (I-AB), (IB), (II-A), (II-B), (II-C), (II-CA), (II-D), (II-E), (II-F), and (II-G), or for conjugates or salts of formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), (A-2), (A-3), (A-4), (A-5), or (A-6), K 1 It is a hydrophilic spacer region. In some cases, K 1 Selected from polyethylene glycol units, cyclodextrin units, polyamides, hydrophilic peptides, polysaccharides, and dendritic macromolecules. In some cases, K 1 Selected from polyamides, hydrophilic peptides, and polysaccharides. In some cases, K 1 Selected from hydrophilic peptides and polysaccharides. In some cases, K 1 Selected from hydrophilic peptides. In some cases, K1 Selected from polysaccharides. In some cases, condition K... 1 These are substituents that enhance half-life. In some cases, substituents that enhance half-life increase the half-life of the drug. In other cases, substituents that enhance half-life increase the half-life of the conjugate.

[0163] In some implementations, for drug-connectors or salts of formulas (X), (XIII), (I), (Ia), (Ib), (II-A), (II-B), (II-E), and (II-F), or for conjugates or salts of formulas (XX), (XXIII), (A), (Aa), (Ab), (A-3), (A-4), (A-5), and (A-6), K 2 It is a hydrophilic spacer region. In some cases, K 2 Selected from polyethylene glycol units, cyclodextrin units, polyamides, hydrophilic peptides, polysaccharides, and dendritic macromolecules. In some cases, K 2 Selected from polyamides, hydrophilic peptides, and polysaccharides. In some cases, K 2 Selected from hydrophilic peptides and polysaccharides. In some cases, K 2 Selected from hydrophilic peptides. In some cases, K 2 Selected from polysaccharides. In some cases, condition K... 2 These are substituents that enhance half-life. In some cases, substituents that enhance half-life increase the half-life of the drug. In some cases, substituents that enhance half-life increase the half-life of the conjugate. In some cases, p is 1.

[0164] In some implementations, for drug-connectors or salts of formulas (X), (XIII), (I), (Ia), (Ib), (II-A), (II-B), (II-E), and (II-F), or for conjugates or salts of formulas (XX), (XXIII), (A), (Aa), (Ab), (A-3), (A-4), (A-5), and (A-6), K 2 This includes PAS formulation. In some cases, PAS formulation is a peptide that includes proline, alanine, and serine. In other cases, PAS formulation is a peptide composed only of proline, alanine, and serine. In some cases, K... 2 This includes PAS formulations with fewer than PAS100 amino acids. For example, PAS100 refers to a peptide with 100 amino acids, where the amino acids are selected from proline, alanine, and serine. In some cases, K... 2 This includes PASification with less than PAS50. In some cases, K 2 This includes PASification of less than PAS25. In some cases, K 2This includes PASification beyond PAS5. In some cases, K 2 This includes PASification beyond PAS9. In some cases, K... 2 This includes PASification beyond PAS15. In some cases, K 2 This includes PASification from PAS5 to PAS25. In some cases, K... 2 This includes PASification from PAS10 to PAS20. In some cases, K... 2 This includes the PASification of PAS10. In some cases, K 2 This includes the PASification of PAS20. In some cases, K 2 This includes PAS-linking β-alanine to a drug-linker. In some cases, PAS-linking is used to prolong plasma half-life. In some cases, PAS-linking is used to increase solubility. In some cases, PAS-linking is used to increase solubility without generating secondary structures. In some cases, PAS-linking is... In some cases, PAS is converted to .

[0165] In some embodiments, for drug-connectors or salts of formulas (X), (XI), (XII), (XIII), (I), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), (II-G), or for conjugates or salts of formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), (A-2), (A-3), (A-4), (A-5), or (A-6), D is a pharmaceutical unit. In some cases, D includes a spacer region. In some cases, the spacer region is a divalent portion that covalently attaches the drug to the connector. In some cases, the spacer region is a divalent portion that covalently attaches the drug to the remainder of the molecule. In some cases, D does not include a spacer. In some cases, the spacer can be selected from -C1-C. 10 Alkylene-, -C1-C 10 Heteroalkylene-, -C3-C8 carbocyclic-, -O-(C1-C8 alkyl)-, -arylene-, -C1-C 10 alkylene-arylene-, -arylene-C1-C 10 Alkylene-, -C1-C 10 Alkylene-(C3-C8 carbide ring)-, -(C3-C8 carbide ring)-C1-C 10 Alkylene-, -C3-C8 heterocyclic-, -C1-C 10Alkylene-(C3-C8 heterocyclic)-, -(C3-C8 heterocyclic)-C1-C 10 Alkylene-, -C1-C 10 Alkylene -C(=O)-, -C1-C 10 Heteroalkylene-C(=O)-, -C3-C8 carbocyclic-C(=O)-, -O-(C1-C8 alkyl)-C(=O)-, -arylene-C(=O)-, -C1-C 10 alkylene-arylene-C(=O)-, -arylene-C1-C 10 Alkylene -C(=O)-, -C1-C 10 Alkylene -(C3-C8 carbide ring)-C(=O)-, -(C3-C8 carbide ring)-C1-C 10 Alkylene -C(=O)-, -C3-C8 heterocyclic -C(=O)-, -C1-C 10 Alkylene-(C3-C8 heterocyclic)-C(=O)-, -(C3-C8 heterocyclic)-C1-C 10 Alkylene -C(=O)-, -C1-C 10 Alkylene -NH-, -C1-C 10 Heteroalkylene-NH-, -C3-C8 carbocyclic-NH-, -O-(C1-C8 alkyl)-NH-, -arylene-NH-, -C1-C 10 Alkylene-arylene-NH-, -arylene-C1-C 10 Alkylene -NH-, -C1-C 10 Alkylene-(C3-C8 carbide ring)-NH-, -(C3-C8 carbide ring)-C1-C 10 Alkylene -NH-, -C3-C8 heterocyclic -NH-, -C1-C 10 Alkylene-(C3-C8 heterocyclic)-NH-, -(C3-C8 heterocyclic)-C1-C 10 Alkylene -NH-, -C1-C 10 Alkylene-S-, -C1-C 10 Heteroalkylene-S-, -C3-C8 carbocyclic-S-, -O-(C1-C8 alkyl)-)-S-, -arylene-S-, -C1-C 10 alkylene-arylene-S-, -arylene-C1-C 10 Alkylene -S-, -C1-C 10 Alkylene -(C3-C8 carbide ring)-S-, -(C3-C8 carbide ring)-C1-C 10 Alkylene-S-, -C3-C8 heterocyclic-S-, -C1-C 10 Alkylene-(C3-C8 heterocyclic)-S-, -(C3-C8 heterocyclic)-C1-C10 Alkylene -S-, -C1-C 10 Alkylene-OC(=O)-, -C3-C8 carbocyclic-OC(=O)-, -O-(C1-C8 alkyl)-OC(=O)-, -arylene-OC(=O)-, -C1-C 10 Alkylene-arylene-OC(=O)-, -arylene-C1-C 10 Alkylene -OC(=O)-, -C1-C 10 Alkylene -(C3-C8 carbide ring)-OC(=O)-, -(C3-C8 carbide ring)-C1-C 10 Alkylene -OC(=O)-, -C3-C8 heterocyclic -OC(=O)-, -C1-C 10 Alkylene-(C3-C8 heterocyclic)-OC(=O)- and -(C3-C8 heterocyclic)-C1-C 10 Alkylene -OC(=O)-. In some cases, the spacer region can be selected from -C1-C. 10 Alkylene- and -C1-C 10 Alkylene-NH-. In some cases, the pharmaceutical unit is simply the drug itself.

[0166] In some embodiments, for drug-connectors or salts of formulas (X), (XI), (XII), (XIII), (I), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), (II-G), or for conjugates or salts of formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), (A-2), (A-3), (A-4), (A-5), or (A-6), D is selected from drug units. In some cases, the drug unit comprises a drug. In some cases, the drug unit is a drug. In some cases, the drug unit is a drug and a spacer region. In some cases, D is selected from a drug. In some cases, D is selected from cytotoxic agents, immunomodulators, nucleic acids, growth inhibitors, PROTACs, toxins, radioactive isotopes, and chelating ligands. In some cases, D is selected from cytotoxic agents and immunomodulators. In some cases, D is selected from eczema and monomethylaurestatin E (MMAE). In some cases, D is camptothecin. In some cases, D is eczema. In some cases, D is... In some cases, D is SN-38. In some cases, D is selected from MMAF and MMAE. In some cases, the cytotoxic agent is selected from aurestatin, maytansinoid, camptothecin, duocarmycin, and calicheamicin. In some cases, the cytotoxic agent is an agent that has cytotoxic effects on cells. In some cases, the cytotoxic agent includes, for example, tubulin disruptors, topoisomerase inhibitors, DNA minor groove binding agents, and DNA alkylating agents. In some cases, the tubulin disruptors include, for example, aurestatin, dolastatin, tubulolysin, colchicine, vinca alkaloids, taxane, cryptophycin, maytansin, hemiasterlin, and other tubulin disruptors. In some cases, aurestatin is a derivative of the natural product dolastatin 10. In some cases, auristatin is selected from MMAE (N-methylvaline-valine-dolaisoleuine-dolaproine-norephedrine), MMAF (N-methylvaline-valine-dolaisoleuine-dolaproine-phenylalanine), and AFP. In some cases, the cytotoxic agent may be a topoisomerase inhibitor. In some cases, the drug is an immunomodulator, such as a TLR7 and / or TLR8 agonist. In some cases, the immunomodulator is a STING agonist. In some cases, the drug is a radioactive atom. In some cases, the drug is a proteolytic-targeting chimera (PROTAC). In some cases, the drug is selected from eczema, MMAE, MMAF, pyruvicin, SN-38, and dxd. In some cases, the drug is selected from MMAE, MMAF, pyruvicin, SN-38, and dxd. In some cases, the drug is... In some cases, medication is... In some cases, medication is... In some cases, medication is... In some cases, medication is... .

[0167] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (I-AA), (IB), (II-A), (II-B), (II-C) drug-conjugates or salts, or formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), (A-2), (A-3), or (A-4) conjugates or salts, S 3 Selected from the spacer region. In some cases, the spacer region is the divalent portion of two components of a covalently bound conjugate or drug-linker. In some cases, S 3 It exists. In some cases, S 3 The spacer region is not present. In some cases, the spacer region is selected from: alkylene, heteroalkylene (an alkylene group having one or more alkylene units replaced by at least one heteroatom selected from Si, N, O, and S with an appropriate valence); polyethers such as polyalkylene glycols, and typically polyethylene glycol; one or more natural or non-natural amino acids such as glycine, alanine, proline, valine, N-methylglycine; C3-C8 heterocycles; C3-C8 carbocyclic rings; arylene groups and any combination thereof. In some cases, the spacer region is a divalent linear alkylene group. In some cases, the spacer region may be selected from -C1-C... 10 Alkylene-, -C1-C 10 Heteroalkylene-, -C3-C8 carbocyclic-, -O-(C1-C8 alkyl)-, -arylene-, -C1-C 10 alkylene-arylene-, -arylene-C1-C 10 Alkylene-, -C1-C 10 Alkylene-(C3-C8 carbide ring)-, -(C3-C8 carbide ring)-C1-C 10 Alkylene-, -C3-C8 heterocyclic-, -C1-C 10 Alkylene-(C3-C8 heterocyclic)-, -(C3-C8 heterocyclic)-C1-C 10 Alkylene-, -C1-C 10 Alkylene -C(=O)-, -C1-C 10 Heteroalkylene-C(=O)-, -C3-C8 carbocyclic-C(=O)-, -O-(C1-C8 alkyl)-C(=O)-, -arylene-C(=O)-, -C1-C 10 alkylene-arylene-C(=O)-, -arylene-C1-C 10 Alkylene -C(=O)-, -C1-C 10Alkylene -(C3-C8 carbide ring)-C(=O)-, -(C3-C8 carbide ring)-C1-C 10 Alkylene -C(=O)-, -C3-C8 heterocyclic -C(=O)-, -C1-C 10 Alkylene-(C3-C8 heterocyclic)-C(=O)-, -(C3-C8 heterocyclic)-C1-C 10 Alkylene -C(=O)-, -C1-C 10 Alkylene -NH-, -C1-C 10 Heteroalkylene-NH-, -C3-C8 carbocyclic-NH-, -O-(C1-C8 alkyl)-NH-, -arylene-NH-, -C1-C 10 Alkylene-arylene-NH-, -arylene-C1-C 10 Alkylene -NH-, -C1-C 10 Alkylene-(C3-C8 carbide ring)-NH-, -(C3-C8 carbide ring)-C1-C 10 Alkylene -NH-, -C3-C8 heterocyclic -NH-, -C1-C 10 Alkylene-(C3-C8 heterocyclic)-NH-, -(C3-C8 heterocyclic)-C1-C 10 Alkylene -NH-, -C1-C 10 Alkylene-S-, -C1-C 10 Heteroalkylene-S-, -C3-C8 carbocyclic-S-, -O-(C1-C8 alkyl)-)-S-, -arylene-S-, -C1-C 10 alkylene-arylene-S-, -arylene-C1-C 10 Alkylene -S-, -C1-C 10 Alkylene-(C3-C8 carbide ring)-S-, -(C3-C8 carbide ring)-C1-C 10 Alkylene-S-, -C3-C8 heterocyclic-S-, -C1-C 10 Alkylene-(C3-C8 heterocyclic)-S-, -(C3-C8 heterocyclic)-C1-C 10 Alkylene -S-, -C1-C 10 Alkylene-OC(=O)-, -C3-C8 carbocyclic-OC(=O)-, -O-(C1-C8 alkyl)-OC(=O)-, -arylene-OC(=O)-, -C1-C 10 Alkylene-arylene-OC(=O)-, -arylene-C1-C 10 Alkylene -OC(=O)-, -C1-C 10 Alkylene -(C3-C8 carbide ring)-OC(=O)-, -(C3-C8 carbide ring)-C1-C 10Alkylene -OC(=O)-, -C3-C8 heterocyclic -OC(=O)-, -C1-C 10 Alkylene-(C3-C8 heterocyclic)-OC(=O)- and -(C3-C8 heterocyclic)-C1-C 10 Alkylene-OC(=O)-. In some cases, S 3 It may be optionally substituted by one or more substituents selected from the following: (i) halogen, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -OS(O)2R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 (ii) C and -CN; 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbocyclic rings and 3 to 10-membered heterocycles; and (iii) C 3-10A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group. In some cases, S 3 It may be optionally substituted by one or more substituents selected from the following: (i) halogen, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -OS(O)2R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 ) and -CN. In some cases, S 3 It is unreplaced. In some cases, S 3 It is a replacement. In some cases, S 3 It is a phenylene oxide. In some cases, S 3 for .

[0168] In some embodiments, for formula (III) connectors or salts, or for formulas (X), (XIII), (I), (Ia), (Ib), (II-A), (II-B), (II-E), (II-F), (II-G) drug-conjugates or salts, or formulas (XX), (XXIII), (A), (Aa), (Ab), (A-3), (A-4), (A-5), or (A-6) conjugates or salts, S 4 Selected from (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement. In some cases, S 4 Selected from (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 -, -O-, -C(O)- substitution. In some cases, S 4 Selected from (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 -, -O-, and -C(O)- substitutions. In some cases, S 4 Selected from: (i) optional substitutions of C8-C 12 Alkylene, wherein C8-C 12 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 -, -O-, and -C(O)- substitutions. In some cases, S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement. In some cases, S 4 Selected from: (i) optional substitutions of C6-C 10 Alkylene, wherein C6-C 10 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 -, -O-, or -C(O)- are used as substitutes. In some cases, S 4 It is an optionally substituted C1 alkylene group. In some cases, S 4 It is an optionally substituted C2 alkylene group. In some cases, S 4 It is an optionally substituted C3 alkylene group. In some cases, S 4 It is an optionally substituted C4 alkylene group. In some cases, S 4 It is an optionally substituted C5 alkylene group. In some cases, S 4 It is an optionally substituted C6 alkylene group. In some cases, S 4 It is an optionally substituted C7 alkylene group. In some cases, S 4 It is an optionally substituted C8 alkylene group. In some cases, S 4 It is an optionally substituted C9 alkylene group. In some cases, S 4 C is an optional replacement 10 Alkylene. In some cases, S 4 C is an optional replacement 11 Alkylene. In some cases, S 4 C is an optional replacement 12 Alkylene. In some cases, S 4 C is an optional replacement 13 Alkylene. In some cases, S 4 C is an optional replacement 14 Alkylene. In some cases, S 4 C is an optional replacement 15 Alkylene. In some cases, S 4 C is an optional replacement 16Alkylene. In some cases, S 4 C is an optional replacement 17 Alkylene. In some cases, S 4 C is an optional replacement 18 Alkylene. In some cases, S 4 C is an optional replacement 19 Alkylene. In some cases, S 4 C is an optional replacement 20 Alkylene. In some cases, S 4 One or more alkylene units of the alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、- S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement. In some cases, S 4 One or more alkylene units of the alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 - or -C(O)- substitution. In some cases, S 4 One or more alkylene units of the alkylene group are optionally and independently prefixed with -N(R) 20 - Replacement. In some cases, S 4 One or more alkylene units of the alkylene group are optionally and independently prefixed with -N(R) 20 C(O)-substitution. In some cases, S 4 One or more alkylene units of the alkylene group are optionally and independently surrounded by -C(O)N(R) 20 - Replacement. In some cases, S 4 One or more alkylene units of the alkylene group are optionally and independently replaced by -C(O)-. In some cases, S 4 One or more alkylene units of the alkylene group are optionally and independently replaced by -O-. In some cases, if the alkylene unit of the alkylene group is replaced, the alkylene group may be referred to as the resulting alkylene group. In some cases, if S 4 If two or more alkylene units are replaced, the replaced alkylene units are not adjacent alkylene units. In some cases, if S 4If two or more alkylene units are replaced, the adjacent alkylene units of the resulting alkylene group are not replaced. In some cases, if S 4 If two or more alkylene units are replaced, the resulting alkylene group does not have the heavy complex atoms of the adjacent alkylene units. In some cases, if S 4 If two or more alkylene units are replaced, the resulting alkylene unit will not have repeating identical heteroatoms in adjacent alkylene units. In some cases, if S 4 If two or more alkylene units are replaced, the resulting alkylene unit does not have -NN- or -OO-. In some cases, if S 4 If two or more alkylene units are replaced, the resulting alkylene unit is a stable alkylene. In some cases, if S 4 When two or more alkylene units are replaced, the resulting alkylene unit is an unreacted alkylene. In some cases, the resulting alkylene has only one heteroatom. In some cases, the resulting alkylene has only two heteroatoms, where the two heteroatoms are distinct from each other. In some cases, the resulting alkylene has only two heteroatoms, where the two heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only three heteroatoms, where the three heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only four heteroatoms, where the four heteroatoms are not adjacent to each other. In some cases, the alkylene has zero substituted units. In some cases, the alkylene has one substituted unit. In some cases, the alkylene has two substituted units. In some cases, the alkylene has one substituted unit. In some cases, the alkylene has three substituted units. In some cases, the alkylene has one substituted unit. In some cases, the alkylene has four substituted units. In some cases, the alkylene has one substituted unit. In some cases, the alkylene has five substituted units. In some cases, S 4 The optional substituents on the surface are independently selected each time they appear: (i) halogens, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30)2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 (ii) C and -CN; 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles. In some cases, S 4 The optional substituents on the surface are independently selected each time they appear: (i) halogens, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 ) and -CN. In some cases, S 4 The optional substituents on the [substituent name] are independently selected each time they appear: halogen, -OR 30 -N(R) 30 2. =O and -CN. In some cases, S 4The optional substituents on the surface are independently selected each time they appear: =O. In some cases, S 4 Selected from , and In some cases, S 4 for In some cases, S 4 for In some cases, S 4 for .

[0169] In some implementations, for formula (III) connectors or salts, or for formulas (X), (XI), (XII), (XIII), (I), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (I-AA), (IB), (II-A), (II-B), (II-C), (II-D), or (II-G) drug-connectors or salts, it further includes attaching the targeting unit to M. 1 To form a conjugate, wherein the drug-connector M 1 It reacts with the target unit and forms a covalent bond with it. In some cases, the target unit is selected from the antibody or its antigen-binding portion. In some cases, the average drug-to-target unit ratio of the conjugate is about 1 to 10. In some cases, the target unit is selected from the antibody or its antigen-binding portion. In some cases, the average drug-to-target unit ratio of the conjugate is about 1 to 8. In some cases, the average drug-to-target unit ratio of the conjugate is about 1 to 5. In some cases, the average drug-to-target unit ratio of the conjugate is about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, or about 10. In some cases, the average drug-to-target unit ratio (DAR) of the conjugate is about 8.

[0170] In some implementations, for conjugates or salts of formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), (A-3), or (A-4), M 2 This refers to a connecting unit. In some cases, a connecting unit is a component that links different parts of a conjugate together. In some cases, a connecting unit can connect a targeting unit to S. 3 (If it exists) or to S 2In some cases, the linker unit bonds to the sulfur atom of the target unit. In some cases, the linker unit bonds to the sulfur atom of the target unit via a maleimide group. In some cases, the sulfur atom may be derived from, for example, a thiol group of the target unit (e.g., a thiol group of an interchain disulfide bond). In some cases, M 2 for In some cases, M 2 for In some cases, M 2 for In some cases, M 2 for In some cases, M 2 for In some cases, M 2 for In some cases, M 2 It is -CH2-C(O)NH-. In some cases, M 2 via M 2 The disulfide bond between the sulfur atom in M ​​and the sulfur atom in the target unit is connected to the target unit. In some cases, M 2 for In some cases, the linker unit forms a bond with the primary or secondary amino groups of the target unit. In some cases, M 2 Cystine residues are attached to the target unit via the target unit.

[0171] In one respect, this disclosure provides a type (III) connector: Equation (III) Or its pharmaceutically acceptable salt, wherein; n is selected from 0 and 1; m is selected from 0 and 1; Where at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is -OT 1 and -NH-T 2 ; T 1 For sugar-cuttable units; T 2 It is a peptide cleavable unit; S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20)C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, where C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 3 Selected from the spacer region, wherein the spacer region is preferably phenylene, wherein S 3 To indicate whether something exists or does not exist; S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement; Where M 1 K 1 K 2 S 1 S 2 S 3 and S 4 The optional substituents on the surface are selected independently each time they appear: (iv) Halogens, -OR 30 -N(R) 30 )2、-SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30)2、-NO2、=O、=S、=N(R 30 ) and -CN; (ii) C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles; and (iii) C 3-10 A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group; M 1 These are groups that can react with ligands to form linker units; K 1 Selected from: (iv) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; wherein when X is CH, D is eczema or MMAE, m is 1, n is 0, and K 1 It is polysarcosine, which contains 2-9 sarcosine or 13-30 sarcosine. K 2 Selected from: (iv) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and Each R 30 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and R 50 Substituents selected from those capable of reacting with nucleophilic groups on the pharmaceutical unit.

[0172] In some implementations, for type (III) connectors, R 50 Substituents selected from those capable of reacting with the nucleophilic group on the drug. In some cases, the nucleophilic group on the drug contains nitrogen. In some cases, the nucleophilic group on the drug contains oxygen.

[0173] In some implementations, for type (III) connectors, R 50 Selected from In some cases, R 50 Selected from -OH. In some cases, R 50 Selected from In some cases, R 50 Selected from .

[0174] In some implementations, the formula (X) drug-connector is selected from: ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;and .

[0175] In some implementations, the formula (X) drug-connector is selected from:

[0176]

[0177] , , , , , 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , , , , , , , , , , , , , , , , ,

[0178] and .

[0179] In some implementations, the conjugate of formula (XX) or formula (A) is represented as:

[0180]

[0181] , , , , , , 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , , , , , , , , , , , , , , ; ;

[0182] and ; Each L represents a target unit; and each DAR is a drug-to-antibody ratio. In some cases, the DAR is determined using RP-HPLC. In some cases, the DAR is determined using RP-HPLC as in Example 31. In some cases, the DAR is up to about 16. In some cases, the DAR is about 8. In some cases, the DAR is up to about 10. In some cases, the DAR is at least about 1. In some cases, the DAR is at least about 2. In some cases, the DAR is at least about 4. In some cases, the DAR is at least about 8. In some cases, the DAR is up to about 8. In some cases, the DAR is about 1 to about 16. In some cases, the DAR is about 4 to about 12. In some cases, the DAR is about 6 to about 10. In some cases, the DAR is about 7 to about 9. In some cases, the DAR is about 8 to about 10. In some cases, the DAR is about 6 to about 8. In some cases, L is a UC-961 antibody. In some cases, L is a ROR2 antibody. In some cases, L is an antibody or its antigen-binding moiety. In some cases, L is an antibody. In some cases, L is a peptide. In some cases, L comprises one or more amino acids.

[0183] In some implementations, the conjugate of formula (A) is represented as: ; ; ; ; ; ;or Each L represents a target unit; and each DAR represents the drug-to-antibody ratio. In some cases, conjugates of formula (A) are represented as: , where each L is a targeting unit; and each DAR is the drug-to-antibody ratio. In some cases, the conjugate of formula (A) is represented as: , Each L represents a target unit; and each DAR is a drug-to-antibody ratio. In some cases, the DAR is determined using RP-HPLC. In some cases, the DAR is determined using RP-HPLC as in Example 31. In some cases, the DAR is up to about 16. In some cases, the DAR is about 8. In some cases, the DAR is up to about 10. In some cases, the DAR is at least about 1. In some cases, the DAR is at least about 2. In some cases, the DAR is at least about 4. In some cases, the DAR is at least about 8. In some cases, the DAR is up to about 8. In some cases, the DAR is about 1 to about 16. In some cases, the DAR is about 4 to about 12. In some cases, the DAR is about 6 to about 10. In some cases, the DAR is about 7 to about 9. In some cases, the DAR is about 8 to about 10. In some cases, the DAR is about 6 to about 8. In some cases, the targeting unit comprises an antibody containing a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:1 and the light chain variable region is SEQ ID NO:2. In some cases, the targeting unit comprises an antibody containing a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:3 and the light chain variable region is SEQ ID NO:4. In some cases, L is a UC-961 antibody. In some cases, L is a ROR2 antibody.

[0184] In some implementations, the conjugate of formula (A) is represented as: ; ; ; ; ; ; ; ; ; ; ; ; or Each L represents a target unit; and each DAR represents the drug-to-antibody ratio. In some cases, conjugates of formula (A) are represented as: , where each L is a targeting unit; and each DAR is the drug-to-antibody ratio. In some cases, the conjugate of formula (A) is represented as: , where each L is a targeting unit; and each DAR is the drug-to-antibody ratio. In some cases, the conjugate of formula (A) is represented as: , where each L is a targeting unit; and each DAR is the drug-to-antibody ratio. In some cases, the conjugate of formula (A) is represented as: , where each L is a targeting unit; and each DAR is the drug-to-antibody ratio. In some cases, the conjugate of formula (A) is represented as: , where each L is a targeting unit; and each DAR is the drug-to-antibody ratio. In some cases, the conjugate of formula (A) is represented as: , where each L is a targeting unit; and each DAR is the drug-to-antibody ratio. In some cases, the conjugate of formula (A) is represented as: , where each L is a targeting unit; and each DAR is the drug-to-antibody ratio. In some cases, the conjugate of formula (A) is represented as: Each L is a targeting unit; and each DAR is a drug-to-antibody ratio. In some cases, the DAR is determined using RP-HPLC. In some cases, the DAR is determined using RP-HPLC as in Example 37. In some cases, the DAR is up to about 16. In some cases, the DAR is about 8. In some cases, the DAR is up to about 10. In some cases, the DAR is at least about 1. In some cases, the DAR is at least about 2. In some cases, the DAR is at least about 4. In some cases, the DAR is at least about 8. In some cases, the DAR is up to about 8. In some cases, the DAR is about 1 to about 16. In some cases, the DAR is about 4 to about 12. In some cases, the DAR is about 6 to about 10. In some cases, the DAR is about 7 to about 9. In some cases, the DAR is about 8 to about 10. In some cases, the DAR is about 6 to about 8. In some cases, the targeting unit comprises an antibody containing a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:1 and the light chain variable region is SEQ ID NO:2. In some cases, the targeting unit comprises an antibody containing a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:3 and the light chain variable region is SEQ ID NO:4. In some cases, L is a UC-961 antibody. In some cases, L is a ROR2 antibody.

[0185] In some implementations, the (Aa) conjugate or salt is represented as: In some cases, DAR is determined using RP-HPLC. In some cases, DAR is determined using RP-HPLC as in Example 31. In some cases, DAR is up to about 16. In some cases, DAR is about 8. In some cases, DAR is up to about 10. In some cases, DAR is at least about 1. In some cases, DAR is at least about 2. In some cases, DAR is at least about 4. In some cases, DAR is at least about 8. In some cases, DAR is up to about 8. In some cases, DAR is about 1 to about 16. In some cases, DAR is about 4 to about 12. In some cases, DAR is about 6 to about 10. In some cases, DAR is about 7 to about 9. In some cases, DAR is about 8 to about 10. In some cases, DAR is about 6 to about 8. In some cases, DAR is the ratio of drug (D) to antibody (L). In some cases, the drug in DAR is ixotecan. In some cases, the drug in DAR is ixotecan. In some cases, the targeting unit has an antibody comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:1 and the light chain variable region is SEQ ID NO:2. In some cases, the targeting unit has an antibody comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:3 and the light chain variable region is SEQ ID NO:4. In some cases, L is UC-961. In some cases, L is a ROR2 antibody. In some cases, L is a UC-961 antibody.

[0186] In some implementations, the (Ab) conjugate or salt is represented as: Where L is the target unit; and DAR is the drug-to-antibody ratio. In some cases, DAR is determined using RP-HPLC. In some cases, DAR is determined using RP-HPLC as in Example 37. In some cases, DAR is up to about 16. In some cases, DAR is about 8. In some cases, DAR is up to about 10. In some cases, DAR is at least about 1. In some cases, DAR is at least about 2. In some cases, DAR is at least about 4. In some cases, DAR is at least about 8. In some cases, DAR is up to about 8. In some cases, DAR is about 1 to about 16. In some cases, DAR is about 4 to about 12. In some cases, DAR is about 6 to about 10. In some cases, DAR is about 7 to about 9. In some cases, DAR is about 8 to about 10. In some cases, DAR is about 6 to about 8. In some cases, DAR is the drug (D) to antibody (L) ratio. In some cases, the drug in the DAR is eczema. In some cases, the drug for DAR is eczema. In some cases, the targeting unit has an antibody comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:1 and the light chain variable region is SEQ ID NO:2. In some cases, the targeting unit has an antibody comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:3 and the light chain variable region is SEQ ID NO:4. In some cases, L is UC-961. In some cases, L is a ROR2 antibody. In some cases, L is UC-961.

[0187] In some implementations, the (Aa) conjugate or salt is represented as: In some cases, DAR is determined using RP-HPLC. In some cases, DAR is determined using RP-HPLC as in Example 37. In some cases, DAR is up to about 16. In some cases, DAR is about 8. In some cases, DAR is up to about 10. In some cases, DAR is at least about 1. In some cases, DAR is at least about 2. In some cases, DAR is at least about 4. In some cases, DAR is at least about 8. In some cases, DAR is up to about 8. In some cases, DAR is about 1 to about 16. In some cases, DAR is about 4 to about 12. In some cases, DAR is about 6 to about 10. In some cases, DAR is about 7 to about 9. In some cases, DAR is about 8 to about 10. In some cases, DAR is about 6 to about 8. In some cases, DAR is the ratio of drug (D) to antibody (L). In some cases, the drug in DAR is ixotecan. In some cases, the drug in DAR is ixotecan. In some cases, the targeting unit has an antibody comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:1 and the light chain variable region is SEQ ID NO:2. In some cases, the targeting unit has an antibody comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:3 and the light chain variable region is SEQ ID NO:4. In some cases, L is UC-961. In some cases, L is a ROR2 antibody. In some cases, the antibody is UC-961.

[0188] In some implementations, the (Ab) conjugate or salt is represented as: Where L is the target unit; and DAR is the drug-to-antibody ratio. In some cases, DAR is determined using RP-HPLC. In some cases, DAR is determined using RP-HPLC as in Example 37. In some cases, DAR is up to about 16. In some cases, DAR is about 8. In some cases, DAR is up to about 10. In some cases, DAR is at least about 1. In some cases, DAR is at least about 2. In some cases, DAR is at least about 4. In some cases, DAR is at least about 8. In some cases, DAR is up to about 8. In some cases, DAR is about 1 to about 16. In some cases, DAR is about 4 to about 12. In some cases, DAR is about 6 to about 10. In some cases, DAR is about 7 to about 9. In some cases, DAR is about 8 to about 10. In some cases, DAR is about 6 to about 8. In some cases, DAR is the drug (D) to antibody (L) ratio. In some cases, the drug in the DAR is eczema. In some cases, the targeting unit has an antibody comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:1 and the light chain variable region is SEQ ID NO:2. In some cases, the targeting unit has an antibody comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:3 and the light chain variable region is SEQ ID NO:4. In some cases, L is UC-961. In some cases, L is a ROR2 antibody. In some cases, the drug for DAR is eczema. In some cases, the antibody is UC-961.

[0189] In some implementations, the (Ab) conjugate or salt is represented as: In some cases, DAR is determined using RP-HPLC. In some cases, DAR is determined using RP-HPLC as in Example 37. In some cases, DAR is up to about 16. In some cases, DAR is about 8. In some cases, DAR is up to about 10. In some cases, DAR is at least about 1. In some cases, DAR is at least about 2. In some cases, DAR is at least about 4. In some cases, DAR is at least about 8. In some cases, DAR is up to about 8. In some cases, DAR is about 1 to about 16. In some cases, DAR is about 4 to about 12. In some cases, DAR is about 6 to about 10. In some cases, DAR is about 7 to about 9. In some cases, DAR is about 8 to about 10. In some cases, DAR is about 6 to about 8. In some cases, DAR is the ratio of drug (D) to antibody (L). In some cases, the drug in DAR is ixotecan. In some cases, the drug in DAR is ixotecan. In some cases, the targeting unit has an antibody comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:1 and the light chain variable region is SEQ ID NO:2. In some cases, the targeting unit has an antibody comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:3 and the light chain variable region is SEQ ID NO:4. In some cases, L is UC-961. In some cases, L is a ROR2 antibody. In some cases, the antibody is UC-961.

[0190] In some implementations, the (Ab) conjugate or salt is represented as: Where L is the target unit; and DAR is the drug-to-antibody ratio. In some cases, DAR is determined using RP-HPLC. In some cases, DAR is determined using RP-HPLC as in Example 37. In some cases, DAR is up to about 16. In some cases, DAR is about 8. In some cases, DAR is up to about 10. In some cases, DAR is at least about 1. In some cases, DAR is at least about 2. In some cases, DAR is at least about 4. In some cases, DAR is at least about 8. In some cases, DAR is up to about 8. In some cases, DAR is about 1 to about 16. In some cases, DAR is about 4 to about 12. In some cases, DAR is about 6 to about 10. In some cases, DAR is about 7 to about 9. In some cases, DAR is about 8 to about 10. In some cases, DAR is about 6 to about 8. In some cases, DAR is the drug (D) to antibody (L) ratio. In some cases, the drug in the DAR is eczema. In some cases, the drug for DAR is eczema. In some cases, the targeting unit has an antibody comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:1 and the light chain variable region is SEQ ID NO:2. In some cases, the targeting unit has an antibody comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:3 and the light chain variable region is SEQ ID NO:4. In some cases, L is UC-961. In some cases, L is a ROR2 antibody. In some cases, the antibody is UC-961.

[0191] In some embodiments, the conjugate or salt of formula (XX), formula (XXIII), or formula (A) is represented as follows: Where L is the target unit; and DAR is the drug-to-antibody ratio. In some cases, conjugates are represented as: Where L is the target unit; and DAR is the drug-to-antibody ratio. In some cases, conjugates are represented as: Where L is the target unit; and DAR is the drug-to-antibody ratio. In some cases, conjugates are represented as: Where L is the target unit; and DAR is the drug-to-antibody ratio. In some cases, conjugates are represented as: Where L is the target unit; and DAR is the drug-to-antibody ratio. In some cases, conjugates are represented as: Where L is the target unit; and DAR is the drug-to-antibody ratio. In some cases, conjugates are represented as: Where L is the target unit; and DAR is the drug-to-antibody ratio. In some cases, conjugates are represented as: Where L is the target unit; and DAR is the drug-to-antibody ratio. In some cases, conjugates are represented as: Where L is the target unit; and DAR is the drug-to-antibody ratio. In some cases, conjugates are represented as: Where L is the target unit; and DAR is the drug-to-antibody ratio. In some cases, DAR is determined using RP-HPLC. In some cases, DAR is determined using RP-HPLC as in Example 37. In some cases, DAR is up to about 16. In some cases, DAR is about 8. In some cases, DAR is up to about 10. In some cases, DAR is at least about 1. In some cases, DAR is at least about 2. In some cases, DAR is at least about 4. In some cases, DAR is at least about 8. In some cases, DAR is up to about 8. In some cases, DAR is about 1 to about 16. In some cases, DAR is about 4 to about 12. In some cases, DAR is about 6 to about 10. In some cases, DAR is about 7 to about 9. In some cases, DAR is about 8 to about 10. In some cases, DAR is about 6 to about 8. In some cases, DAR is the drug (D) to antibody (L) ratio. In some cases, the drug in the DAR is eczema. In some cases, the drug for DAR is eczema. In some cases, the targeting unit has an antibody comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:1 and the light chain variable region is SEQ ID NO:2. In some cases, the targeting unit has an antibody comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:3 and the light chain variable region is SEQ ID NO:4. In some cases, L is UC-961. In some cases, L is a ROR2 antibody. In some cases, L is a UC-961 antibody.

[0192] Table A: Specific Conjugates of this Disclosure

[0193] The conjugates in Table A have a DAR of about 1 to about 8. Some conjugates have a DAR of about 2 to about 8. Some conjugates have a DAR of about 2. Some conjugates have a DAR of about 8.

[0194] Included in this disclosure are salts, particularly pharmaceutically acceptable salts of the compounds described herein. Compounds of the invention having sufficient acidity, sufficient basicity, or both functional groups can react with a variety of inorganic bases and any of inorganic and organic acids to form salts. Alternatively, inherently charged compounds (such as those having a quaternary nitrogen) can form salts with suitable counterions (e.g., halides such as bromide, chloride, or fluoride ions, particularly bromide ions).

[0195] Chemical entities with carbon-carbon double bonds or carbon-nitrogen double bonds can be... Z- or E- Form (or Cis or trans ( ) exists. Furthermore, some chemical entities can exist in various tautomer forms. Unless otherwise stated, the compounds described herein are intended to include all Z- , E- and tautomer forms.

[0196] A "tautomer" is a molecule in which a proton may transfer from one atom of the molecule to another atom of the same molecule. In some embodiments, the compounds described herein exist as tautomers. Where tautomerism is possible, a chemical equilibrium will exist between the tautomers. The exact proportions of the tautomers depend on several factors, including physical state, temperature, solvent, and pH. Some examples of tautomeric equilibria include: .

[0197] In some embodiments, the compounds disclosed herein are used in different enriched isotopic forms, for example, in 2 H, 3 H, 11 C 13 C and / or 14 Content enrichment of C. In one particular embodiment, the compound is deuterated at at least one position. Such deuterated forms can be prepared by the procedures described in U.S. Patent Nos. 5,846,514 and 6,334,997. As described in U.S. Patent Nos. 5,846,514 and 6,334,997, deuteration can improve metabolic stability and / or efficacy, thereby prolonging the duration of drug action.

[0198] Unless otherwise stated, the compounds described herein are intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having this structure but with hydrogen substituted for deuterium or tritium, or with carbon enriched... 13 C or 14 All compounds in which C is substituted with carbon are within the scope of this disclosure.

[0199] The compounds disclosed herein optionally contain atomic isotopes in non-natural proportions at one or more atoms constituting such compounds. For example, the compounds may use isotopes such as deuterium (… 2 H), tritium ( 3 H), Iodine-125 ( 125 I) or carbon-14 ( 14 C) Marking. Also consider using... 2 H, 11 C 13 C 14 C 15 C 12 N、 13 N、15 N、 16 N、 16 O、 17 O、 14 F, 15 F, 16 F, 17 F, 18 F, 33 S, 34 S, 35 S, 36 S, 35 Cl、 37 Cl、 79 Br、 81 Br and 125 I. Isotope substitution. All isotopic variants of the compounds of this invention, whether or not radioactive, are covered within the scope of this invention.

[0200] In some embodiments, some or all of the compounds disclosed herein 1 H atoms are 2 H atom substitution. Methods for synthesizing deuterium-containing compounds are known in the art, and include, but are not limited to, the following synthetic methods.

[0201] Deuterium-substituted compounds were synthesized using various methods described in the following literature: Dean, Dennis C.; Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [In: Curr., Pharm. Des., 2000; 6(10)] 2000, 110 pp; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony. Synthesis of Radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0202] Deuterated starting materials are readily available and can be used to synthesize deuterium-containing compounds using the synthetic methods described herein. A wide range of deuterium-containing reagents and building blocks are available from chemical suppliers such as Aldrich Chemical Co.

[0203] The compounds of the present invention also include crystalline and amorphous forms of these compounds, pharmaceutically acceptable salts, and active metabolites of these compounds having the same type of activity, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, nonsolventized polymorphs (including anhydrous compounds), conformational polymorphs and amorphous forms of the compounds, and mixtures thereof.

[0204] The compounds described herein may exist in some cases as diastereomers, enantiomers, or other stereoisomers. Unless an absolute stereochemistry is specified, the compounds described herein include all diastereomers, enantiomers, and epimers, as well as suitable mixtures thereof. Separation of stereoisomers can be performed by chromatography or by forming diastereomers and then recrystallizing or chromatography, or any combination thereof. (Jean Jacques, Andre Collet, Samuel H. Wilen, “Enantiomers, Racemates and Resolutions”, John Wiley and Sons, Inc., 1981, for which this disclosure is incorporated herein by reference). Stereoisomers can also be obtained by stereoselective synthesis.

[0205] The methods and compositions described herein include the use of amorphous and crystalline forms (also known as polymorphs). The compounds described herein may be in the form of pharmaceutically acceptable salts. Furthermore, in some embodiments, active metabolites of these compounds having the same type of activity are included within the scope of this disclosure. Additionally, the compounds described herein may be present in a non-solventized form or in a solvated form with pharmaceutically acceptable solvents such as water, ethanol, etc. The solvated form of the compounds described herein is also considered part of this disclosure.

[0206] In some embodiments, the compound or salt of a compound may be a prodrug, for example, wherein the hydroxyl group in the parent compound is present in the form of an ester or carbonate or carboxylic acid. The term "prodrug" is intended to cover compounds that are converted to pharmaceutical agents of this disclosure under physiological conditions. One method for preparing a prodrug includes hydrolysis under physiological conditions to reveal one or more selected moieties of the desired molecule. In other embodiments, the prodrug is converted by the enzymatic activity of a host animal, such as specific target cells within the host animal. For example, esters or carbonates (e.g., esters or carbonates of alcohols or carboxylic acids and esters of phosphonates) are preferred prodrugs of this disclosure.

[0207] The prodrug forms of the compounds described herein, wherein the prodrugs are metabolized in vivo to prepare compounds as shown herein, are included within the scope of the claims. In some cases, some of the compounds described herein may be prodrugs of another derivative or active compound.

[0208] Prodrugs are often useful because, in some cases, they can be more readily administered than the parent drug. For example, they may be bioavailable through oral administration, whereas the parent drug may not. Prodrugs can help enhance the cellular permeability of a compound relative to the parent drug. Prodrugs may also have higher solubility in pharmaceutical compositions than the parent drug. Prodrugs can be engineered as reversible drug derivatives to act as modifiers to enhance drug transport to site-specific tissues or increase drug retention within cells.

[0209] In some embodiments, the prodrug design increases the lipophilicity of the agent. In some embodiments, the prodrug design increases effective water solubility. See, for example, Fedorak. et al. , Am. J. Physiol. , 269:G210-218(1995); McLoed et al. , Gastroenterol , 106:405-413 (1994); Hochhaus et al. , Biomed. Chrom., 6:283-286 (1992); J. Larsen and H. Bundgaard, Int. J. Pharmaceutics, 37,87 (1987); J. Larsen et al. , Int. J. Pharmaceutics , 47, 103 (1988); Sinkula et al. , J. Pharm. Sci ., 64:181-210 (1975); T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of the ACS Symposium Series; and Edward B. Roche, Bioreversible Carriers in Drug Design According to the American Pharmaceutical Association and Pergamon Press, 1987, all references are incorporated herein by reference for the purposes of this disclosure. According to another embodiment, this disclosure provides a method for producing compounds as defined above. The compounds can be synthesized using conventional techniques. Advantageously, these compounds are readily synthesized from readily available starting materials.

[0210] Synthetic chemical transformations and methods that can be used to synthesize the compounds described herein are known in the art, including, for example, those described by R. Larock. Comprehensive Organic Transformations (1989); TW Greene and PGM Wuts, Protective Groups in Organic Synthesis, 2d. Ed. (1991); L. Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis (1994); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis Those described in (1995).

[0211] Targeting unit In some embodiments, for drug-connectors or salts of formulas (I), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (I-AA), (I-AB), (IB), (II-A), and (II-B) (each of which further comprises a targeting unit), or for conjugates or salts of formulas (A), (Aa), (Ab), (A-1), (A-2), (A-3), or (A-4), the targeting unit is selected from antibodies or antigen-binding fragments thereof. In some cases, the targeting unit is selected from chimeric antibodies, humanized antibodies, and human antibodies. In some cases, the targeting unit performs a targeting function. In some cases, the targeting unit specifically binds to a target molecule. In some cases, specific binding means that the targeting unit described herein (e.g., an antibody or a portion thereof) binds to a molecule having a KD 10 -5 M (10000 nM) or lower, such as 10 -6 M, 10 -7 M, 10 -8 M, 10 -9 M, 10 -10 M, 10 -11 M, 10 -12 The ability to bind to targets of M or lower. In some cases, when a targeting unit preferentially recognizes its target in a complex mixture of proteins and / or macromolecules, it is said to specifically bind to its target.

[0212] In some implementations, for drug-connectors or salts of formulas (I), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-A), and (II-B), or for conjugates or salts of formulas (A), (Aa), (Ab), (A-1), (A-2), (A-3), or (A-4), the targeting unit is an antibody or its antigen-binding moiety is a bispecific or multispecific binder. Bispecific and multispecific antibodies include the following: scFv1-ScFv2, scFv1 2-Fc-ScFv2 2, IgG-scFv, DVD-Ig, triomab / quadroma, dual-function IgG, scFv2-Fc, TandAb, and scFv-HSA-scFv. In some implementations, IgG-scFv is IgG(H)-scFv, scFv-(H)IgG, IgG(L)-scFv, svFc-(L)IgG, 2scFV-IgG, or IgG-2scFV.

[0213] In some implementations, for drug-connectors or salts of formula (I), formula (IA), formula (Ia), formula (I-AAa), formula (Ib), formula (I-AAb), formula (IB), formula (II-A), formula (II-B), or for conjugates or salts of formula (A), formula (Aa), formula (Ab), formula (A-1), formula (A-2), formula (A-3), or formula (A-4), the targeting unit is able to bind to the extracellular domain of ROR1.

[0214] In some implementations, the targeting unit is UC-961 for drug-connectors or salts of formulas (I), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-A), and (II-B), or for conjugates or salts of formulas (A), (Aa), (Ab), (A-1), (A-2), (A-3), or (A-4). In some cases, L is UC-961.

[0215] In some implementations, for drug-connectors or salts of formulas (I), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-A), and (II-B), or for conjugates or salts of formulas (A), (Aa), (Ab), (A-1), (A-2), (A-3), or (A-4), the targeting unit is a cancer-associated antigen such as CD19, CD20, CD30, CD33, CD38, CA125, MUC-1, prostate-specific membrane antigen (PSMA), CD44 surface adhesion molecule, mesothelin (MLSN), carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR), EGFRvIII, vascular endothelial growth factor receptor-2 (VEGFR2), high molecular weight melanoma-associated antigen (HMW-MAA), MAGE-A1, IL-13R-a2, GD2, 1p19q, ABL1, or AKT1. ALK, APC, AR, ATM, BRAF, BRCA1, BRCA2, cKIT, cMET, CSF1R, CTNNB1, FGFR1, FGFR2, FLT3, GNA11, GNAQ, G NAS, HRAS, IDH1, IDH2, JAK2, KDR (VEGFR2), KRAS, MGMT, MGMT-Me, MLH1, MPL, NOTCH1, NRAS, PDGFRA, Pg p, PIK3CA, PR, PTEN, RET, RRM1, SMO, SPARC, TLE3, TOP2A, TOPO1, TP53, TS, TUBB3, VHL, CDH1, ERBB4, FB XW7, HNF1A, JAK3, NPM1, PTPN11, RB1, SMAD4, SMARCB1, STK1, MLH1, MSH2, MSH6, PMS2, ROS1, ERCC1, 5T4 (TPBG), B7-H3, CCR7, CD105, CD22, CD46, CD47, CD56, CD70, CD71, CD79b, CDH6, CLDN6, CLDN18.2, CLEC12A, DLL3, DR5, ERBB3 (HER3), EPCAM, FORR1, IGF1R, IL2RA (CD25), IL3RA, ITGB6, LIV-1, LRRC15, mesothelin (MSLN), NaPi2b (SLC34A2), conjugated 4, PTK7, ROR1, SEZ6, SLC44A4, SLITRK6, tissue factor (TF), TROP2 or B7-H4.

[0216] In some implementations, the targeting unit specifically binds to targets such as CD19, CD20, CD30, CD33, CD70, LIV-1, or EGFRv3.

[0217] In some embodiments, for drug-connectors or salts of formulas (I), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (I-AA), (I-AB), (IB), (II-A), and (II-B) (each of which further comprises a targeting unit), or for conjugates or salts of formulas (A), (Aa), (Ab), (A-1), (A-2), (A-3), or (A-4), the targeting unit comprises at least one amino acid. In some cases, the targeting unit is one or more amino acids. In some cases, the targeting unit comprises one or more natural amino acids. In some cases, the targeting unit comprises one or more non-natural amino acids. In some cases, non-natural amino acids (p-acetylphenylalanine or pAcF and p-azidomethyl-L-phenylalanine or pAMF) or short peptide tags. In some cases, the targeting unit comprises cysteine. In some cases, the targeting unit comprises glutamine. In some cases, the targeting unit is a peptide having fewer than 50 amino acids. In some cases, the targeting unit is a peptide with fewer than 40 amino acids. In some cases, the targeting unit is a peptide with fewer than 30 amino acids. In some cases, the targeting unit is a peptide with fewer than 20 amino acids. In some cases, the targeting unit is a peptide with more than 50 amino acids. In some cases, the targeting unit is a peptide with more than 40 amino acids. In some cases, the targeting unit is a peptide with more than 30 amino acids. In some cases, the targeting unit is a peptide with more than 20 amino acids. In some cases, the targeting unit is a peptide with more than 10 amino acids. In some cases, the targeting unit is a peptide with more than 5 amino acids. In some cases, the targeting unit is a peptide with about 1 to about 50 amino acids. In some cases, the targeting unit is a peptide with about 2 to about 30 amino acids. In some cases, the targeting unit is a peptide with about 3 to about 15 amino acids. In some cases, the targeting unit includes a cyclic peptide.

[0218] In some embodiments, for drug-connectors or salts of formulas (I), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (I-AA), (I-AB), (IB), (II-A), and (II-B) (each of which further comprises a targeting unit), or for conjugates or salts of formulas (A), (Aa), (Ab), (A-1), (A-2), (A-3), or (A-4), the targeting unit has at least one sulfur atom. In some cases, the targeting unit has at least one sulfur atom from a cysteine ​​residue. In some cases, the targeting unit has at least one sulfur atom from a reduced cysteine ​​residue.

[0219] In some embodiments, for drug-connectors or salts of formulas (I), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (I-AA), (I-AB), (IB), (II-A), and (II-B) (each of which further comprises a targeting unit), or for conjugates or salts of formulas (A), (Aa), (Ab), (A-1), (A-2), (A-3), or (A-4), the targeting unit has an antibody comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:1 and the light chain variable region is SEQ ID NO:2. In some cases, the targeting unit has an antibody comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable region is SEQ ID NO:3 and the light chain variable region is SEQ ID NO:4. In some cases, the heavy chain variable region further comprises a heavy chain constant region. In some cases, the heavy chain constant region is an IgG isotype. In some cases, the heavy chain constant region is an IgG1 constant region. In some cases, the heavy chain constant region is an IgG4 constant region.

[0220] In some embodiments, for drug-connectors or salts of formulas (I), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (I-AA), (I-AB), (IB), (II-A), and (II-B) (each of which further comprises a targeting unit), or for conjugates or salts of formulas (A), (Aa), (Ab), (A-1), (A-2), (A-3), or (A-4), the targeting unit, such as an antibody or its antigen-binding portion, or other targeting units, has an antibody constant region. In some cases, the constant region is a fully human constant region. In some cases, the constant region is a humanized constant region. In some cases, the constant region is a non-human constant region. In some cases, the immunoglobulin constant region refers to a heavy chain or light chain constant region. The constant region can be any suitable type, and it can be selected from immunoglobulins, IgA, IgD, IgE, IgG, and IgM classes. Several immunoglobulin classes can be further divided into isotypes, such as IgG1, IgG2, IgG3, IgG4, or IgA1 and IgA2. The heavy chain constant region (Fc) corresponding to different classes of immunoglobulins can be α, δ, ε, γ, and μ, respectively. The light chain can be either kappa (κ) or lambda (λ).

[0221] In some embodiments, the constant region may have an IgG isotype. In some embodiments, the constant region may have an IgG1 isotype. In some embodiments, the constant region may have an IgG2 isotype. In some embodiments, the constant region may have an IgG3 isotype. In some embodiments, the constant region may have an IgG4 isotype. In some embodiments, the constant region may have a hybrid isotype, which includes constant regions derived from two or more isotypes. In some embodiments, the immunoglobulin constant region may be an IgG1 or IgG4 constant region.

[0222] pharmaceutical preparations In some embodiments, this document provides pharmaceutical compositions comprising therapeutically effective amounts of formula (X), formula (XI), formula (XII), formula (XIII), formula (I), formula (IA), formula (Ia), formula (I-AAa), formula (Ib), formula (I-AAb), formula (I-AA), formula (I-AB), formula (IB), formula (II-A), formula (II-B) drug-connector or salt, or for formula (XX), formula (XXI), formula (XXII), formula (XXIII), formula (A), formula (Aa), formula (Ab), formula (A-1), formula (A-2), formula (A-3) or formula (A-4) conjugate or salt (also referred to herein as "pharmaceutical").

[0223] Pharmaceutical compositions can be formulated using one or more physiologically acceptable carriers (including excipients and adjuvants) that facilitate the processing of the pharmaceutical agent into a pharmaceutical formulation. The appropriate formulation depends on the chosen route of administration. An overview of pharmaceutical compositions can be found, for example, in Remington: The Science and Practice of Pharmacy, 19th edition (Easton, Pa., Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, HA and Lachman, L., eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, NY, 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, 7th edition (Lippincott Williams & Wilkins, 1999).

[0224] The compositions and methods disclosed herein can be used to treat individuals in need. In some embodiments, the individual is a mammal such as a human or a non-human mammal. When administered to an animal (such as a human), the composition or agent is preferably administered in the form of a pharmaceutical composition comprising, for example, a pharmaceutical agent and a pharmaceutically acceptable carrier or excipient. Pharmaceutically acceptable carriers are well known in the art and include, for example, aqueous solutions (such as water or physiologically buffered saline) or other solvents or media (such as ethylene glycol, glycerin, oils (such as olive oil), or injectable organic esters). In a preferred embodiment, when such pharmaceutical compositions are used for human administration, particularly for invasive routes of administration (such as injection or implantation routes that circumvent transport or diffusion through the epithelial barrier), the aqueous solution is pyrogen-free or substantially pyrogen-free. For example, the excipient may be selected to achieve delayed release of the agent or selective targeting of one or more cells, tissues, or organs. The pharmaceutical composition may be in the form of dosage units, such as tablets, capsules, granules, reconfigurable lyophilized formulations, powders, solutions, syrups, suppositories, injections, etc. The composition may also be present in transdermal administration systems, such as skin patches. The composition may also be present in solutions suitable for topical application, such as eye drops.

[0225] Pharmaceutically acceptable excipients may contain physiologically acceptable agents, such as those used to stabilize, increase solubility, or enhance the absorption of compounds (e.g., pharmaceutical preparations). Such physiologically acceptable agents include, for example, carbohydrates (such as glucose, sucrose, or dextran), antioxidants (such as ascorbic acid or glutathione), chelating agents, low molecular weight proteins, or other stabilizers or excipients. The choice of pharmaceutically acceptable excipients (including physiologically acceptable agents) depends, for example, on the route of administration of the composition. The formulation or pharmaceutical composition may be a self-emulsifying drug delivery system or a self-microemulsifying drug delivery system. The pharmaceutical composition (formulation) may also be a liposome or other polymer matrix, which may contain compounds such as those of the present invention incorporated therein. For example, liposomes containing phospholipids or other lipids are non-toxic, physiologically acceptable, and metabolizable carriers, and their preparation and administration are relatively simple.

[0226] The pharmaceutical composition (formulation) can be administered to any of the following subjects via a variety of routes of administration, including, for example, oral administration, such as by drenches: aqueous or non-aqueous solutions or suspensions, tablets, capsules (including spray capsules and gelatin capsules), granules, powders, pellets, or pastes for application to the tongue; absorption through the oral mucosa, such as sublingual absorption; absorption through the anus, rectum, or vagina, such as in the form of vaginal suppositories, creams, or foams; parenteral administration, including intramuscular, intravenous, subcutaneous, or intrathecal administration, such as in the form of sterile solutions or suspensions; nasal administration; intraperitoneal administration; subcutaneous administration; transdermal administration, such as in the form of patches for application to the skin; and topical administration, such as in the form of creams, ointments, or sprays for application to the skin, or in the form of eye drops. The compound can also be formulated for inhalation. In some embodiments, the compound can simply be dissolved or suspended in sterile water.

[0227] Pharmaceutical compositions may be sterile aqueous or non-aqueous solutions, suspensions, or emulsions, such as microemulsions. The excipients described herein are merely examples and do not constitute any limitation. An effective amount, or therapeutically effective amount, refers to the amount of one or more pharmaceutical agents administered to a subject in a single dose or a portion of a series of doses that is effective in producing the desired therapeutic effect.

[0228] In general, assays and methods suitable for the treated condition can be used to monitor the treatment effect on the subject. These assays are familiar to those skilled in the art and are described herein. The pharmacokinetics of a drug or one or more metabolites administered to a subject can be monitored by determining the levels of the drug or metabolites in the subject's biological fluids (e.g., blood, blood fractions (e.g., serum), and / or urine, and / or other biological samples or tissues from the subject). Any method practiced in the art and described herein for detecting agents can be used to measure the levels of the drug or metabolites during treatment.

[0229] The dosage of the pharmaceutical agents described herein for the treatment of a disease or condition may depend on the subject's condition, i.e., the stage of the disease, the severity of the symptoms caused by the disease, overall health status, and age, sex, and weight, as well as other factors obvious to a person skilled in the medical field. The pharmaceutical composition may be administered in a manner appropriate for the disease to be treated, as determined by a person skilled in the medical field. In addition to the factors described herein and above related to the use of the pharmaceutical agents for the treatment of a disease or condition, the appropriate duration and frequency of administration of the pharmaceutical agents may be determined or adjusted based on factors such as the patient's condition, the type and severity of the patient's disease, the specific form of the active ingredient, and the method of administration. The optimal dosage of the agent may generally be determined using experimental models and / or clinical trials. The optimal dosage may depend on the subject's body mass, weight, or blood volume. Generally, the minimum dose sufficient to provide effective treatment is preferred. The design and execution of preclinical and clinical studies of the pharmaceutical agents described herein (including those used for prophylactic benefit administration) are entirely within the skill of a person skilled in the relevant field. When two or more pharmaceutical agents are administered to treat a disease or condition, the optimal dosage of each agent may differ, such as being lower than the dosage when either agent is administered alone as a monotherapy. In certain specific embodiments, the two agents may act synergistically or additively, and the dosage of either agent may be lower than that of either agent when administered alone. The daily dosage may be, for example, from about 0.01 mg / kg to 100 mg / kg, such as about 0.1 to 1 mg / kg, about 1 to 10 mg / kg, about 10-50 mg / kg, or about 50-100 mg / kg body weight. In other embodiments, the daily dosage may be from about 0.01 mg / kg to 1000 mg / kg body weight, about 100-500 mg / kg body weight, or about 500-1000 mg / kg body weight. The optimal daily or per-course dose may vary depending on the disease or condition being treated, and may also vary depending on the route of administration and treatment regimen.

[0230] Pharmaceutical compositions containing pharmaceutical agents can be formulated in a manner suitable for delivery methods using techniques conventionally practiced in the art. The compositions can be in the form of solids (e.g., tablets, capsules), semi-solids (e.g., gels), liquids, or gases (e.g., aerosols). In other embodiments, the pharmaceutical composition is administered by bolus infusion.

[0231] In the pharmaceutical field, pharmaceutically acceptable excipients are well-known, and, for example, Rowe et al., Handbook of Pharmaceutical Excipients: A Comprehensive Guide to Uses, Properties, and Safety, 5th Edition, 2006 and Remington: The Science and Practice of Pharmacy As described in (Gennaro, 21st edition Mack Pub. Co., Easton, PA (2005)). Exemplary pharmaceutically acceptable excipients include sterile saline and phosphate-buffered saline at physiological pH. Preservatives, stabilizers, dyes, buffers, etc., may be provided in the pharmaceutical composition. Additionally, antioxidants and suspending agents may be used. Generally, the choice of excipient type is based on the route of administration and the chemical composition of the active ingredient. Alternatively, the compositions described herein may be formulated as lyophilized products. The compositions described herein may be formulated into lyophilized products using one or more suitable excipient solutions, either lyophilized or otherwise, for use in dissolving and / or diluting the pharmaceutical composition upon administration. In other embodiments, the pharmaceutical agent may be encapsulated in liposomes using techniques known and practiced in the art. In certain specific embodiments, the pharmaceutical agent is not formulated in liposomes for application to stents treating highly (but not completely) occluded arteries. Pharmaceutical compositions may be formulated for any suitable route of administration described herein and in the art.

[0232] Pharmaceutical compositions, such as those for oral administration or injection, infusion, subcutaneous delivery, intramuscular delivery, intraperitoneal delivery, or other methods, may be in liquid form. Liquid pharmaceutical compositions may include one or more of the following: sterile diluents such as water, saline solution (preferably physiological saline), Ringer's solution, isotonic sodium chloride, non-volatile oils that can be used as solvents or suspension media, polyethylene glycol, glycerin, propylene glycol, or other solvents; antibacterial agents; antioxidants; chelating agents; buffers; and agents for regulating tension such as sodium chloride or dextran. Parenteral compositions may be packaged in ampoules, disposable syringes, or multi-dose vials made of glass or plastic. Physiological saline is preferred, and injectable pharmaceutical compositions are preferably sterile. In another embodiment, for the treatment of ophthalmic conditions or diseases, the liquid pharmaceutical composition may be administered to the eye as eye drops. The liquid pharmaceutical composition may be delivered orally.

[0233] For oral formulations, at least one of the pharmaceutical agents described herein can be used alone or in combination with suitable additives to form tablets, powders, granules, or capsules, and may be used in combination with diluents, buffers, wetting agents, preservatives, colorants, and flavoring agents, if desired. The pharmaceutical agent may be formulated with a buffer to provide protection of the compound from the low pH of the gastric environment and / or with enteric coating. Pharmaceutical agents included in the pharmaceutical composition may be formulated with flavoring agents (e.g., in liquid, solid, or semi-solid formulations) and / or with enteric coating for oral administration.

[0234] Pharmaceutical compositions comprising any of the agents described herein may be formulated as sustained-release or slow-release, also known as timed release or controlled release. Such compositions can generally be prepared using well-known techniques and administered via, for example, oral, rectal, intradermal, or subcutaneous implantation, or implantation at the desired target site. Sustained-release formulations may contain compounds dispersed in a carrier matrix and / or contained in a reservoir surrounded by a rate-controlled membrane. Excipients used in such formulations are biocompatible and may also be biodegradable; preferably, the formulation provides a relatively constant level of release of the active ingredient. The amount of agent contained in a sustained-release formulation depends on the implantation site, release rate, and expected duration, as well as the nature of the condition, disease, or ailment to be treated or prevented.

[0235] In some embodiments, the pharmaceutical composition containing the agent is formulated for transdermal, intradermal, or topical application. The composition can be applied using an applicator such as a syringe, bandage, transdermal patch, insert, or similar syringe in the form of powder / talcum powder or other solids, liquids, sprays, aerosols, ointments, foams, creams, gels, or pastes. This is preferably in the form of a controlled-release or sustained-release formulation, which is applied topically, for example, intradermally or subcutaneously, or injected directly into the skin adjacent to or within the area to be treated. The active composition can also be delivered via iontophoresis. Antiseptics can be used to prevent the growth of fungi and other microorganisms. Suitable antiseptics include, but are not limited to, benzoic acid, butylparaben, ethylparaben, methylparaben, propylparaben, sodium benzoate, sodium propionate, benzalkonium chloride, benzyl chloride, benzyl alcohol, cetylpyridinium chloride, chlorobutanol, phenol, phenethyl alcohol, thimerosal, and combinations thereof.

[0236] Pharmaceutical compositions containing pharmaceutical agents can be formulated into emulsions for topical application. The emulsion contains a liquid distributed in a second liquid. The emulsion can be an oil-in-water emulsion or an oil-in-water emulsion. Either or both of the oil and aqueous phases may contain one or more surfactants, emulsifiers, emulsion stabilizers, buffers, and other excipients. The oil phase may contain other pharmaceutically approved oily excipients. Suitable surfactants include, but are not limited to, anionic surfactants, nonionic surfactants, cationic surfactants, and amphoteric surfactants. Compositions for topical application may also include at least one suitable suspending agent, antioxidant, chelating agent, emollient, or moisturizing agent.

[0237] Ointments and creams can be formulated, for example, with an aqueous or oil-based base, in which suitable thickeners and / or gelling agents are added. Lotions can be formulated with an aqueous or oil-based base and generally also contain one or more emulsifiers, stabilizers, dispersants, suspending agents, thickeners, or colorants. Liquid sprays can be delivered by pressurized packaging, such as through specially shaped caps. Oil-in-water emulsions can also be used in compositions, patches, bandages, and articles. These systems are semi-solid emulsions, microemulsions, or foam emulsion systems.

[0238] In some embodiments, the pharmaceutical agents described herein can be formulated as inhalers. Inhalation methods can deliver the drug directly to the airways. The agents can be formulated as aerosols, microspheres, liposomes, or nanoparticles. The agents can be formulated with solvents, gases, nitrates, or any combination thereof. The compositions described herein are optionally formulated as liquid aerosols or inhalable dry powders for delivery. Liquid aerosol formulations are optionally primarily atomized into particle sizes that can be delivered to the terminal bronchioles and respiratory bronchioles. Liquid aerosols and inhalable dry powder formulations are preferably delivered through the entire bronchial canal to the terminal bronchioles and ultimately to the parenchymal tissue.

[0239] The aerosolized formulations described herein are optionally delivered using an aerosol-forming device (such as a jet injector, vibrating perforated plate, or ultrasonic nebulizer), preferably selected to allow the formation of aerosol particles with a median average diameter primarily between 1 and 5 μm. Furthermore, the formulation preferably has a balanced osmotic pressure ionic strength and chloride concentration, as well as a minimum aerosolizable volume capable of delivering an effective dose of the drug. Additionally, the aerosolized formulation preferably does not negatively affect airway function and does not cause undesirable side effects.

[0240] Suitable aerosol atomizing devices for administering the aerosol formulations described herein include, for example, jet atomizers, vibrating perforated plate atomizers, ultrasonic atomizers, and electrically powered dry powder inhalers, which are capable of atomizing the formulation into aerosol particles primarily in the 1-5 μm size range. The main intention of this application is that at least 70%, but preferably more than 90%, of all generated aerosol particles are in the 1-5 μm range. Jet atomizers operate by breaking a liquid solution into aerosol droplets using air pressure. Vibrating perforated plate atomizers operate by using an acoustic vacuum generated by a rapidly vibrating perforated plate to force solvent droplets through the perforated plate. Ultrasonic atomizers operate by shearing the liquid into small aerosol droplets using piezoelectric crystals. A variety of suitable devices are available, including, for example, AeroNeb... and AeroDose Vibrating multi-hole plate atomizer (AeroGen, Inc., Sunnyvale, California), Sidestream Nebulizer (Medic-Aid Ltd., West Sussex, England), Pari LC And Pari LC Star Jet atomizers (Pari Respiratory Equipment, Inc., Richmond, Virginia) and Aerosonic (DeVilbiss MedizinischeProdukte (Deutschland) GmbH, Heiden, Germany) and UltraAire (OmronHealthcare, Inc., Vernon Hills, Illinois) Ultrasonic nebulizer.

[0241] In some embodiments, the agent may be formulated with an oily matrix or ointment to form a semi-solid composition having the desired shape. In addition to the agent, these semi-solid compositions may contain a system of dissolved and / or suspended bactericides, preservatives, and / or buffers. The petrolatum component that may be included may be any paraffin wax with a viscosity ranging from mineral oils doped with isobutylene, colloidal silica, or stearates to paraffin wax. The absorbent matrix may be used with the oily system. Additives may include cholesterol, lanolin (lanolin derivatives, beeswax, fatty alcohols, lanolin alcohols, low HLB (hydrophobic-lipophilic balance) emulsifiers, and a variety of ionic and nonionic surfactants, alone or in combination.

[0242] Controlled-release or sustained-release transdermal or topical formulations can be achieved by adding gradually releasing additives (such as polymer structures and matrices) available in the art. For example, the composition can be administered using a hot-melt extruded article (such as a bioadhesive hot-melt extruded film). The formulation may contain a crosslinked polycarboxylic acid polymer formulation. The crosslinking agent may be present in an amount that provides sufficient adhesion to allow the system to remain attached to the surface of the target epithelial or endothelial cells for a sufficient time to allow the desired release of the compound.

[0243] Inserts, transdermal patches, bandages, or articles may contain polymer mixtures or coatings that provide a constant rate of drug release over a prolonged period of time. In some embodiments, the article, transdermal patch, or insert contains a water-soluble pore-forming agent, such as polyethylene glycol (PEG), which can be mixed with a water-insoluble polymer to increase the durability of the insert and prolong the release of the active ingredient.

[0244] Transdermal devices (insertions, patches, bandages) may also contain water-insoluble polymers. Rate-controlling polymers can be used to apply to sites where release can be influenced by pH variations. These rate-controlling polymers can be applied using a continuous coating film during the spraying and drying process with the active compound. In one embodiment, a coating formulation is used to coat pellets containing the active ingredient, which are compressed to form a solid, biodegradable insert.

[0245] Polymer formulations can also be used to provide controlled release or sustained release. Bioadhesive polymers described in the art can be used. By way of example, sustained-release gels and compounds can be incorporated into a polymer matrix, such as a hydrophobic polymer matrix. Examples of polymer matrices include microparticles. Microparticles can be microspheres, and the core can be a material different from the polymer shell. Alternatively, the polymer can be cast into a slab or film, produced as a powder or gel (such as a hydrogel) by milling or other standard techniques. Polymers can also be in the form of coatings or part of bandages, stents, catheters, vascular grafts, or other devices to facilitate drug delivery. The matrix can be formed by solvent evaporation, spray drying, solvent extraction, and other methods known to those skilled in the art.

[0246] Kits containing unit doses of one or more of the pharmaceutical agents described herein are typically supplied in oral or injectable doses. Such kits may include containers containing unit doses, informational inserts describing the use of the drug in treating diseases and associated benefits, and optionally, appliances or devices for delivering the composition.

[0247] Treatment In one aspect, this disclosure provides a method for treating a subject suffering from a tumor. In some cases, treatment of a subject suffering from a tumor includes administering to the subject a drug-connector or salt of formula (X), formula (XI), formula (XII), formula (XIII), formula (I), formula (IA), formula (Ia), formula (I-AAa), formula (Ib), formula (I-AAb), formula (IB), formula (II-A), or formula (II-B) (which further comprises a targeting unit), or a conjugate or salt of formula (XX), formula (XXI), formula (XXII), formula (XXIII), formula (A), formula (Aa), formula (Ab), formula (A-1), formula (A-2), formula (A-3), or formula (A-4), or a pharmaceutical composition thereof. In some cases, the tumor is associated with cancer. In some cases, the cancer is selected from lung cancer, kidney cancer, urethral cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, gastric cancer, and esophageal cancer. In some cases, the cancer is small cell lung cancer. In other cases, the cancer is large cell lung cancer.

[0248] In one aspect, this disclosure provides a method for treating a subject suffering from cancer. In some cases, treatment of a subject suffering from cancer includes administering to the subject a drug-connector or salt of formula (X), formula (XI), formula (XII), formula (XIII), formula (I), formula (IA), formula (Ia), formula (I-AAa), formula (Ib), formula (I-AAb), formula (IB), formula (II-A), or formula (II-B) (which further comprises a targeting unit), or a conjugate or salt of formula (XX), formula (XXI), formula (XXII), formula (XXIII), formula (A), formula (Aa), formula (Ab), formula (A-1), formula (A-2), formula (A-3), or formula (A-4), or a pharmaceutical composition thereof. In some cases, the tumor is associated with cancer. In some cases, the cancer is selected from lung cancer, kidney cancer, urethral cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, gastric cancer, and esophageal cancer. In some cases, the cancer is small cell lung cancer. In other cases, the cancer is large cell lung cancer.

[0249] In some embodiments, the compounds described herein can be used to treat diseases such as, but not limited to, hyperproliferative diseases, including: cancers of the head and neck, including tumors of the head, neck, nasal cavity, sinuses, nasopharynx, oral cavity, oropharynx, larynx, hypopharynx, salivary glands, and paragangliomas; cancers of the liver and biliary system, particularly hepatocellular carcinoma; colorectal cancer, particularly colorectal cancer; ovarian cancer; small cell and non-small cell lung cancer (SCLC and NSCLC); breast cancer sarcomas, such as fibrosarcoma, malignant fibrous histiocytoma, embryonal rhabdomyosarcoma, leiomyosarcoma, neurofibrosarcoma, and bone cancer. Sarcomas, synovial sarcomas, liposarcomas, and alveolar soft tissue sarcomas; leukemias such as acute promyelocytic leukemia (APL), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML); vegetations of the central nervous system, especially brain cancers; multiple myeloma (MM); lymphomas such as Hodgkin's lymphoma, lymphoplasmacytic lymphoma, follicular lymphoma, mucosa-associated lymphoid tissue lymphoma, mantle cell lymphoma, B-cell large cell lymphoma, Burkitt lymphoma, and T-cell anaplastic large cell lymphoma. Clinically, practice of the methods described herein and use of the compositions described herein will result in a reduction in the size or number of cancerous growths and / or a reduction in related symptoms (if applicable). Pathologically, practice of the methods described herein and use of the compositions described herein will produce pathology-related responses such as: inhibition of cancer cell proliferation, reduction of cancer or tumor size, prevention of further metastasis, and inhibition of tumor angiogenesis. A method for treating such diseases involves administering a therapeutically effective amount of the combination of the present invention to the subject. This method can be repeated as needed. The cancer may be kidney cancer, lung cancer, stomach cancer, or ovarian cancer.

[0250] In some embodiments, treatment of a tumor-bearing subject inhibits tumor growth by at least about 20%, more preferably at least about 40%, even more preferably at least about 60%, and even more preferably at least about 80%, relative to an untreated subject. The therapeutically effective amount of the therapeutic compound can reduce tumor size or otherwise improve symptoms in a subject, typically a human, but which may be another mammal.

[0251] In some embodiments, the compositions described herein may be administered in combination with other therapeutic agents, including antibodies, alkylating agents, angiogenesis inhibitors, antimetabolites, DNA cleaving agents, DNA cross-linking agents, DNA intercalating agents, DNA minor groove binding agents, enediyne, heat shock protein 90 inhibitors, histone deacetylase inhibitors, immunomodulators, microtubule stabilizers, nucleoside (purine or pyrimidine) analogs, nuclear export inhibitors, proteasome inhibitors, topoisomerase (I or II) inhibitors, tyrosine kinase inhibitors, and serine / threonine kinase inhibitors. Specific treatment agents include adalimumab, anserine P3, auripalatine, bendamustine, bevacizumab, bicalutamide, bleomycin, bortezomib, busulfan, callistatin A, camptothecin, capecitabine, carboplatin, carmustine, cetuximab, cisplatin, cladribine, cytarabine, cryptopycins, dacarbazine, dasatinib, daunorubicin, docetaxel, doxorubicin, duocarmycin, and dynemycin. A. Epotoxin, Etoposide, Fluorouracil, Fludarabine, 5-Fluorouracil, Gefitinib, Gemcitabine, Ipilimumab, Hydroxyurea, Imatinib, Infliximab, Interferon, Interleukin, β-Lapaquinone, Lenalidomide, Irinotecan, Maytansine, Nitrogen Mustard, Melphalan, 6-Mercaptopurine, Methotrexate, Mitomycin C, Nilotinib, Oxaliplatin, Paclitaxel, Procarbazine, S-saturated aniline (SAHA), 6-Thioguanidine, Thiotepa, Teniposide, Topotecan, Trastuzumab, Trichostatin A, Vincristine, Vincristine, and Vincristine.

[0252] Formulas (X), (XI), (XII), (XIII), (I), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (IB), (II-A), (II-B), (II-C), (II-D), (II-E), and (II-F) drug-connectors or salts, or formulas (XX), (XXI), (XXII), (XXIII), (A), (Aa), (Ab), (A-1), (A-2), (A-3), (A-4), (A-5), or (A-6) conjugates or salts, can be used to prepare medicaments for the prevention or treatment of diseases or conditions. Furthermore, methods for treating any disease or condition described herein in a subject requiring such treatment involve administering to said subject a therapeutically effective amount of a pharmaceutical composition containing at least one compound described herein, or a pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically acceptable solvate thereof.

[0253] The formulas (X), (XI), (XII), (XIII), (I), (IA), (Ia), (I-AAa), (Ib), (I-AAb), (I-AA), (I-AB), (IB), (II-A), (II-B), (II-C), (II-CA), (II-D), (II-E), (II-F), and (II-G) described herein are drug-connectors or salts, or formulas (XX), (XXI), (XXII), and (XXI... II) Conjugates or salts of formulas (A), (Aa), (Ab), (A-1), (A-2), (A-3), (A-4), (A-5), or (A-6) may be applied for prophylactic and / or therapeutic treatment. In therapeutic use, the composition is administered to a patient with an existing disease or condition in an amount sufficient to cure or at least partially relieve the symptoms of that disease or condition. The effective amount for this purpose will depend on the severity and course of the disease or condition, prior treatment, the patient's health status, weight, response to the drug, and the judgment of the attending physician.

[0254] In prophylactic use, compositions containing the compounds described herein are administered to patients who are susceptible to or at risk of developing a particular disease, condition, or illness. Such amounts are defined as “preventively effective amounts or doses.” In this use, the precise amount also depends on the patient’s health condition, weight, etc. When used on a patient, the effective amount for this purpose will depend on the severity and duration of the disease, condition, or illness, prior treatment, the patient’s health condition and response to the medication, and the judgment of the attending physician.

[0255] If the patient's condition does not improve, the compound may be used for a long period of time, including throughout the patient's life, in order to improve or otherwise control or limit the symptoms of the patient's disease or condition, as determined by the physician.

[0256] Once the patient's condition has improved, a maintenance dose may be administered if necessary. Subsequently, the dose or frequency of administration may be reduced, or both, depending on symptoms, until the disease, symptom, or condition has improved and remained at a certain level. However, the patient may require long-term basal intermittent therapy in case of any symptom recurrence.

[0257] The amount of a given drug corresponding to this quantity will vary depending on a variety of factors, such as the specific compound, the disease or condition and its severity, the identity of the person or host requiring treatment (e.g., weight), but can still be determined in a manner recognized in the art based on the specific circumstances surrounding the case, including, for example, the specific drug administered, the route of administration, the condition being treated, and the person or host being treated. However, in general, the dosage for adult treatment is typically in the range of about 0.02 to about 5000 mg per day, and in some embodiments, about 1 to about 1500 mg per day. The desired dosage can be conveniently administered as a single dose or in divided doses simultaneously (or over short periods of time) or at appropriate intervals, such as twice, three, four, or more times per day.

[0258] The pharmaceutical compositions described herein can be presented in unit dosage forms suitable for single, precise dosing. In a unit dosage form, the formulation is divided into unit doses containing appropriate amounts of one or more compounds. The unit dose can be in the form of a package containing discrete amounts of the formulation. Non-limiting examples include packaged tablets or capsules, and powders in vials or ampoules. Aqueous suspension compositions can be packaged in single-dose, non-resealable containers. Alternatively, multi-dose, resealable containers can be used, in which case preservatives are typically included in the composition. By way of example only, formulations for parenteral injection can be presented in unit dosage forms, including but not limited to ampoules or multi-dose containers in which preservatives are added.

[0259] The toxicity and efficacy of such treatment regimens can be determined through standard pharmaceutical procedures in cell culture or laboratory animals, including but not limited to determining the LD50. 50 (The dose that causes 50% lethality in the population) and ED 50 (The dose that makes 50% of the population therapeutically effective). The dose ratio between toxicity and therapeutic effect is the therapeutic index, which can be expressed as LD50. 50 With ED 50The ratio between them. Compounds exhibiting a high therapeutic index are preferred. Data obtained from cell culture assays and animal studies can be used to determine the dosage range for human use. The dosage of such compounds is preferably within the range including ED. 50 Furthermore, the concentration range with the lowest toxicity is within this range. The dosage can vary within this range depending on the dosage form and route of administration used.

[0260] In some embodiments, the present invention provides a method for treating or preventing a disease, state, or condition in a patient in need, comprising administering to the patient an effective amount of a compound of any embodiment of the present invention or a pharmaceutically acceptable salt thereof. The disease, state, or condition may be selected from the group described elsewhere herein.

[0261] Preparation of the drug-connector and conjugate disclosed herein The connectors, drug-connectors, and conjugates disclosed herein can generally be prepared in a variety of ways well known to those skilled in the art of organic synthesis.

[0262] In some embodiments, the linkers, drug-linkers, and conjugates of this disclosure can be synthesized using the methods described herein, as well as synthetic methods known in the field of synthetic organic chemistry or variations thereof as understood by those skilled in the art. In some embodiments, the conjugates can be prepared via several pathways employing organic chemical reactions, conditions, and reagents known to those skilled in the art, including: (1) the reaction of a nucleophilic group of a targeting unit (e.g., an antibody or its antigen-binding moiety or a non-antibody protein scaffold) with a divalent linker to form a targeting unit-linker intermediate via covalent bonding, followed by a reaction with a drug; and (2) the reaction of a nucleophilic group of a drug with a divalent linker to form a drug-linker via covalent bonding, followed by a reaction with a nucleophilic group of a targeting unit.

[0263] In some embodiments, techniques for attaching a drug to a target unit (such as an antibody or its antigen-binding portion or a non-antibody scaffold) via a connector can be used. In some cases, the connector is first attached to the drug (e.g., a cytotoxic agent, immunomodulator, or other agent), and then the drug-connector is attached to the target unit (e.g., an antibody or its antigen-binding portion or a non-antibody protein scaffold). In other cases, the connector is first attached to the target unit (e.g., an antibody or its antigen-binding portion or a non-antibody protein scaffold), and then the drug is attached to the connector.

[0264] In some implementations, the drug is attached to the target unit via a connector to reduce drug activity until it is released from the conjugate (e.g., by hydrolysis, by protein hydrolysis or by a cleavage agent).

[0265] In some embodiments, the nucleophilic groups on the targeting units, such as antibodies, antigen-binding moieties, and other binders (including non-antibody scaffolds), include, but are not limited to: (i) N-terminal amine groups, (ii) side-chain amine groups, such as lysine, (iii) side-chain thiol groups, such as cysteine, and (iv) glycosyl or amino groups, wherein the antibody is glycosylated. The amine, thiol, and hydroxyl groups are nucleophilic and capable of reacting with electrophilic groups on the linker to form covalent bonds, including: (i) active esters such as NHS esters, HOBt esters, halocarboxylate esters, and acid halides; (ii) alkyl and benzyl halides such as haloacetamides; and (iii) aldehyde, ketone, carboxyl, and maleimide groups. In some cases, the targeting units, such as antibodies (and antigen-binding moieties and other binders, including non-antibody scaffolds), have reducible interchain disulfides, i.e., cysteine ​​bridges. In some cases, treatment with reducing agents such as DTT (dithiothreitol) or TCEP (tricarbonylethylphosphine) can make antibodies (and antigen-binding moieties and other binders, including non-antibody scaffolds) reactive for conjugation with linkers or drug-linkers, thereby completely or partially reducing the antibody. In some cases, theoretically, each cysteine ​​bridge will thus form two reactive thiol nucleophiles. In some cases, additional nucleophilic groups can be introduced into targeting units such as antibodies (and antigen-binding moieties and other binders, including non-antibody scaffolds) by modifying lysine residues (e.g., by reacting lysine residues with 2-iminothiacyclopentane (Traut's reagent), resulting in the conversion of the amine to a thiol. In some cases, reactive thiol groups can also be introduced into targeting units (such as antibodies and antigen-binding moieties and other binders, including non-antibody scaffolds) by introducing one, two, three, four, or more cysteine ​​residues (e.g., by preparing antibodies, antigen-binding moieties, and other binders, including non-antibody scaffolds) containing one or more non-natural cysteine ​​amino acid residues).

[0266] In some embodiments, conjugates can also be generated by a reaction between an electrophilic group (such as an aldehyde or ketone carbonyl group) on the targeting unit and a nucleophilic group on the linker or drug-linker. In some cases, useful nucleophilic groups on the linker reagent include, but are not limited to, acylhydrazides, oximes, amino groups, hydrazides, thioureas, hydrazide carboxyl groups, and aryl acylhydrazides. In some cases, the antibody (or its antigen-binding moiety or other binding agent, including non-antibody scaffolds) is modified to introduce an electrophilic portion capable of reacting with nucleophilic substituents on the linker or drug-linker. In some cases, the sugar of a glycosylated antibody can be oxidized (e.g., with a periodate oxidant) to form an aldehyde or ketone group, which can react with the amine group on the linker or drug-linker. In some cases, the resulting imine Schiff base group can form a stable bond or can be reduced, for example, by a borohydride reagent, to form a stable amine bond. In some cases, the reaction of the carbohydrate portion of a glycosylated antibody with galactose oxidase or sodium periodate can produce carbonyl (aldehyde and ketone) groups in the antibody (or its antigen-binding portion or other binding agents, including non-antibody scaffolds) that can react with appropriate groups on the linker or drug-linker (see, for example, Hermanson, Bioconjugate Techniques).

[0267] In some embodiments, exemplary nucleophilic groups on a drug such as a cytotoxic agent include, but are not limited to: amine, mercapto, hydroxyl, acylhydrazine, oxime, hydrazine, thiourea, hydrazine carboxyl, and aryl acylhydrazine groups, which are capable of reacting with electrophilic groups on the linker to form covalent bonds, said electrophilic groups including: (i) active esters such as NHS esters, HOBt esters, halocarbamates, and acid halides; (ii) alkyl and benzyl halides such as haloacetamides; and (iii) aldehyde, ketone, carboxyl, and maleimide groups, ultimately forming a drug-linker or conjugate.

[0268] In some embodiments, the linker or drug-linker attaches to an interchain cysteine ​​residue of the antibody (or its antigen-binding moiety or other binding agent, including non-antibody scaffolds). In some cases, the linker or drug-linker typically contains a maleimide group for attachment to the cysteine ​​residue of the interchain disulfide. In some cases, the linker or drug-linker attaches to a cysteine ​​residue of the antibody or its antigen-binding moiety.

[0269] In some cases, drug connectors are selected from , and Each drug linker can be conjugated to either the UC-961 antibody or the ROR2 antibody under appropriate conditions.

[0270] The compounds disclosed herein can be prepared according to the schemes and examples described elsewhere herein.

[0271] The following embodiments further illustrate the present invention, but should not be construed as limiting its scope in any way.

[0272] Example The following synthetic schemes are provided for illustrative purposes and not for limitation. The following examples illustrate various methods for preparing the compounds described herein. It should be understood that those skilled in the art can prepare these compounds by similar methods or by combining other methods known to them. It should also be understood that those skilled in the art will be able to prepare them in a similar manner as described below by using appropriate starting materials and modifying the synthetic route as needed. In general, starting materials and reagents can be obtained from commercial suppliers or synthesized from sources known to those skilled in the art or prepared as described herein. The following abbreviations used below and throughout this specification are to be understood to have the following meanings unless otherwise indicated:

[0273] Preparation of drug junction Example 1: Synthesis of drug-connector compound 18 Compounds 6 and 14 were prepared as shown in schemes 1 and 2, and coupled as shown in scheme 3 to provide drug-connector 18.

[0274] Option 1

[0275] To a solution of Fmoc-Gly6-COOH (1, synthesized on Cl-Trt resin using the standard Fmoc SPPS procedure, 116 mg, 0.2 mmol) and compound 2 (HCl salt, 40 mg, 0.2 mmol) in anhydrous DMSO (4 mL), HOAt (28 mg, 0.2 mmol) and EDC.HCl (115 mg, 0.6 mmol) were added, followed by DIEA (0.07 mL). The mixture was stirred at room temperature for 4 h. Water (30 mL) was added, and the precipitate was collected by filtration. The resulting white solid was washed with water (10 mL x 2) and dried under vacuum to give crude Fmoc-Gly7-OBn, which was dissolved in DMF (4 mL). Piperidine (0.2 ...

Claims

1. A type (X) drug-connector: Formula (X) Or its pharmaceutically acceptable salt, wherein; R 40 Independently selected from hydrogen, Y and ; D is selected from the drug unit; n is selected from 0 and 1; m is selected from 0 and 1; Where at least n or m is 1; p is selected from 0 and 1; z is selected from 0 and 1; X is selected from CH and N; Y is selected from -OT 1 and -NH-T 2 ; T 1 For sugar-cuttable units; T 2 It is a peptide cleavable unit; S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, wherein the C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, wherein the C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 3 Selected from spacer regions, wherein the spacer regions are preferably phenylene, wherein S 3 To indicate whether something exists or does not exist; S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement; Where M 1 K 1 K 2 S 1 S 2 S 3 and S 4 The optional substituents on the surface are selected independently each time they appear: (i) Halogen, -OR 30 , -N(R 30 )2, -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -O-S(O)2OR 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ) and -CN; (ii) C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles; and (iii) C 3-10 A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group; M 1 These are groups that can react with ligands to form linker units; K 1 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; wherein when X is CH, D is eczema or MMAE, m is 1, n is 0, and K 1 The polysarcosine contains 2-9 sarcosine residues or 13-30 sarcosine residues; K 2 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and Each R 30 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles.

2. The drug-connector or salt as claimed in claim 1, wherein formula (X) is represented as follows: Formula (XI) or Formula (XII) Or its pharmaceutically acceptable salt.

3. The drug-connector or salt as described in claim 1, wherein formula (X) is represented as follows: Formula (XIII) Or its pharmaceutically acceptable salt.

4. The drug-connector or salt as described in claim 1 or 3, wherein formula (X) or formula (XIII) is represented as Formula (I) Or its pharmaceutically acceptable salt.

5. The drug-connector or salt as described in claim 4, wherein formula (I) is represented as follows: Formula (IA) Or its pharmaceutically acceptable salt.

6. The drug-connector or salt as described in claim 4, wherein formula (I) is represented as Formula (II-C) Or its pharmaceutically acceptable salt.

7. The drug-connector or salt as claimed in claim 4, wherein formula (I) is represented as Equation (II-D) Or its pharmaceutically acceptable salt.

8. The drug-connector or salt according to any one of claims 1 to 7, wherein S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replace.

9. The drug-connector or salt according to any one of claims 1 to 8, wherein S 1 Selected from: (i) optional substituted C6-C 10 Alkylene, wherein the C6-C 10 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )- or -C(O)- substitution.

10. The drug-connector or salt according to any one of claims 1 to 9, wherein S 1 It is a branched alkylene group.

11. The drug-connector or salt as claimed in any one of claims 1 to 10, S 1 Represented as .

12. The drug-connector or salt according to any one of claims 1 to 11, wherein S 2 Selected from: (i) optional substitutions of C8-C 12 Alkylene, wherein the C8-C 12 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 Replace with -, -O- and -C(O)-.

13. The drug-connector or salt according to any one of claims 1 to 12, wherein S 2 It is a linear alkylene group.

14. The drug-connector or salt as claimed in any one of claims 1 to 13, S 2 Represented as .

15. The drug-connector or salt as claimed in claim 10, wherein formula (I) is represented as Formula (IB) Or its pharmaceutically acceptable salt.

16. The drug connector or salt as claimed in any one of claims 1 to 5, wherein X is CH.

17. The drug connector or salt as claimed in any one of claims 1 to 5, wherein X is N.

18. The drug-connector or salt as claimed in any one of claims 1 to 5, wherein S 3 It exists and is a phenylene oxide.

19. The drug-connector or salt as claimed in any one of claims 1 to 5, wherein S 3 It does not exist.

20. The drug-connector or salt according to any one of claims 1 to 19, wherein each K 1 Selected from peptide units.

21. The drug-connector or salt of claim 20, wherein K 1 The peptide unit has 1 to 50 amino acids.

22. The drug-connector or salt of claim 21, wherein K 1 The amino acids mentioned are selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-alanine.

23. The drug-connector or salt of claim 21, wherein K 1 The amino acids mentioned are selected from glycine, sarcosine, proline, serine, alanine, and β-alanine.

24. The drug-connector or salt according to any one of claims 1 to 23, wherein K 1 The peptide unit has a terminal unit.

25. The drug-connector or salt according to any one of claims 1 to 24, wherein K 1 Selected from 、 、 、 、 、 、 、 The end unit is denoted as R 6 And each j is selected from 1 to 30.

26. The drug-connector or salt of claim 25, wherein R 6 Selected from -OR 7 and -NHR 7 , where R 7 Selected from hydrogen; C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3 to 10-membered heterocycles.

27. The drug-connector or salt as described in claim 25 or 26, wherein R 6 Selected from -OH, -NH2 and .

28. The drug-connector or salt according to any one of claims 1 to 27, wherein K 1 Selected from 、 、 、 、 , , and .

29. The drug-connector or salt according to any one of claims 1 to 28, wherein K 1 for .

30. The drug-connector or salt according to any one of claims 1 to 28, wherein K 1 for 。 31. The drug-connector or salt according to any one of claims 1 to 28, wherein K 1 for 。 32. The drug-connector or salt according to any one of claims 1 to 28, wherein K 1 for .

33. The drug-connector or salt according to any one of claims 1 to 28, wherein K 1 for .

34. The drug-connector or salt according to any one of claims 1 to 28, wherein K 1 for .

35. The drug-connector or salt as described in claim 6 or 7, wherein K 1 for .

36. The drug-connector or salt according to any one of claims 1 to 9 or 12 to 19, wherein S 1 Represented as .

37. The drug-connector or salt according to any one of claims 1 to 36, wherein each K 1 Selected from: Oligosaccharides.

38. The drug-connector or salt of claim 37, wherein each K 1 Selected from: and .

39. The drug-connector or salt as described in claim 1 or 3 to 4, wherein the formula is expressed as Formula (II-A) Or its pharmaceutically acceptable salt.

40. The drug-connector or salt as described in claims 1 or 3 to 4, wherein the formula is expressed as Formula (II-B) Or its pharmaceutically acceptable salt.

41. The drug-connector or salt as claimed in claim 1, wherein formula (X) is represented as Formula (II-G) Or its pharmaceutically acceptable salt.

42. The drug-connector or salt according to any one of claims 39 to 41, wherein S 1 Selected from: (i) optionally substituted C1-C2 alkylene groups, wherein one or more alkylene units of the C1-C2 alkylene group are optionally and independently converted to -N(R 20 )-replace.

43. The drug-connector or salt of claim 42, wherein S 1 Represented as .

44. The drug-connector or salt according to any one of claims 39 to 43, wherein S 2 Selected from: (i) optional substitutions of C8-C 12 Alkylene, wherein the C8-C 12 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 Replace with -, -O- and -C(O)-.

45. The drug-connector or salt of claim 44, wherein S 2 It is a linear alkylene group.

46. ​​The drug-connector or salt as described in claim 45, S 2 Represented as .

47. The drug-connector or salt as claimed in claim 1 or any one of 39 to 46, S 1 -S 2 Represented as .

48. The drug-connector or salt as claimed in claim 1 or any one of 39 to 47, S 1 -S 2 -M 1 Represented as S 3 It does not exist.

49. The drug-connector or salt according to any one of claims 1 to 14 or 16 to 47, wherein M 1 Selected from maleimide, halogen, COOH, azides Activated Groups, , OH, SH, activated disulfide groups, NH2 and -ONH2, preferably .

50. The drug-connector or salt of claim 49, wherein the activated Groups are selected from , and .

51. The drug-connector or salt of claim 49, wherein the activated disulfide group is selected from... and .

52. The drug-connector or salt according to any one of claims 39 to 47 or 49 to 51, wherein S 3 It exists and is a phenylene oxide.

53. The drug-connector or salt according to any one of claims 39 to 47 or 49 to 51, wherein S 3 It does not exist.

54. The drug-connector or salt as claimed in claim 4, wherein formula (I) is represented as Formula (II-E) Or its pharmaceutically acceptable salt.

55. The drug-connector or salt as claimed in claim 4, wherein formula (I) is represented as Formula (II-F) Or its pharmaceutically acceptable salt.

56. The drug connector or salt according to any one of claims 39 to 55, wherein p is 1.

57. The drug-connector or salt as claimed in claim 1 or any one of claims 39 to 56, wherein S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 Replace with -, -O-, or -C(O)-.

58. The drug-connector or salt as claimed in claim 1 or any one of claims 39 to 57, wherein S 4 Selected from: (i) optionally substituted C1-C5 alkylene groups, wherein one or more alkylene units of the C1-C5 alkylene group are optionally and independently converted to -N(R 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 Replace with -, -O-, or -C(O)-.

59. The drug-connector or salt as claimed in claim 1 or any one of 39 to 58, wherein S 4 Selected from: (i) optionally substituted C1-C3 alkylene groups, wherein one or more alkylene units of the C1-C5 alkylene groups are optionally and independently replaced by -N(H)-, -N(CH3)-, -O- or -C(O)-.

60. The drug-connector or salt as claimed in claim 1 or any one of claims 39 to 59, wherein S 4 Selected from , and .

61. The drug-connector or salt as claimed in claim 1 or any one of claims 39 to 59, wherein S 4 for .

62. The drug-connector or salt as claimed in claim 1 or any one of claims 39 to 59, wherein S 4 for .

63. The drug-connector or salt as claimed in claim 1 or any one of claims 39 to 59, wherein S 4 for .

64. The drug-connector or salt as claimed in claim 1 or any one of claims 39 to 63, wherein each K 2 Selected from peptide units.

65. The drug-connector or salt of claim 64, wherein K 2 The peptide unit has 1 to 50 amino acids.

66. The drug-connector or salt of claim 65, wherein K 2 The amino acids mentioned are selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-alanine.

67. The drug-connector or salt of claim 66, wherein K 2 The amino acids mentioned are selected from glycine, sarcosine, proline, serine, alanine, and β-alanine.

68. The drug-connector or salt according to any one of claims 39 to 67, wherein K 2 The peptide unit has a terminal unit.

69. The drug-connector or salt according to any one of claims 39 to 68, wherein K 2 Selected from , , , , , The end unit is denoted as R 6 And each j is selected from 1 to 30.

70. The drug-connector or salt of claim 69, wherein R 6 Selected from -OR 7 and -NHR 7 , where R 7 Selected from hydrogen; C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3 to 10-membered heterocycles.

71. The drug-connector or salt as described in claim 1, 69, or 70, wherein R 6 Selected from -OH, -NH2 and .

72. The drug-connector or salt as claimed in claim 1 or any one of claims 39 to 71, wherein K 2 Selected from , , , , , and .

73. The drug-connector or salt as claimed in claim 1 or any one of claims 39 to 71, wherein K 2 Selected from , , , , and .

74. The drug-connector or salt as claimed in claim 1 or any one of 39 to 70, wherein K 2 for .

75. The drug-connector or salt as claimed in claim 1 or any one of claims 39 to 70, wherein K 2 for .

76. The drug-connector or salt as claimed in claim 1 or any one of 39 to 70, wherein K 2 for 。 77. The drug-connector or salt as claimed in claim 1 or any one of claims 39 to 70, wherein K 2 for 。 78. The drug-connector or salt as claimed in claim 1 or any one of claims 39 to 70, wherein K 2 for 。 79. The drug-connector or salt as claimed in claim 1 or any one of 39 to 70, wherein K 2 for 。 80. The drug-connector or salt as claimed in claim 1 or any one of claims 39 to 70, wherein K 2 for 。 81. The drug-connector or salt as claimed in any one of claims 1 or 39 to 70, wherein K 2 Selected from: Oligosaccharides.

82. The drug-connector or salt of claim 81, wherein each K 2 Selected from: and , where k is selected from 2 to 10.

83. The drug-connector or salt of claim 82, wherein each K 2 Selected from: and .

84. The drug-connector or salt according to any one of claims 1 to 83, wherein T 1 The sugar-cuttable unit comprises sugar.

85. The drug connector or salt according to any one of claims 1 to 84, wherein the sugar is glucuronic acid.

86. The drug-connector or salt according to any one of claims 1 to 85, wherein Y is .

87. The drug-connector or salt according to any one of claims 1 to 83, wherein T 2 The peptide unit comprises one or more amino acids selected from the following: alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-alanine.

88. The drug-connector or salt of claim 87, wherein T 2 The peptide units mentioned above include dipeptides or tripeptides.

89. The drug-connector or salt of claim 88, wherein T 2 The peptide unit comprises a dipeptide.

90. The drug-connector or salt of any one of claims 89, wherein the dipeptide is selected from Val-Cit, Val-Ala, and Phe-Lys.

91. The drug-connector or salt according to any one of claims 1 to 87 to 90, wherein T 2 The peptide unit includes a capped portion.

92. The drug-connector or salt of claim 91, wherein the sealing end is divided into .

93. The drug-connector or salt according to any one of claims 87 to 92, wherein Y is .

94. The drug-connector or salt of any one of claims 1 to 93, wherein D is selected from cytotoxic agents, immunomodulators, nucleic acids, growth inhibitors, PROTACs, toxins, radioisotopes, and chelating ligands.

95. The drug connector or salt according to any one of claims 1 to 94, wherein D is selected from cytotoxic agents and immunomodulators.

96. The drug connector or salt of any one of claims 1 to 95, wherein D is selected from eczema and monomethylauratestatin E (MMAE).

97. The drug connector or salt according to any one of claims 1 to 96, wherein D is eczema.

98. A conjugate comprising a drug-connector or salt as claimed in any one of claims 1 to 97, and a targeting unit, wherein the M of the drug-connector 1 It reacts with the target unit and forms a covalent bond with it.

99. The conjugate of claim 98, wherein the targeting unit is selected from an antibody or its antigen-binding portion.

100. The conjugate of claim 98 or 99, wherein the average ratio of drug-connector to target unit is about 1 to 10.

101. A pharmaceutical composition comprising a conjugate as described in any one of claims 98 to 100 and a pharmaceutically acceptable excipient.

102. A method of treating a subject suffering from cancer, comprising administering to the subject in need the conjugate as claimed in claim 98 or the pharmaceutical composition as claimed in claim 101.

103. A conjugate of formula (XX): Formula (XX) Or its pharmaceutically acceptable salt, wherein; R 40 Independently selected from hydrogen, Y and ; D is selected from the drug unit; n is selected from 0 and 1; m is selected from 0 and 1; Where at least n or m is 1; p is selected from 0 and 1; z is selected from 0 and 1; X is selected from CH and N; Y is -OT 1 and -NH-T 2 ; T 1 For sugar-cuttable units; T 2 It is a peptide cleavable unit; S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, wherein the C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, wherein the C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 3 Selected from spacer regions, wherein the spacer regions are preferably phenylene, wherein S 3 To indicate whether something exists or does not exist; S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement; Where M 2 K 1 K 2 S 1 S 2 S 3 and S 4 The optional substituents on the surface are selected independently each time they appear: (i) a halogen, -OR 30 , -N(R 30 )2, -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -O-S(O)2OR 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ) and -CN; (ii) C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles; and (iii) C 3-10 A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group; L represents the target unit; M 2 For connection units; K 1 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; wherein when X is CH, D is eczema or MMAE, m is 1, n is 0, and K 1 The polysarcosine contains 2-9 sarcosine residues or 13-30 sarcosine residues; K 2 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and Each R 30 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles.

104. The conjugate or salt of claim 103, wherein formula (XX) is represented as follows: Formula (XXI) or Formula (XXII) Or its pharmaceutically acceptable salt.

105. The conjugate or salt as described in claim 103 or 104, wherein formula (XX) is represented as follows: Formula (XXIII) Or its pharmaceutically acceptable salt.

106. The conjugate or salt of claim 103, wherein formula (XX) is represented as follows: Formula (A) Or its pharmaceutically acceptable salt.

107. The conjugate or salt of claim 106, wherein formula (A) is represented as follows: Equation (A-1) Or its pharmaceutically acceptable salt.

108. The conjugate or salt as described in claim 103 or 107, wherein S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replace.

109. The conjugate or salt according to any one of claims 103 to 108, wherein S 1 Selected from: (i) optional substituted C6-C 10 Alkylene, wherein the C6-C 10 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )- or -C(O)- substitution.

110. The conjugate or salt according to any one of claims 103 to 109, wherein S 1 It is a branched alkylene group.

111. The conjugate or salt according to any one of claims 103 to 110, S 1 Represented as .

112. The conjugate or salt according to any one of claims 103 to 111, wherein S 2 Selected from: (i) optional substitutions of C8-C 12 Alkylene, wherein the C8-C 12 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 Replace with -, -O- and -C(O)-.

113. The conjugate or salt according to any one of claims 103 to 112, wherein S 2 It is a linear alkylene group.

114. The conjugate or salt according to any one of claims 103 to 113, S 2 Represented as 。 115. The conjugate or salt of claim 114, wherein formula (A) is represented as follows: Equation (A-2) Or its pharmaceutically acceptable salt.

116. The conjugate or salt of any one of claims 103 to 115, wherein X is CH.

117. The conjugate or salt of any one of claims 103 to 115, wherein X is N.

118. The conjugate or salt as described in claim 103 or 117, wherein S 3 It exists and is a phenylene oxide.

119. The conjugate or salt as described in claim 103 or 117, wherein S 3 It does not exist.

120. The conjugate or salt as described in claim 103 or 119, wherein each K 1 Selected from peptide units.

121. The drug-connector or salt of claim 120, wherein K 1 The peptide unit has 1 to 50 amino acids.

122. The drug-connector or salt of claim 121, wherein K 1 The amino acids mentioned are selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-alanine.

123. The drug-connector or salt of claim 122, wherein K 1 The amino acids mentioned are selected from glycine, sarcosine, proline, serine, alanine, and β-alanine.

124. The drug-connector or salt according to any one of claims 103 to 123, wherein K 1 The peptide unit has a terminal unit.

125. The drug-connector or salt according to any one of claims 103 to 124, wherein K 1 Selected from 、 、 、 、 、 The end unit is denoted as R 6 And each j is selected from 1 to 30.

126. The drug-connector or salt of claim 125, wherein R 6 Selected from -OR 7 and -NHR 7 , where R 7 Selected from hydrogen; C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3 to 10-membered heterocycles.

127. The drug-connector or salt as described in claim 125 or 126, wherein R 6 Selected from -OH, -NH2 and .

128. The drug-connector or salt according to any one of claims 103 to 127, wherein K 1 Selected from 、 、 , , and .

129. The drug-connector or salt according to any one of claims 103 to 128, wherein K 1 for .

130. The drug-connector or salt according to any one of claims 103 to 128, wherein K 1 for 。 131. The drug-connector or salt according to any one of claims 103 to 128, wherein K 1 for 。 132. The drug-connector or salt according to any one of claims 103 to 128, wherein K 1 for 。 133. The drug-connector or salt according to any one of claims 103 to 128, wherein K 1 for 。 134. The drug-connector or salt according to any one of claims 103 to 128, wherein K 1 for 。 135. The drug-connector or salt according to any one of claims 103 to 128, wherein K 1 for .

136. The drug-connector or salt according to any one of claims 103 to 107, wherein S 1 Represented as .

137. The drug-connector or salt as described in claims 103 to 107, 112 to 114, or 136, wherein each K 1 Selected from: Oligosaccharides.

138. The drug-connector or salt of claim 137, wherein each K 1 Selected from: and .

139. The conjugate or salt of claim 106, wherein formula (A) is represented as follows: Equation (A-3) Or its pharmaceutically acceptable salt.

140. The conjugate or salt of claim 106, wherein formula (A) is represented as follows: Equation (A-4) Or its pharmaceutically acceptable salt.

141. The conjugate or salt according to any one of claims 139 to 140, wherein S 1 Selected from: (i) optionally substituted C1-C2 alkylene groups, wherein one or more alkylene units of the C1-C2 alkylene group are optionally and independently converted to -N(R 20 )-replace.

142. The conjugate or salt of claim 141, wherein S 1 Represented as .

143. The conjugate or salt according to any one of claims 139 to 141, wherein S 2 Selected from: (i) optional substitutions of C8-C 12 Alkylene, wherein the C8-C 12 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 Replace with -, -O- and -C(O)-.

144. The conjugate or salt of claim 143, wherein S 2 It is a linear alkylene group.

145. The conjugate or salt according to any one of claims 139 to 144, S 2 Represented as 。 146. The conjugate or salt according to any one of claims 139 to 145, S 1 -S 2 Represented as 。 147. The conjugate or salt according to any one of claims 139 to 146, wherein M 2 Selected from , , , , and .

148. The conjugate or salt according to any one of claims 139 to 147, wherein M 2 for .

149. The conjugate or salt according to any one of claims 139 to 148, wherein S 3 It exists and is a phenylene oxide.

150. The conjugate or salt according to any one of claims 139 to 148, wherein S 3 It does not exist.

151. The conjugate or salt according to any one of claims 139 to 148, S 1 -S 2 -M 2 -L indicates that S 3 It does not exist.

152. The conjugate or salt of claim 106, wherein formula (A) is represented as follows: Equation (A-5) Or its pharmaceutically acceptable salt.

153. The conjugate or salt of claim 106, wherein formula (A) is represented as follows: Equation (A-6) Or its pharmaceutically acceptable salt.

154. The conjugate or salt of any one of claims 103, 105, 106 or 139 to 153, wherein p is 1.

155. The conjugate or salt according to any one of claims 103, 105, 106 or 139 to 154, wherein S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 Replace with -, -O-, or -C(O)-.

156. The conjugate or salt according to any one of claims 103, 105, 106 or 139 to 155, wherein S 4 Selected from: (i) optionally substituted C1-C5 alkylene groups, wherein one or more alkylene units of the C1-C5 alkylene group are optionally and independently converted to -N(R 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 Replace with -, -O-, or -C(O)-.

157. The conjugate or salt according to any one of claims 103, 105, 106 or 139 to 156, wherein S 4 Selected from: (i) optionally substituted C1-C3 alkylene groups, wherein one or more alkylene units of the C1-C5 alkylene groups are optionally and independently replaced by -N(H)-, -N(CH3)-, -O- or -C(O)-.

158. The conjugate or salt according to any one of claims 103, 105, 106 or 139 to 157, wherein S 4 Selected from , and .

159. The conjugate or salt according to any one of claims 103, 105, 106 or 139 to 158, wherein S 4 for .

160. The conjugate or salt of any one of claims 103, 105, 106 or 139 to 158, wherein S 4 for .

161. The conjugate or salt according to any one of claims 103, 105, 106 or 139 to 158, wherein S 4 for .

162. The conjugate or salt of any one of claims 103, 105, 106 or 139 to 161, wherein each K 2 Selected from peptide units.

163. The conjugate or salt of claim 162, wherein K 2 The peptide unit has 1 to 50 amino acids.

164. The conjugate or salt of claim 163, wherein K 2 The amino acids mentioned are selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-alanine.

165. The conjugate or salt of claim 164, wherein K 2 The amino acids mentioned are selected from glycine, sarcosine, proline, serine, alanine, and β-alanine.

166. The conjugate or salt according to any one of claims 139 to 165, wherein K 2 The peptide unit has a terminal unit.

167. The conjugate or salt of any one of claims 103, 105, 106, 130 to 166, wherein K 2 Selected from , , , , 、 、 、 The end unit is denoted as R 6 And each j is selected from 1 to 30.

168. The conjugate or salt of claim 167, wherein R 6 Selected from -OR 7 and -NHR 7 , where R 7 Selected from hydrogen; C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3 to 10-membered heterocycles.

169. The conjugate or salt of claim 167 or 168, wherein R 6 Selected from -OH, -NH2 and .

170. The conjugate or salt of any one of claims 103, 105, 106, or 139 to 169, wherein K 2 Selected from , , 、 、 、 , , and .

171. The conjugate or salt of any one of claims 103, 105, 106 or 139 to 169, wherein K 2 Selected from , 、 、 、 , , and .

172. The conjugate or salt according to any one of claims 103, 105, 106 or 139 to 171, wherein K 2 for .

173. The conjugate or salt according to any one of claims 103, 105, 106 or 139 to 171, wherein K 2 for .

174. The conjugate or salt according to any one of claims 103, 105, 106 or 139 to 171, wherein K 2 for .

175. The conjugate or salt of any one of claims 103, 105, 106 or 139 to 171, wherein K 2 for .

176. The conjugate or salt of any one of claims 103, 105, 106 or 139 to 171, wherein K 2 for .

177. The conjugate or salt of any one of claims 103, 105, 106 or 139 to 171, wherein K 2 for .

178. The conjugate or salt of any one of claims 103, 105, 106 or 139 to 171, wherein K 2 for .

179. The conjugate or salt of any one of claims 103, 105, 106 or 139 to 171, wherein K 2 Selected from: Oligosaccharides.

180. The conjugate or salt of claim 179, wherein each K 2 Selected from: and , where k is selected from 2 to 10.

181. The conjugate or salt of claim 180, wherein each K 2 Selected from: and .

182. The conjugate or salt according to any one of claims 103 to 181, wherein T 1 The sugar-cuttable unit comprises sugar.

183. The conjugate or salt of claim 182, wherein the sugar is glucuronic acid.

184. The conjugate or salt according to any one of claims 103 to 183, wherein Y is .

185. The conjugate or salt according to any one of claims 103 to 184, wherein T 2 The peptide unit comprises one or more amino acids selected from the following: alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, valine, citrulline, and β-alanine.

186. The conjugate or salt of claim 185, wherein T 2 The peptide units mentioned above include dipeptides or tripeptides.

187. The conjugate or salt of claim 186, wherein T 2 The peptide unit comprises a dipeptide.

188. The conjugate or salt of any one of claims 185 to 187, wherein the dipeptide is selected from Val-Cit, Val-Ala, and Phe-Lys.

189. The conjugate or salt according to any one of claims 185 to 188, wherein T 2 The peptide unit includes a capped portion.

190. The conjugate or salt of claim 189, wherein the capping end is divided into .

191. The conjugate or salt according to any one of claims 103 to 190, wherein Y is .

192. The conjugate or salt according to any one of claims 103 to 191, wherein M 2 for .

193. The conjugate or salt of any one of claims 103 to 192, wherein D is selected from cytotoxic agents, immunomodulators, nucleic acids, growth inhibitors, PROTACs, toxins, radioisotopes, and chelating ligands.

194. The conjugate or salt of any one of claims 103 to 193, wherein D is selected from cytotoxic agents and immunomodulators.

195. The conjugate or salt of any one of claims 103 to 193, wherein D is selected from eczetidine and monomethylauratestatin E (MMAE).

196. The conjugate or salt of any one of claims 103 to 195, wherein D is eczetidine.

197. The conjugate or salt according to any one of claims 103 to 195, wherein D is... .

198. The conjugate as claimed in claim 103, 105, or 106, wherein the conjugate is represented as Where L is the target unit; and DAR is the drug-to-antibody ratio.

199. The conjugate as claimed in claim 103, 105, or 106, wherein the conjugate is represented as Where L is the target unit; and DAR is the drug-to-antibody ratio.

200. The conjugate as claimed in claim 103, 105, or 106, wherein the conjugate is represented as Where L is the target unit; and DAR is the drug-to-antibody ratio.

201. The conjugate as claimed in claim 103, 105, or 106, wherein the conjugate is represented as Where L is the target unit; and DAR is the drug-to-antibody ratio.

202. The conjugate as claimed in claim 103, 105, or 106, wherein the conjugate is represented as Where L is the target unit; and DAR is the drug-to-antibody ratio.

203. The conjugate as claimed in claim 103, 105, or 106, wherein the conjugate is represented as Where L is the target unit; and DAR is the drug-to-antibody ratio.

204. The conjugate as claimed in claim 103, 105, or 106, wherein the conjugate is represented as Where L is the target unit; and DAR is the drug-to-antibody ratio.

205. The conjugate as claimed in claim 103, 105, or 106, wherein the conjugate is represented as Where L is the target unit; and DAR is the drug-to-antibody ratio.

206. The conjugate as claimed in claim 103, 105, or 106, wherein the conjugate is represented as Where L is the target unit; and DAR is the drug-to-antibody ratio.

207. The conjugate as claimed in claim 103, 105, or 106, wherein the conjugate is represented as Where L is the target unit; and DAR is the drug-to-antibody ratio.

208. The conjugate or salt of any one of claims 103 to 207, wherein the targeting unit is selected from an antibody or an antigen-binding fragment thereof.

209. The conjugate of any one of claims 98 to 208, wherein the targeting unit is a monoclonal antibody.

210. The conjugate of any one of claims 98 to 208, wherein the targeting unit comprises: a heavy chain comprising SEQ ID NO:1 and a light chain comprising SEQ ID NO:

2.

211. The conjugate according to any one of claims 98 to 208 or 210, wherein the targeting unit comprises: a heavy chain comprising SEQ ID NO:3 and a light chain comprising SEQ ID NO:

4.

212. The conjugate according to any one of claims 98 to 210, wherein the targeting unit is UC-961.

213. The conjugate according to any one of claims 98 to 209 or 211, wherein the targeting unit is a ROR2 antibody.

214. The conjugate of claim 208 or 209, wherein the antibody or its antigen-binding portion has a heavy chain, wherein the heavy chain is SEQ ID NO:1; and a light chain, wherein the light chain is SEQ ID NO:

2.

215. The conjugate of claim 208 or 209, wherein the antibody or its antigen-binding portion has a heavy chain, wherein the heavy chain is SEQ ID NO:3; and a light chain, wherein the light chain is SEQ ID NO:

4.

216. The conjugate of claim 208 or 209, wherein the antibody or its antigen-binding portion is UC-961.

217. The conjugate of claim 208 or 209, wherein the antibody or its antigen-binding portion is a ROR2 antibody.

218. The conjugate or salt of any one of claims 103 to 217, wherein the drug-to-target unit average ratio (DAR) is about 1 to about 10.

219. The conjugate or salt of any one of claims 103 to 218, wherein the drug-to-target ratio (DAR) is about 2 to about 8.

220. The conjugate or salt of any one of claims 103 to 198, wherein the drug-to-target ratio (DAR) is about 8.

221. A pharmaceutical composition comprising the conjugate as described in any one of claims 103 to 220 and a pharmaceutically acceptable excipient.

222. A method of treating a subject suffering from a disease or condition, comprising administering to the subject in need the conjugate as described in any one of claims 103 to 220 or the pharmaceutical composition as described in claim 221.

223. A method of treating a subject suffering from cancer, comprising administering to the subject in need the conjugate as described in any one of claims 103 to 220 or the pharmaceutical composition as described in claim 221.

224. A method of treating a subject suffering from a tumor, comprising administering to the subject in need the conjugate as described in any one of claims 103 to 220 or the pharmaceutical composition as described in claim 221.

225. The method of claim 224, wherein the tumor is associated with cancer.

226. Use of the conjugate for treating a person suffering from a disease or condition, including administering to the person in need the conjugate as described in any one of claims 103 to 220 or the pharmaceutical composition as described in claim 221.

227. The use as described in claim 226, wherein the disease or condition is cancer.

228. The method of claim 223, 225, or 227, wherein the cancer is selected from: cancers of the head and neck, including tumors of the head, neck, nasal cavity, sinuses, nasopharynx, oral cavity, oropharynx, larynx, hypopharynx, salivary glands, and paragangliomas; cancers of the liver and biliary system, particularly hepatocellular carcinoma; intestinal cancer, particularly colorectal cancer; ovarian cancer; small cell and non-small cell lung cancer (SCLC and NSCLC); breast cancer sarcomas, such as fibrosarcoma, malignant fibrous histiocytoma, embryonal rhabdomyosarcoma, leiomyosarcoma, neurofibrosarcoma, osteosarcoma, etc. Membrane sarcoma, liposarcoma, and alveolar soft tissue sarcoma; leukemias such as acute promyelocytic leukemia (APL), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML); vegetations of the central nervous system, especially brain cancer; multiple myeloma (MM); lymphomas such as Hodgkin's lymphoma, lymphoplasmacytic lymphoma, follicular lymphoma, mucosa-associated lymphoid tissue lymphoma, mantle cell lymphoma, B-cell large cell lymphoma, Burkitt lymphoma, and T-cell anaplastic large cell lymphoma.

229. The method of claim 223, 225 or 227, wherein the cancer is selected from cellular lymphoma, non-small cell lung cancer, large cell lung cancer, breast cancer and small cell lung cancer.

230. The method of claim 223, 225 or 227, wherein the cancer is a cell lymphoma.

231. The method of claim 223, 225 or 227, wherein the cancer is non-small cell lung cancer.

232. The method of claim 223, 225 or 227, wherein the cancer is large cell lung cancer.

233. The method of claim 223, 225 or 227, wherein the cancer is breast cancer.

234. The method of claim 223, 225 or 227, wherein the cancer is small cell lung cancer.

235. A drug-connector of type (Ia) or type (Ib): Formula (It), Formula (Ib) Or a pharmaceutically acceptable salt thereof, wherein; D is selected from the drug unit; n is selected from 0 and 1; m is selected from 0 and 1; Where at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is -OT 1 and -NH-T 2 ; T 1 For sugar-cuttable units; T 2 It is a peptide cleavable unit; S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, wherein the C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, wherein the C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 3 Selected from spacer regions, wherein the spacer regions are preferably phenylene, wherein S 3 To indicate whether something exists or does not exist; S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement; Where M 1 K 1 K 2 S 1 S 2 S 3 and S 4 The optional substituents on the surface are selected independently each time they appear: (i) Halogen, -OR 30 , -N(R 30 )2, -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -O-S(O)2OR 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ) and -CN; (ii) C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles; and (iii) C 3-10 A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group; M 1 These are groups that can react with ligands to form linker units; K 1 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; wherein when X is CH, D is eczema or MMAE, m is 1, n is 0, and K 1 The polysarcosine contains 2-9 sarcosine residues or 13-30 sarcosine residues; K 2 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and Each R 30 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles.

236. The drug-connector or salt of claim 235, wherein D is selected from cytotoxic agents, immunomodulators, nucleic acids, growth inhibitors, PROTACs, toxins, radioisotopes, and chelating ligands.

237. The drug-connector or salt of claim 235 or 236, wherein D is selected from cytotoxic agents and immunomodulators.

238. The drug connector or salt of any one of claims 235 or 236, wherein D is selected from eczema and monomethylauratestatin E (MMAE).

239. The drug connector or salt of any one of claims 235 to 238, wherein D is eczema.

240. The drug-connector or salt according to any one of claims 235 to 239, wherein the drug-connector is: 。 241. The drug-connector or salt according to any one of claims 235 to 239, wherein the drug-connector is: 。 242. A conjugate comprising a drug-connector or salt as claimed in any one of claims 235 to 241, and a targeting unit, wherein the M of the drug-connector 1 It reacts with the target unit and forms a covalent bond with it.

243. The conjugate of claim 242, wherein the targeting unit is selected from an antibody or its antigen-binding portion.

244. The conjugate of claim 242 or 243, wherein the average ratio of drug-connector to target unit is about 1 to 10.

245. The conjugate of claim 242 or 243, wherein the average ratio of drug-connector to target unit is 8.

246. A pharmaceutical composition comprising the conjugate as described in any one of claims 235 to 245 and a pharmaceutically acceptable excipient.

247. A method of treating a subject suffering from cancer, comprising administering to the subject in need the conjugate as described in claims 235 to 245 or the pharmaceutical composition as described in claim 246.

248. A conjugate, represented by formula (Aa) or formula (Ab): Formula (Aa), Formula (Ab) or Or its pharmaceutically acceptable salt, wherein; D is selected from the drug unit; n is selected from 0 and 1; m is selected from 0 and 1; Where at least n or m is 1; p is selected from 0 and 1; X is selected from CH and N; Y is -OT 1 and -NH-T 2 ; T 1 For sugar-cuttable units; T 2 It is a peptide cleavable unit; S 1 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, wherein the C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 2 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 (ii) Optional substitution of C3-C 30 alkenyl groups, wherein the C3-C 30 One or more alkenyl units of the alkenyl group are optionally and independently converted to -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 (iii) 2-substituted amino acids; (iv) one or more N-substituted amino acids; (v) optionally substituted polyethers; (vi) optionally substituted C3-C 10 Carbocyclic alkenes; (vii) optionally substituted 5- to 10-membered heterocyclic alkenes; S 3 Selected from spacer regions, wherein the spacer regions are preferably phenylene, wherein S 3 To indicate whether something exists or does not exist; S 4 Selected from: (i) optional substitutions of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 -, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2-, 5- to 6-membered heterocyclic alkenes or -P(O)(R 20 )2-Replacement; Where M 2 K 1 K 2 S 1 S 2 S 3 and S 4 The optional substituents on the surface are selected independently each time they appear: (i) Halogen, -OR 30 , -N(R 30 )2, -SR 30 , -N(R 30 )2, -C(O)R 30 , -C(O)N(R 30 )2, -N(R 30 )C(O)R 30 , -C(O)OR 30 , -OC(O)R 30 , -S(O)R 30 , -S(O)2R 30 , -O-S(O)2OR 30 , -P(O)(OR 30 )2, -OP(O)(OR 30 )2, -NO2, =O, =S, =N(R 30 ) and -CN; (ii) C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 Alkyne group, each of which is independently substituted with one or more of the following substituents: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -OS(O)2OR 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles; and (iii) C 3-10 A carbocyclic ring and 3 to 10-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OR 30 -SR 30 -N(R) 30 )2、-C(O)R 30 -C(O)N(R) 30 )2、-N(R 30 )C(O)R 30 -C(O)OR 30 -OC(O)R 30 -S(O)R 30 -S(O)2R 30 -P(O)(OR) 30 )2、-OP(O)(OR 30 )2、-NO2、=O、=S、=N(R 30 -CN, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group; L represents the target unit; M 2 For connection units; K 1 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; wherein when X is CH, D is eczema or MMAE, m is 1, n is 0, and K 1 The polysarcosine contains 2-9 sarcosine residues or 13-30 sarcosine residues; K 2 Selected from: (i) peptide units, (ii) Optional substitution of C1-C 30 Alkylene, wherein the C1-C 30 One or more alkylene units of an alkylene group are optionally and independently prefixed with -N(R) 20 )-、-N(R 20 )C(O)-、-C(O)N(R 20 )-、-N(R 20 S(O)2-、-S(O)2N(R) 20 )-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, -S(O)2- or -P(O)(R 20 )2-Replacement; (iii) Oligosaccharides; and (iv) Polyether; Each R 20 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles; and Each R 30 Independently selected from hydrogen; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 A carbocyclic ring and 3 to 12-membered heterocycles, each of which is independently substituted with one or more substituents selected from the following: halogen, -OH, -CN, -NO2, -NH2, -N(C 1-6 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, oxo, C 3-12 Carbon rings and 3 to 12-membered heterocycles.

249. The conjugate or salt of claim 248, wherein the targeting unit is selected from an antibody or its antigen-binding portion.

250. The conjugate or salt of claim 248 or 249, wherein the average ratio of drug-connector to target unit is about 1 to 10.

251. The conjugate or salt of claim 248 or 249, wherein the average ratio of drug-connector to target unit is about 8.

252. The conjugate or salt of claim 248, wherein the conjugate is represented as Where L is the target unit; and DAR is the drug-to-antibody ratio.

253. The conjugate or salt of claim 248, wherein the conjugate is represented as , where L is the target unit; and DAR is the ratio of drug to target unit.

254. The conjugate of any one of claims 248 to 253, wherein the targeting unit is an antibody or its antigen-binding portion.

255. A pharmaceutical composition comprising the conjugate as described in any one of claims 248 to 254 and a pharmaceutically acceptable excipient.

256. A method of treating a subject suffering from a disease or condition, comprising administering to the subject in need the conjugate as described in any one of claims 248 to 254 or the pharmaceutical composition as described in claim 255.

257. A method of treating a subject suffering from cancer, comprising administering to the subject in need the conjugate as described in any one of claims 248 to 254 or the pharmaceutical composition as described in claim 255.

258. Use of the conjugate for treating a person suffering from a disease or condition, including administering to the person in need the conjugate as described in any one of claims 248 to 254 or the pharmaceutical composition as described in claim 255.

259. A pharmaceutically acceptable salt of a conjugate of Table A or any of the conjugates thereof.

260. The conjugate or salt of claim 259, wherein the drug-to-target ratio (DAR) is about 1 to about 10.

261. The conjugate or salt of claim 259 or 260, wherein the drug-to-target unit average ratio (DAR) is about 8.

262. A pharmaceutical composition comprising the conjugate as described in any one of claims 259 to 261 and a pharmaceutically acceptable excipient.

263. A method of treating a subject suffering from a disease or condition, comprising administering to the subject in need the conjugate as described in any one of claims 259 to 261 or the pharmaceutical composition as described in claim 262.

264. A method of treating a subject suffering from cancer, comprising administering to the subject in need the conjugate as described in any one of claims 259 to 261 or the pharmaceutical composition as described in claim 262.

265. A method of treating a subject suffering from a tumor, comprising administering to the subject in need the conjugate as described in any one of claims 259 to 261 or the pharmaceutical composition as described in claim 262.

266. The method of claim 265, wherein the tumor is associated with cancer.

267. Use of the conjugate for treating a person suffering from a disease or condition, including administering to the person in need the conjugate as described in any one of claims 259 to 261 or the pharmaceutical composition as described in claim 262.

268. The use as claimed in claim 226, wherein the disease or condition is cancer.

269. The method of claim 264, 266, or 268, wherein the cancer is selected from: cancers of the head and neck, including tumors of the head, neck, nasal cavity, sinuses, nasopharynx, oral cavity, oropharynx, larynx, hypopharynx, salivary glands, and paragangliomas; cancers of the liver and biliary system, particularly hepatocellular carcinoma; intestinal cancer, particularly colorectal cancer; ovarian cancer; small cell lung cancer and non-small cell lung cancer (SCLC and NSCLC); breast cancer sarcomas, such as fibrosarcoma, malignant fibrous histiocytoma, embryonal rhabdomyosarcoma, leiomyosarcoma, neurofibrosarcoma, osteosarcoma, etc. Membrane sarcoma, liposarcoma, and alveolar soft tissue sarcoma; leukemias such as acute promyelocytic leukemia (APL), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML); vegetations of the central nervous system, especially brain cancer; multiple myeloma (MM); lymphomas such as Hodgkin's lymphoma, lymphoplasmacytic lymphoma, follicular lymphoma, mucosa-associated lymphoid tissue lymphoma, mantle cell lymphoma, B-cell large cell lymphoma, Burkitt lymphoma, and T-cell anaplastic large cell lymphoma.

270. The method of claim 264, 266 or 268, wherein the cancer is selected from cellular lymphoma, non-small cell lung cancer, large cell lung cancer, breast cancer and small cell lung cancer.

271. The method of claim 264, 266 or 268, wherein the cancer is a cellular lymphoma.

272. The method of claim 264, 266 or 268, wherein the cancer is non-small cell lung cancer.

273. The method of claim 264, 266 or 268, wherein the cancer is large cell lung cancer.

274. The method of claim 264, 266 or 268, wherein the cancer is breast cancer.

275. The method of claim 264, 266 or 268, wherein the cancer is small cell lung cancer.

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