Conjugates and uses thereof

Abstract

Provided herein is a Drug-Linker of Formula (X): (Formula (X)), or a pharmaceutically acceptable salt thereof, wherein the variables of Formula (X) are as defined in the application. Such compounds can be useful as anti-cancer agents.

Description

CONJUGATES AND USES THEREOF CROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 703,105 filed on October 3, 2024, and U.S. Provisional Patent Application No. 63 / 788,584 filed on April 14, 2025, the entire contents of each of which are incorporated herein by reference. BACKGROUND

[0002] Currently, small cytotoxic molecules for antibody drug conjugates can include camptothecin derivatives, which have antitumor effects by inhibiting topoisomerase I. Camptothecin derivatives can be used in antibody drug conjugates (ADC). However, there is still a need for further development of camptothecin derivatives and ADC drugs with better efficacy and / or safety. SUMMARY OF THE INVENTION

[0003] In an aspect, the present disclosure provides a Drug-Linker of Formula (X):Formula (X), or a pharmaceutically acceptable salt thereof, wherein; R40 is selectedD is selected from a Drug unit; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, S1, S2, S3, and S4are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl;K1is selected from KBand KL; KBis selected from: (i) a peptide unit, (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; KLis selected from: (i) a peptide unit, (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12-membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12 membered heterocycleFormula (X-I), or a pharmaceutically acceptable salt thereof, wherein; D is selected from a Drug unit; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent;S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, S1, S2, S3, and S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl;K1is selected from KBand KL; KBis selected from: (i) a peptide unit, (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; KLis selected from: (i) a peptide unit(iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle.

[0005] In an aspect, the present disclosure provides a Drug-Linker of Formula (X-II):Formula (X-II), or a pharmaceutically acceptable salt thereof, wherein; D is selected from a Drug unit; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3-C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, S1, S2, S3, and S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl,M1is a group which can react with a ligand to form a connector unit; K1is selected from KBand KL; KBis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; KLis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle.

[0006] In an aspect, the present disclosure provides a conjugate of the Formula (XX):Formula (XX), or a pharmaceutically acceptable salt thereof, wherein; R40 is selectedD is selected from a Drug unit; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene;S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M2, K1, S1, S2, S3, and S4are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl; L is a Targeting Unit; M2is a connector unit; K1is selected from KBand KL; KBis selected from: (i) a peptide unit, (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; KLis selected from:(ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle.

[0007] In some embodiments, Formula (XX) is represented byFormula (XX), or a pharmaceutically acceptable salt thereof, wherein DAR is an integer selected from about 0 to about 16.

[0008] In an aspect, the present disclosure provides a conjugate of the Formula (XX-I):F l (XX I)or a pharmaceutically acceptable salt thereof, wherein; D is selected from a Drug unit; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M2, K1, S1, S2, S3, and S4, are independently selected at each occurrence from:(i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl; L is a Targeting Unit; M2is a connector unit; K1is selected from KBand KL; KBis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; KLis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN;each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle.

[0009] In some embodiments, Formula (XX-I) is represented byor a pharmaceutically acceptable salt thereof .

[0010] In an aspect, the present disclosure provides a conjugate of the Formula (XX-II):Formula (XX-II), or a pharmaceutically acceptable salt thereof, wherein; D is selected from a Drug unit; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M2, K1, S1, S2, S3, and S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionallyN(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl; L is a Targeting Unit; M2is a connector unit; K1is selected from KBand KL; KBis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; KLis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle.Formula (XX-II), or a pharmaceutically acceptable salt thereof, wherein DAR is an integer selected from about 0 to about 16.

[0012] In an aspect, the present disclosure provides a method of treating a subject with a disease or disorder comprising administering to a subject in need thereof a conjugate or salt of for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I- Aa), Formula (XX-I-Ab), Formula (XX-I-C), Formula (XX-II), or Formula (XX-II-A), or a pharmaceutical composition of any one thereof. INCORPORATION BY REFERENCE

[0013] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will beobtained by reference to the following detailed description that sets forth illustrativeembodiments, in which the principles of the invention are utilized, and the accompanying drawings (also “figure” and “FIG.” herein), of which:

[0015] FIG.1 illustrates retention times of various drug linkers;

[0016] FIG.2 illustrates the LogP of various drug linkers;

[0017] FIG.3 illustrates the MFI value of various ADCs in MDA-MB-468 cells; and

[0018] FIG.4 illustrates the percentage bound of various ADCs in MDA-MB-468 cells;

[0019] FIG.5 illustrates the MFI value of various ADCs in H520 cells;

[0021] FIG.7 illustrates the internalization of various ADCs in H520 cells;

[0022] FIG.8 illustrates the percentage of proliferation inhibition of various ADCs in MDA-MB-468 cells

[0023] FIG.9 illustrates the percentage of proliferation inhibition of various ADCs in H520 cells;

[0024] FIG.10 illustrates the release of the payload from the drug-linker; and

[0025] FIG. 11 illustrates in vivo antitumor activity of different ADCs in H520 cells.DETAILED DESCRIPTION OF THE INVENTION

[0026] The following description sets forth numerous exemplary configurations, methods, parameters, and the like. It should be recognized, however, that such description is not intendedas a limitation on the scope of the present disclosure, but is instead provided as a desc ription ofexemplary embodiments.

[0027] In the following description, certain specific details are set forth in order to provide a thorough understanding of various embodiments of the disclosure. However, one skilled in the art will understand that the disclosure may be practiced without these details. Definitions

[0028] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this invention belongs. All patents and publications referred to herein are incorporated by reference.

[0029] "Alkyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, and preferably having from one to fifteen carbon atoms (i.e., C1-C15alkyl). In certain embodiments, an alkyl comprises one to thirteen carbon atoms (i.e., C1-C13alkyl). In certain embodiments, an alkyl comprises one to eight carbon atoms (i.e., C1-C8alkyl). In other embodiments, an alkyl comprises one to five carbon atoms (i.e., C1-C5alkyl). In other embodiments, an alkyl comprises one to four carbon atoms (i.e., C1-C4alkyl). In other embodiments, an alkyl comprises one to three carbon atoms (i.e., C1-C3alkyl). In other embodiments, an alkyl comprises one to two carbon atoms (i.e., C1- C2alkyl). In other embodiments, an alkyl comprises one carbon atom (i.e., C1alkyl). In other embodiments, an alkyl comprises five to fifteen carbon atoms (i.e., C5-C15alkyl). In other embodiments, an alkyl comprises five to eight carbon atoms (i.e., C5-C8alkyl). In other embodiments, an alkyl comprises two to five carbon atoms (i.e., C2-C5alkyl). In other embodiments, an alkyl comprises three to five carbon atoms (i.e., C3-C5alkyl). In certain embodiments, the alkyl group is selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl1,1-dimethylethyl (tert-butyl), 1-pentyl (n-pentyl). The alkyl is attached to the rest of the molecule by a single bond.

[0030] The terms “Cx-y” and “Cx-Cy” when used in conjunction with a chemical moiety, such as alkyl, alkenyl, or alkynyl is meant to include groups that contain from x to y carbons in the chain. For example, the terms “C1-6alkyl” or “C1-C6alkyl” refers to substituted or unsubstituted saturated hydrocarbon groups, including straight-chain alkyl and branched-chain alkyl groups that contain from 1 to 6 carbons. The terms –Cx-yalkylene- or –Cx-Cyalkylene- refers to a substituted or unsubstituted alkylene chain with from x to y carbons in the alkylene chain. For example –C1-6alkylene- or –C1-C6alkylene- may be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, any one of which is optionally substituted.

[0031] "Alkoxy" refers to a radical bonded through an oxygen atom of the formula –O-alkyl, where alkyl is an alkyl chain as defined above.

[0032] "Alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and preferably having from two to twelve carbon atoms (i.e., C2-C12alkenyl). In certain embodiments, an alkenyl comprises two to eight carbon atoms (i.e., C2-C8alkenyl). In certain embodiments, an alkenyl comprises two to six carbon atoms (i.e., C2-C6alkenyl). In other embodiments, an alkenyl comprises two to four carbon atoms (i.e., C2-C4alkenyl). The alkenylis attached to the rest of the molecule by a single bond, for example, ethenyl ( i.e., vinyl),prop-1-enyl (i.e., allyl), but-1-enyl, pent-1-enyl, penta-1,4-dienyl, and the like.

[0033] "Alkynyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, and preferably having from two to twelve carbon atoms (i.e., C2-C12alkynyl). In certain embodiments, an alkynyl comprises two to eight carbon atoms (i.e., C2-C8alkynyl). In other embodiments, an alkynyl comprises two to six carbon atoms (i.e., C2-C6alkynyl). In other embodiments, an alkynyl comprises two to four carbon atoms (i.e., C2-C4alkynyl). The alkynyl is attached to the rest of the molecule by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like.

[0034] The terms “Cx-yalkenyl” and “Cx-yalkynyl” refer to substituted or unsubstituted unsaturated aliphatic groups analogous in length and possible substitution to the alkyls describedabove, but that contain at least one double or triple bond, respectively. The term –Cx-yalkenylene- refers to a substituted or unsubstituted alkenylene chain with from x to y carbons in the alkenylene chain. For example, –C2-6alkenylene- may be selected from ethenylene,substituted. An alkenylene chain may have one double bond or more than one double bond in the alkenylene chain. The term –Cx-yalkynylene- refers to a substituted or unsubstituted alkynylene chain with from x to y carbons in the alkenylene chain. For example, –C2-6alkenylene- may be selected from ethynylene, propynylene, butynylene, pentynylene, and hexynylene, any one of which is optionally substituted. An alkynylene chain may have onetriple bond or more than one triple bond in the alkynylene chain.

[0035] "Alkylene" or "alkylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon andhydrogen, containing no unsaturation, and preferably having from one to twelve carbon ato ms,for example, methylene, ethylene, propylene, n-butylene, and the like. The alkylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkylene chain to the rest of the molecule and to the radical group may be through any two carbons within the chain. In certain embodiments, an alkylene comprises one to ten carbon atoms (i.e., C1-C8alkylene). In certain embodiments, an alkylene comprises one to eight carbon atoms (i.e., C1-C8alkylene). In other embodiments, an alkylene comprises one to five carbon atoms (i.e., C1-C5alkylene). In other embodiments, an alkylene comprises one to four carbon atoms (i.e., C1-C4alkylene). In other embodiments, an alkylene comprises one to three carbon atoms (i.e., C1-C3alkylene). In other embodiments, an alkylene comprises one to two carbon atoms (i.e., C1-C2alkylene). In other embodiments, an alkylene comprises one carbon atom (i.e., C1alkylene). In other embodiments, an alkylene comprises five to eight carbon atoms (i.e., C5-C8alkylene). In other embodiments, an alkylene comprises two to five carbon atoms (i.e., C2-C5alkylene). In other embodiments, an alkylene comprises three to five carbon atoms (i.e., C3-C5alkylene).

[0036] "Alkenylene" or "alkenylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon double bond, and preferably having from two to twelve carbon atoms. The alkenylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkenylene chain to the rest of the molecule and to the radical group may be through any two carbons within the chain. In certain embodiments, an alkenylene comprises two to ten carbon atoms (i.e., C2-C10alkenylene). In certain embodiments, an alkenylene comprises two to eight carbon atoms (i.e., C2-C8alkenylene). In other embodiments, an alkenylene comprises two to five carbon atoms (i.e., C2-C5alkenylene). In other embodiments, an alkenylene comprises two to four carbon atoms (i.e., C2-C4alkenylene). In other embodiments, an alkenylene comprisescomprises two carbon atom (i.e., C2alkenylene). In other embodiments, an alkenylene comprises five to eight carbon atoms (i.e., C5-C8alkenylene). In other embodiments, an alkenylene comprises three to five carbon atoms (i.e., C3-C5alkenylene).

[0037] "Alkynylene" or "alkynylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon triple bond, and preferably having from two to twelve carbon atoms. The alkynylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkynylene chain to the rest of the molecule and to the radical group may be through any two carbons within the chain. In certain embodiments, an alkynylene comprises two to ten carbon atoms (i.e., C2-C10alkynylene). In certain embodiments, an alkynylene comprises two to eight carbon atoms (i.e., C2-C8alkynylene). In other embodiments, an alkynylene comprises two to five carbon atoms (i.e., C2-C5alkynylene). In other embodiments, an alkynylene comprises two to four carbon atoms (i.e., C2-C4alkynylene). In other embodiments, an alkynylene comprises two to three carbon atoms (i.e., C2-C3alkynylene). In other embodiments, an alkynylene comprises two carbon atom (i.e., C2alkynylene). In other embodiments, an alkynylene comprises five to eight carbon atoms (i.e., C5-C8alkynylene). In other embodiments, an alkynylene comprises three to five carbon atoms (i.e., C3-C5alkynylene).

[0038] "Aryl" refers to a radical derived from an aromatic monocyclic or aromatic multicyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. The aromatic monocyclic or aromatic multicyclic hydrocarbon ring system contains only hydrogen and carbon and from five to eighteen carbon atoms, where at least one of the rings in the ring system is aromatic, i.e., it contains a cyclic, delocalized (4n+2) ^–electron system in accordance with the Hückel theory. The ring system from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin and naphthalene.

[0039] "Aralkyl" refers to a radical of the formula -Rc-aryl where Rcis an alkylene chain as defined above, for example, methylene, ethylene, and the like.

[0040] "Aralkenyl" refers to a radical of the formula –Rd-aryl where Rdis an alkenylene chain as defined above.

[0041] "Aralkynyl" refers to a radical of the formula -Re-aryl, where Reis an alkynylene chain as defined above.

[0042] “Activated group” refers to a cyclic alkyne which is highly reactive due to ring strain towards azide group to form a triazole.

[0043] "Activated disulfide group” refers to a disulfide which is capable to react with a thiol to form a new disulfide bond.

[0044] “Carbocycle” refers to a saturated, unsaturated or aromatic rings in which each atom of the ring is carbon. Carbocycle may include 3- to 10-membered monocyclic rings, 6- to 12- membered bicyclic rings, and 6- to 12-membered bridged rings. Each ring of a bicyclic carbocycle may be selected from saturated, unsaturated, and aromatic rings. An aromatic ring, e.g., phenyl, may be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated and aromatic bicyclic rings, as valence permits, are included in the definition of carbocyclic. Exemplary carbocycles includecyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. Bicycliccarbocycles may be fused, bridged or spiro-ring systems. In some cases, spiro-ring carbocycles have at least two molecular rings with only one common atom.

[0045] “Carbocyclene” refers to a divalent carbocycle linking the rest of the molecule to a radical group.

[0046] The term “unsaturated carbocycle” refers to carbocycles with at least one degree of unsaturation and excluding aromatic carbocycles. Examples of unsaturated carbocycles include cyclohexadiene, cyclohexene, and cyclopentene.

[0047] "Cycloalkyl" refers to a fully saturated monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, which includes fused or bridged ring systems, and preferably having from three to twelve carbon atoms. In certain embodiments, a cycloalkyl comprises three to ten carbon atoms. In other embodiments, a cycloalkyl comprises five to seven carbon atoms. The cycloalkyl may be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkyls include, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyl radicals include, for example, adamantyl, norbornyl (i.e., bicyclo[2.2.1]heptanyl), norbornenyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like.

[0048] "Cycloalkenyl" refers to an unsaturated non-aromatic monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, which includes fused or bridged ring systems, preferably having from three to twelve carbon atoms and comprising at least one double bond. In certain embodiments, a cycloalkenyl comprises three to ten carbon atoms. In other embodiments, a cycloalkenyl comprises five to seven carbon atoms. The cycloalkenyl may be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkenyls includes, e.g., cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl.

[0049] "Cycloalkylalkyl" refers to a radical of the formula –Rc-cycloalkyl where Rcis an alkylene chain as described above.

[0050] "Cycloalkylalkoxy" refers to a radical bonded through an oxygen atom of the formula –O-Rc-cycloalkyl where Rcis an alkylene chain as described above.

[0051] "Halo" or "halogen" refers to halogen substituents such as bromo, chloro, fluoro and iodo substituents.

[0052] As used herein, the term "haloalkyl" or “haloalkane” refers to an alkyl radical, as defined above, that is substituted by one or more halogen radicals, for example, trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, and the like. In some embodiments, the alkyl part of the fluoroalkyl radical is optionally further substituted. Examples of halogen substituted alkanes (“haloalkanes”) include halomethane (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), di-and trihalomethane (e.g., trichloromethane, 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 combinations of alkanes (or substituted alkanes) and halogens (e.g., Cl, Br, F, I, etc.). When an alkyl group is substituted with more than one halogen radicals, each halogen may be independently selected e.g., 1-chloro,2-fluoroethane.

[0053] "Fluoroalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more fluoro radicals, for example, trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, and the like.

[0054] "Aminoalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more amine radicals, for example, propan-2-amine, butane-1,2-diamine, pentane-1,2,4-triamine and the like.

[0055] "Hydroxyalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more hydroxy radicals, for example, propan-1-ol, butane-1,4-diol, pentane-1,2,4-triol, and the like.

[0056] "Alkoxyalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more alkoxy radicals, for example, methoxymethane, 1,3-dimethoxybutane, 1- methoxypropane, 2-ethoxypentane, and the like.

[0057] "Cyanoalkyl" as used herein refers to an alkyl radical, as defined above, that is substituted by one or more cyano radicals, for example, acetonitrile, 2-ethyl-3- methylsuccinonitrile, butyronitrile, and the like.

[0058] “Heterocycle” refers to a saturated or unsaturated or aromatic ring comprising one orinclude 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12- membered bridged rings. Each ring of a bicyclic heterocycle may be selected from saturated, unsaturated, and aromatic rings. Bicyclic heterocycles may be fused, bridged or spiro-ring systems. In some cases, spiro-ring heterocycles have at least two molecular rings with only one common atom. The spiro-ring heterocycle includes at least one heteroatom.

[0059] “Heterocyclene” refers to a divalent heterocycle linking the rest of the molecule to a radical group.

[0060] "Heteroaryl" or “aromatic heterocycle” refers to a radical derived from a heteroaromatic ring radical that comprises one to eleven carbon atoms and at least one heteroatom wherein each heteroatom may be selected from N, O, and S. As used herein, the heteroaryl ring may be selected from monocyclic or bicyclic and fused or bridged ring systems rings wherein at least one of the rings in the ring system is aromatic, i.e., it contains a cyclic, delocalized (4n+2) ^–electron system in accordance with the Hückel theory. The heteroatom(s) in the heteroaryl radical may be optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heteroaryl may be attached to the rest of the molecule through any atom of the heteroaryl, valence permitting, such as a carbon or nitrogen atom of the heteroaryl. Examples of heteroaryls include, but are not limited to, pyridine, pyrimidine, oxazole, furan, pyran, thiophene, isoxazole, benzimidazole, benzthiazole, and imidazopyridine.

[0061] An “X-membered heteroaryl” refers to the number of endocylic atoms, i.e., X, in the ring. For example, a 5-membered heteroaryl ring or 5-membered aromatic heterocycle has 5 endocyclic atoms, e.g., triazole, oxazole, thiophene, etc.

[0062] The term “unsaturated heterocycle” refers to heterocycles with at least one degree of unsaturation and excluding aromatic heterocycles. Examples of unsaturated heterocycles include dihydropyrrole, dihydrofuran, oxazoline, pyrazoline, and dihydropyridine. Heterocycles may be optionally substituted by one or more substituents such as those substituents described herein.

[0063] The term “substituted” refers to moieties having substituents replacing a hydrogen on one or more carbons or substitutable heteroatoms, e.g., NH, of the structure. It will be understood that “substitution” or “substituted with” includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, i.e., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. In certain embodiments, substituted refers to moieties having substituents replacing two hydrogen atoms on the same carbon atom, such as substituting the two hydrogen atoms on a single carbon with an oxo, imino or thioxo group.

[0064] As used herein, the term “substituted” is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents includeacyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this disclosure, the heteroatoms such as nitrogen may have hydrogen substituents and / or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms. In some embodiments, substituents may include any substituents described herein, for example: halogen, hydroxy, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N- H), oximo (=N-OH), hydrazino (=N- NH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, - Rb-C(O)ORa, -Rb-C(O)N(Ra)2, -Rb-O-Rc-C(O)N(Ra)2, -Rb-N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb-N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2), and -Rb-S(O)tN(Ra)2(where t is 1 or 2); and alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, and heterocycle, any of which may be optionally substituted by alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo (=N-OH), hydrazine (=N- NH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(O)N(Ra)2, -Rb-O-Rc-C(O)N(Ra)2, -Rb-N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb- N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2) and -Rb-S(O)tN(Ra)2(where t is 1 or 2); wherein each Rais independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, wherein each Ra, valence permitting, may be optionally substituted with alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo (=N-OH), hydrazine (=N- NH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(O)N(Ra)2, -Rb-O-Rc-C(O)N(Ra)2, -Rb-N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb- N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2) and -Rb-S(O)tN(Ra)2(where t is 1 or 2); and wherein each Rbis independently selected from adirect bond or a straight or branched alkylene, alkenylene, or alkynylene chain, and each R c is astraight or branched alkylene, alkenylene or alkynylene chain.

[0065] As used in the specification and claims, the singular form “a”, “an” and “the”includes plural references unless the context clearly dictates otherwise.

[0066] The term “salt” or “pharmaceutically acceptable salt” refers to salts derived from a variety of organic and inorganic counter ions well known in the art. Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. 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, p-toluenesulfonic acid, salicylic acid, and the like. Pharmaceutically acceptable base addition salts can be formed with 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, and the like. 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, and the like, specifically such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. In some embodiments, the pharmaceutically acceptable base addition salt is chosen from ammonium, potassium, sodium, calcium, and magnesium salts.

[0067] The phrases “parenteral administration” and “administered parenterally” as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion.

[0068] The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0069] The phrase “pharmaceutically acceptable excipient” or “pharmaceutically acceptablecarrier” as used herein means a pharmaceutically acceptable material, composition or vehicle,such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material. Each carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of materials which can serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose;sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen- free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) phosphate buffer solutions; and (21) other non-toxic compatible substances employed in pharmaceutical formulations.

[0070] In certain embodiments, the term “prevent” or “preventing” as related to a disease or disorder may refer to a compound that, in a statistical sample, reduces the occurrence of the disorder or condition in the treated sample relative to an untreated control sample, or delays the onset or reduces the severity of one or more symptoms of the disorder or condition relative to the untreated control sample.

[0071] The terms “treat,” “treating” or “treatment,” as used herein, may include alleviating, abating or ameliorating a disease or condition symptoms, preventing additional symptoms, ameliorating or preventing the underlying causes of symptoms, inhibiting the disease or condition, e.g., arresting the development of the disease or condition, relieving the disease or condition, causing regression of the disease or condition, relieving a condition caused by the disease or condition, or stopping the symptoms of the disease or condition either prophylactically and / or therapeutically.

[0072] The term "ligand" generally refers to a macromolecular compound capable of recognizing and binding to an antigen or receptor associated with a target cell. The ligand can beused to bring the drug to the target cell population that binds to the ligand, inc luding but notlimited to protein hormones, lectins, growth factors, antibodies, or others that can bind to cells, receptors and / or antigens molecule. The ligand can be an antibody. The ligand can be an antigen binding fragment.

[0073] 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 a target molecule. A Targeting Unit may include, for example, an antibody, a peptide, a ligand, a receptor, or a binding portion thereof. The target biological molecule maybe a biological receptor or other structure of a cell such as a tumor antigen.

[0074] The term “antibody” means whole antibodies and any antigen binding fragment (i.e., “antigen-binding portion”) or single chain variants thereof. A whole antibody is a proteinbonds. Each heavy chain comprises a heavy chain variable region (VH) and a heavy chain constant region comprising three domains, CH1, CH2 and CH3. Each light chain comprises a light chain variable region (VL or Vk) and a light chain constant region comprising one single domain, CL. The VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDRs), interspersed with more conserved framework regions (FRs). Each VH and VL comprises three CDRs and four FRs, arranged from amino- to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The variable regions contain a binding domain that interacts with an antigen. The constant regions may mediate the binding of the antibody to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (Clq) of the classical complement system.

[0075] The assignment of amino acid numbers, and of FR and CDR regions, in the heavy or light chain may be in accordance with IMGT®definitions (Lefranc et al., Dev Comp Immunol. (2003) 27(1):55-77); or the definitions of Kabat, Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, MD (1987 and 1991)); Chothia & Lesk, J Mol Biol. (1987) 196:901-17; Chothia et al., Nature (1989) 342:878-83; Abhinandan et al., Molecular Immunology (2008) 45(14):3832-39; MacCallum et al., J Mol Biol. (1996) 262:732- 45; or Honegger and Plückthun, J Mol Biol. (2001) 309(3):657-70. The CDR boundaries of various schemes are illustrated below, where the amino acid numbers are Kabat numbers unless otherwise indicated. CDR Delineations According to Various Schemes (Kabat Numbering)

[0076] An antibody is said to “specifically bind” to an antigen X if the antibody binds to antigen X with a KD of 1 x 10-7M or less, 5×10−8M or less, more preferably 1×10−8M or less,2×10−9M or less. The antibody can be chimeric, humanized, or, preferably, human. The heavy chain constant region can be engineered to affect glycosylation type or extent, to extend antibody half-life, to enhance or reduce inter-actions with effector cells or the complement system, or to modulate some other property. The engineering can be accomplished by replacement, addition, or deletion of one or more amino acids or by replacement of a domain with a domain from another immunoglobulin type, or a combination of the foregoing.

[0077] The term “antigen binding fragment” and “antigen binding portion” of an antibody (or simply “antibody portion” or “antibody fragment”) mean one or more fragments of an antibody that retain the ability to specifically bind to an antigen. It has been shown that the antigen-binding function of an antibody can be performed by fragments of a full-length antibody, such as (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CH1 domains; (ii) a F(ab’)2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fab’ fragment, which is essentially an Fab with part of the hinge region (see, for example, Abbas et al., Cellular and Molecular Immunology, 6th Ed., Saunders Elsevier 2007); (iv) a Fd fragment consisting of the VH and CH1 domains; (v) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody, (vi) a dAb fragment (Ward et al., (1989) Nature 341:544-546), which consists of a VH domain; (vii) an isolated complementarity determining region (CDR); and (viii) a nanobody, a heavy chain variable region 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 of the Fv fragment, VL and VH, are encoded by separate genes, they can be joined, using recombinant methods, by a synthetic linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules (known as single chain Fv, or scFv); see, e.g., 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 an antibody.

[0078] The term “isolated antibody” means an antibody that is substantially free of other antibodies having different antigenic specificities (e.g., an isolated antibody that specifically binds antigen X is substantially free of antibodies that specifically bind antigens other thanantigen X). An isolated antibody that specifically binds antigen X may, however, have cross -reactivity to other antigens, such as antigen X molecules from other species. In certainembodiments, an isolated antibody specifically binds to human antigen X and does not cross -react with other (non-human) antigen X antigens. Moreover, an isolated antibody may be substantially free of other cellular material and / or chemicals.

[0079] The term “monoclonal antibody” or “monoclonal antibody composition” means a preparation of antibody molecules of single molecular composition, which displays a single binding specificity and affinity for a particular epitope.

[0080] The term “human antibody” means an antibody having variable regions in which both the framework and CDR regions (and the constant region, if present) are derived from human germline immunoglobulin sequences. Human antibodies may include later 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-specific mutagenesis in vitro or by somatic mutation in vivo). However, “human antibody” does not include antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences.

[0081] The term “human monoclonal antibody” means an antibody displaying a binding specificity, which has variable regions in which both the framework and CDR regions are derived from human germline immunoglobulin sequences. In one embodiment, human monoclonal antibodies are produced by a hybridoma that includes a B cell obtained from a transgenic nonhuman animal, e.g., a transgenic mouse, having a genome comprising a humanheavy chain transgene and a light chain transgene fused to an immortalized cell.

[0082] The term "epitope" refers to the amino acids conventionally bound by an immunoglobulin VH / VL pair, such as the antibodies, antigen binding portions thereof and other binding agents described herein. Other binding agents comprise non-antibody scaffolds. An epitope can be formed on a polypeptide from contiguous amino acids or noncontiguous amino acids juxtaposed by tertiary folding of a protein. Epitopes formed from contiguous amino acids are typically retained on exposure to denaturing solvents, whereas epitopes formed by tertiary folding are typically lost on treatment with denaturing solvents. An epitope typically includes at least 3, and more usually, at least 5, about 9, or about 8-10 amino acids in a unique spatial conformation. An epitope defines the minimum binding site for an antibody, antigen binding portions thereof and other binding agent, and thus represents the target of specificity of an antibody, antigen binding portion thereof or other immunoglobulin-based binding agent. In the case of a single domain antibody, an epitope represents the unit of structure bound by a variable domain in isolation. An epitope may include non-amino acid components, such as glycan structures.

[0083] A “variant” antibody or antigen-binding portion has amino acid substitutions (which may be conservative or non-conservative) from a reference antibody or antigen-binding portion,binding portion. For example, the variant antibody or antigen-binding portion may retain at least 50%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% of the binding affinity of the reference antibody or antigen-binding portion, or may exceed the binding affinity of the reference antibody or antigen-binding portion.

[0084] The term “specifically binds” refers to the ability of a molecule (e.g., an antibody or antigen binding portion thereof or non-antibody scaffold) described herein to bind to a target with a KD of 10-5M (10000 nM) or less, e.g., 10-6M, 10-7M, 10-8M, 10-9M, 10-10M, 10-11M, 10-12M, or less. Specific binding can be influenced by, for example, the affinity and avidity of the antibody, antigen binding portion or other binding agent and the concentration of target polypeptide.

[0085] The term "about" when used in connection with percentages can mean + / -1%.

[0086] The term “cleavable unit” refers to a chemical group that may be cleaved by action of an internal or external, preferably external, stimulus. The stimulus triggering the cleavage of the cleavable unit may be for instance pH or temperature conditions, or the presence of an enzyme. Cleavage of the cleavable unit preferably triggers self-immolation of the phenyl-comprisinglinker of the compounds of the invention, and release of the active agent D.

[0087] The term “cleavable sugar unit” or “sugar cleavable unit” can refer to a sugar moiety, preferably a glucuronide or a galactoside.

[0088] The term “peptide cleavable unit” can refer to a polypeptide, preferably a dipeptide or a tripeptide. Linkers, Drug-Linkers and Conjugates of the Disclosure

[0089] In an aspect, the present disclosure provides a Drug-Linker of Formula (X):Formula (X), or a pharmaceutically acceptable salt thereof, wherein;D is selected from a Drug unit; X is selected from CH and N;T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, S1, S2, S3, and S4are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with oneC(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl; M1is a group which can react with a ligand to form a connector unit; K1is selected from KBand KL; KBis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; KLis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12-membered heterocycle.

[0090] In an aspect, the present disclosure provides a Drug-Linker of Formula (X-I):Formula (X-I), D is selected from a Drug unit; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene;S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, S1, S2, S3, and S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl; M1is a group which can react with a ligand to form a connector unit; K1is selected from KBand KL; KBis selected from: (i) a peptide unit, (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; KLis selected from: (i) a peptide unit,(iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle.

[0091] In an aspect, the present disclosure provides a Drug-Linker of Formula (X-II):Formula (X-II), D is selected from a Drug unit; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, ––S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, S1, S2, S3, and S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl;K1is selected from KBand KL; KBis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; KLis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle.

[0092] In some embodiments, Formula (X) or Formula (X-I) is represented by the structure of Formula (X-I-A)or a pharmaceutically acceptable salt thereof.

[0093] In some embodiments, Formula (X), Formula (X-I), or Formula (X-I-A) is represented by the structure of Formula (X-I-B)Formula (X-I-B), or a pharmaceutically acceptable salt thereof.

[0094] In some embodiments, Formula (X) or Formula (X-II) is represented by the structure of Formula (X-II-A)or a pharmaceutically acceptable salt thereof.

[0095] In some embodiments, Formula (X), Formula (X-II), or Formula (X-II-A) is represented by the structure of Formula (X-II-B)Formula (X-II-B), or a pharmaceutically acceptable salt thereof.

[0096] In some embodiments, Formula (X), Formula (X-I), or Formula (X-II) is represented by the structure of Formula (X III)Formula (X-III), or a pharmaceutically acceptable salt thereof.

[0097] In some embodiments, Formula (X), Formula (X-I), Formula (X-I-A), Formula (X- II), Formula (X-II-A), or Formula (X-III) is represented by the structure of Formula (X-III-A)Formula (X-III-A), or a pharmaceutically acceptable salt thereof.

[0098] In an aspect, the present disclosure provides a conjugate of the Formula (XX):Formula (XX), or a pharmaceutically acceptable salt thereof, wherein; R40 is selectedD is selected from a Drug unit; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O) C(O)N(R20) N(R20)S(O) S(O) N(R20) O C(O) OC(O)optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M2, K1, S1, S2, S3, and S4are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl; L is a Targeting Unit; M2is a connector unit; K1is selected from KBand KL; KBis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; KLis selected from: (i) a peptide unit, (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12-membered heterocycle.

[0099] In some embodiments, Formula (XX) is represented as, wherein DAR is an integer from about 1 to about 8.

[0100] In an aspect, the present disclosure provides a conjugate of the Formula (XX-I):Formula (XX-I), or a pharmaceutically acceptable salt thereof, wherein; D is selected from a Drug unit; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii)C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M2, K1, S1, S2, S3, and S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl; L is a Targeting Unit; M2is a connector unit; K1is selected from KBand KL; KBis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-memberedselected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; KLis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle.

[0101] In some embodiments, Formula (XX) is represented as, wherein DAR is an integer from about 1 to about 8.

[0102] In an aspect, the present disclosure provides a conjugate of the Formula (XX-II):Formula (XX-II), or a pharmaceutically acceptable salt thereof, wherein; D is selected from a Drug unit; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or moreN(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M2, K1, S1, S2, S3, and S4, are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl; L is a Targeting Unit; M2is a connector unit; K1is selected from KBand KL; KBis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; KLis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-memberedselected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle.

[0103] In some cases, Formula (XX-II) is represented asFormula (XX-II), wherein DAR is an integer from about 1 to about 8. In some cases, D is Exatecan.

[0104] In some embodiments, Formula (XX) or Formula (XX-I) is represented by the structure of Formula (XX-I-A)Formula (XX-I-A), or a pharmaceutically acceptable salt thereof.

[0105] In some embodiments, Formula (XX-I-A) is represented byFormula (XX-I-A), wherein DAR is an integer from about 1 to about 8.

[0106] In some embodiments, Formula (XX), Formula (XX-I), or Formula (XX-I-A) is represented by the structure of Formula (XX-I-B)Formula (XX-I-B), or a pharmaceutically acceptable salt thereof.

[0107] In some embodiments, Formula (XX-I-B) is represented byFormula (XX-I-B), wherein DAR is an integer from about 1 to about 8.

[0108] In some embodiments, Formula (XX) or Formula (XX-II) is represented by the structure of Formula (XX-II-A)Formula (XX-II-A), or a pharmaceutically acceptable salt thereof.

[0109] In some embodiments, Formula (XX-II-A) is represented byFormula (XX-II-A), wherein DAR is an integer from about 1 to about 8.

[0110] In some embodiments, Formula (XX), Formula (XX-II), or Formula (XX-II-A) is represented by the structure of Formula (XX-II-B)Formula (XX-II-B), or a pharmaceutically acceptable salt thereof.

[0111] In some embodiments, Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-II), or Formula (XX-II-A) is represented by the structure of Formula (XX-III)Formula (XX-III), or a pharmaceutically acceptable salt thereof.

[0112] In some embodiments, Formula (XX-III) is represented byFormula (XX-III), wherein DAR is an integer from about 1 to about 8.

[0113] In some embodiments, Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-II), Formula (XX-II-A), or Formula (XX-III) is represented by the structure of Formula (XX-III-A)Formula (XX-III-A), or a pharmaceutically acceptable salt thereof.

[0114] In some embodiments, Formula (XX-III-A) is represented byFormula (XX-III-A), wherein DAR is an integer from about 1 to about 8.

[0115] In some embodiments, Formula (XX-I-A) is represented bby the structure of Formula (XX-I-C)Formula (XX-I-C), or a pharmaceutically acceptable salt thereof.

[0116] In some embodiments, for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-II), or Formula (X-II-A), X is CH;S2 is selected fromS3is absent;each of which is optionally substituted with one or more substituents independently selected from C1-C6alkyl, -N(R30)C(O)R30, and -NHC(O)R30; K1is selected from KBand KL; KBis selected from a peptide unit, an oligosaccharide, -OS(O)2(OR30)2, and -OP(O)(OR30)2; and C4-10carbocycle which is optionally substituted with one or more substituents independently selected from -S(O)2R30, -OS(O)2OR30, -P(O)(OR30)2,-OP(O)(OR30)2, -NO2, and -CN; KLis selected from a peptide unit, an oligosaccharide, -OS(O)2(OR30)2, and -OP(O)(OR30)2; and C4-10carbocycle which is optionally substituted with one or more substituents independently selected from -S(O)2R30, -OS(O)2OR30, -P(O)(OR30)2,-OP(O)(OR30)2, -NO2, and -CN;S4 is absent or selected fromD is selected from

[0117] In some embodiments, for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-II), or Formula (X-II-A), X is CH: S1is selected fromS2 is selected fromS3is absent;Y-S4-K1is selected from ,.

[0118] In some embodiments, for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-II), or Formula (X-II-A), X is CH:,,.

[0119] In some embodiments, for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-II), or Formula (X-II-A),S3is absent;,

[0120] In some embodiments, for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-II), or Formula (X-II-A), X is CH;S3is absent;,.

[0121] In some embodiments, for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-II), or Formula (X-II-A), X is N;S3is absent;Y-S4-K1 is selected fromeach of which is optionally substituted with one or more substituents independently selected from C1-C6alkyl, -N(R30)C(O)R30, and -NHC(O)R30; K1is selected from KBand KL; KBis selected from a peptide unit, an oligosaccharide, -OS(O)2(OR30)2, and -OP(O)(OR30)2; and C4-10carbocycle which is optionally substituted with one or more substituents independently selected from -S(O)2R30, -OS(O)2OR30, -P(O)(OR30)2,-OP(O)(OR30)2, -NO2, and -CN; KLis selected from a peptide unit, an oligosaccharide, -OS(O)2(OR30)2, and -OP(O)(OR30)2; and C4-10carbocycle which is optionally substituted with one or more substituents independently selected from -S(O)2R30, -OS(O)2OR30, -P(O)(OR30)2,-OP(O)(OR30)2, -NO2, and -CN;S4 is absent or selected from.

[0122] In some embodiments, for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-II), or Formula (X-II-A), X i N,

[0123] In some embodiments, for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-II), or Formula (X-II-A),Ċ,.

[0124] In some embodiments, for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-II), or Formula (X-II-A),KBis selected from,, , ,.

[0125] In some embodiments, for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-II), or Formula (X-II-A), X is CH;each of which is optionally substituted with one or more substituents independently selected from C1-C6alkyl, -N(R30)C(O)R30, and -NHC(O)R30; K1is selected from KBand KL; KBis selected from a peptide unit, an oligosaccharide, -OS(O)2(OR30)2, and -OP(O)(OR30)2; and C4-10carbocycle which is optionally substituted with one or more substituents independently selected from -S(O)2R30, -OS(O)2OR30, -P(O)(OR30)2,-OP(O)(OR30)2, -NO2, and -CN; KLis selected from a peptide unit, an oligosaccharide, -OS(O)2(OR30)2, and -OP(O)(OR30)2; and C4-10carbocycle which is optionally substituted with one or more substituents independentlyS4 is absent or selected from.

[0126] In some embodiments, for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-II), or Formula (X-II-A), X is CH;

[0127] In some embodiments, for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-II), or Formula (X-II-A), X is CH;,, , ,

[0128] In some embodiments, for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-II), or Formula (X-II-A), X is CH;S3is absent;KBis selected fromĊ,or KLis selected from

[0129] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I),Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from selected from KBand KL. In some cases, K1is selected from KB. In some cases, KBis a hydrophilic spacer. In some cases, KBis selected from polyethylene glycol units, cyclodextrin units, polyamides, hydrophilic peptides, polysaccharides and dendrimers. In some cases, KBis selected from polyamides, hydrophilic peptides, and polysaccharides. In some cases, KBis selected from hydrophilic peptides and polysaccharides. In some cases, KBis selected from hydrophilic peptides. In some cases, KBis selected from polysaccharides.

[0130] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from selected from KBand KL. In some cases, K1is selected from KL. In some cases, KBis a hydrophilic spacer. In some cases, KLis selected from polyethylene glycol units, cyclodextrin units, polyamides, hydrophilic peptides, polysaccharides and dendrimers. In some cases, KLis selected from polyamides, hydrophilic peptides, and polysaccharides. In some cases, KLis selected from hydrophilic peptides and polysaccharides. In some cases, KLis selected from hydrophilic peptides. In some cases, KLis selected from polysaccharides.

[0131] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB),Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from KBand KL. In some cases, K1is selected from KB. In some cases, KBis selected a peptide unit, an oligosaccharide, -OS(O)2(OR30)2, and -OP(O)(OR30)2; and C4-10carbocycle which is optionally substituted with one or more substituents independently selected from halogen, - OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, - S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN. In some cases, KBis selected from a peptide unit, an oligosaccharide, -OS(O)2(OR30)2, and - OP(O)(OR30)2; and phenyl which is optionally substituted with one or more substituents independently selected from -S(O)2R30, -OS(O)2OR30, -P(O)(OR30)2,-OP(O)(OR30)2, -NO2, and -CN. In some cases, KBis selected from a peptide unit, an oligosaccharide, -OS(O)2(OR30)2, and -OP(O)(OR30)2; and phenyl which is optionally substituted with one or more substituents independently selected from -OS(O)2OR30and -OP(O)(OR30)2. In some cases, KBis selectedfrom a peptide unit,selected from a peptide unit,, , . In some cases,the peptide unit is a residue.

[0132] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from KBand KL. In some cases, K1is selected from KL. In some cases, KLis selected a peptide unit, an oligosaccharide OS(O) (OR30) and OP(O)(OR30) ; and C carbocycle which isOR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, - S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN. In some cases, KLis selected from a peptide unit, an oligosaccharide, -OS(O)2(OR30)2, and - OP(O)(OR30)2; and phenyl which is optionally substituted with one or more substituents independently selected from -S(O)2R30, -OS(O)2OR30, -P(O)(OR30)2,-OP(O)(OR30)2, -NO2, and -CN. In some cases, KLis selected from a peptide unit, an oligosaccharide, -OS(O)2(OR30)2, and -OP(O)(OR30)2; and phenyl which is optionally substituted with one or more substituents independently selected from -OS(O)2OR30and -OP(O)(OR30)2. In some cases, KLis selectedfrom a peptide unit,, , . In some cases, the peptideunit is a residue.

[0133] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from KBand KL. In some cases, K1is selected from KB. In some cases, the peptide unit of KBhas 1 to 50 amino acids. In some cases, the peptide unit of KBhas 1 to 20 amino acids. In some cases, the peptide unit of KBhas 1 to 10 amino acids. In some cases, the peptide unit of KBhas 2 to 50 amino acids. In some cases, the peptide unit of KBhas 2 to 40 amino acids. In some cases, the peptide unit of KBhas 2 to 30 amino acids. In some cases, the peptide unit of KBhas 2 to 20 amino acids. In some cases, the peptide unit of KBhas 2 to 10 amino acids. In some cases, the peptide unit of KBhas 5 to 10 amino acids. In some cases, the peptide unit of KBhas at least 1 amino acid. In some cases, the peptide unit of KBhas 1 amino acid. In some cases, the peptide unit of KBhas at least 2 amino acids. In some cases, the peptide unit of KBhas at least 5 amino acids. In some cases, the peptide unit of KBhas at least 8 amino acids. In some cases, the peptide unit of KBhas at least 10 amino acids. In some cases, the peptide unit of KBhas at most 10 amino acids. In some cases, the peptide unit of KBhas 10 amino acids. In some cases, the12 amino acids. In some cases, the peptide unit of KBhas at least 20 amino acids. In some cases, the peptide unit of KBhas at most 20 amino acids. In some cases, the peptide unit of KBhas 20 amino acids. In some cases, the peptide unit of KBhas at most 30 amino acids. In some cases, the peptide unit of KBhas at least 30 amino acids. In some cases, the amino acids of KBare selected from a group consisting of 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, the amino acids of KBare selected from a group consisting of 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, the amino acids of KBare selected from a group consisting of 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, the amino acidsof KB are selected from a group consisting of glycine, sarcosine, pro line, serine, alanine, and β-Alanine. In some cases, the amino acids of KBare selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of KBare selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, KBincludes at least one glycine. In some cases, KBincludes at least one proline. In some cases, KBincludes at least one serine. In some cases, KBincludes at least one alanine. In some cases, KBincludes at least one β-Alanine. In some cases, KBis a polysarcosine. In some cases, KBis a polysarcosine with ten repeating sarcosine units.

[0134] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from KBand KL. In some cases, K1is selected from KL. In some cases, the peptide unit of KLhas 1 to 50 amino acids. In some cases, the peptide unit of KLhas 1 to 20 amino acids. In some cases, theamino acids. In some cases, the peptide unit of KLhas 2 to 40 amino acids. In some cases, the peptide unit of KLhas 2 to 30 amino acids. In some cases, the peptide unit of KLhas 2 to 20 amino acids. In some cases, the peptide unit of KLhas 2 to 10 amino acids. In some cases, the peptide unit of KLhas 5 to 10 amino acids. In some cases, the peptide unit of KLhas at least 1 amino acid. In some cases, the peptide unit of KLhas 1 amino acid. In some cases, the peptide unit of KLhas at least 2 amino acids. In some cases, the peptide unit of KLhas at least 5 amino acids. In some cases, the peptide unit of KLhas at least 8 amino acids. In some cases, the peptide unit of KLhas at least 10 amino acids. In some cases, the peptide unit of KLhas at most 10 amino acids. In some cases, the peptide unit of KLhas 10 amino acids. In some cases, the peptide unit of KLhas at least 12 amino acids. In some cases, the peptide unit of KLhas at most 12 amino acids. In some cases, the peptide unit of KLhas at least 20 amino acids. In some cases, the peptide unit of KLhas at most 20 amino acids. In some cases, the peptide unit of KLhas 20 amino acids. In some cases, the peptide unit of KLhas at most 30 amino acids. In some cases, the peptide unit of KLhas at least 30 amino acids. In some cases, the amino acids of KLare selected from a group consisting of 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, the amino acids of KLare selected from a group consisting of 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, the amino acids of KLare selected from a group consisting of 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, the amino acids of KLare selected from a group consisting of glycine, sarcosine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of KLare selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of KLare selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, KLincludes at least one glycine. In some cases, KLincludes at least one proline. In some cases, KLincludes at least one serine. In some cases, KLincludes at least one alanine. In some cases, KLincludes at least one β-Alanine. In some cases, KLis a polysarcosine. In some cases, KLis a polysarcosine with ten repeating sarcosine units.

[0135] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for aFormula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from KBand KL. In some cases, K1is selected from KB. In some cases, KBis selected from a peptide unit, wherein the peptide unit has a terminal -NH2. In some cases, KBis selected from a peptide unit, wherein the peptide unit has a terminal -OH. In some cases, KBis selected from a peptide unit, wherein the peptide unit has a terminal. some cases, KBis selected froma peptide unit, wherein the peptide unit has a terminal .In some cases, KBis selected from a peptide, wherein the peptide has a terminal -NH2. In some cases, KBis selected from a peptide, wherein the peptide has a terminal -OH. In some cases, KBis selected from a peptide, wherein the peptide has a terminal. In some cases, KBis selected from a peptide,wherein the peptide has a terminal .

[0136] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from KBand KLIn some cases K1is selected from KLIn some cases KLis selected from a peptideunit, wherein the peptide unit has a terminal -OH. In some cases, KLis selected from a peptide unit, wherein the peptide unit has a terminalsome cases, KLis selected froma peptide unit, wherein the peptide unit has a terminal .In some cases, KLis selected from a peptide, wherein the peptide has a terminal -NH2. In some cases, KLis selected from a peptide, wherein the peptide has a terminal -OH. In some cases, KLis selected from a peptide, wherein the peptide has a terminal. In some cases, KLis selected from a peptide,wherein the peptide has a terminal .

[0137] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from KBand KL. In some cases, K1is selected from KB. In some cases, KBis selected from a peptide unit. In some cases, the peptide unit of KBhas 1 to 50 amino acids. In some cases, the peptide unit of KBhas 1 to 20 amino acids. In some cases, the peptide unit of KBhas 1 to 10 amino acids. In some cases, the peptide unit of KBhas 2 to 50 amino acids. In some cases, the peptide unit of KBhas 2 to 40 amino acids. In some cases, the peptide unit of KBhas 2 to 30 amino acids. In some cases, the peptide unit of KBhas 2 to 20 amino acids. In some cases, the peptide unit of KBhas 2 to 10 amino acids. In some cases, the peptide unit of KBhas 5 to 10 amino acids. In some cases, the peptide unit of KBhas at least 1 amino acids. In some cases, the peptide unit of KBhas 1 amino acid. In some cases, the peptide unit of KBhas at least 2 amino acids. In some cases the peptide unit of KBhas at least 5 amino acids In some cases the peptide unit ofIn some cases, the peptide unit of KBhas at most 10 amino acids. In some cases, the peptide unit of KBhas 10 amino acids. In some cases, the peptide unit of KBhas at least 12 amino acids. In some cases, the peptide unit of KBhas at most 12 amino acids. In some cases, the peptide unit of KBhas at least 20 amino acids. In some cases, the peptide unit of KBhas at most 20 amino acids. In some cases, the peptide unit of KBhas 20 amino acids. In some cases, the peptide unit of KBhas at most 30 amino acids. In some cases, the peptide unit of KBhas at least 30 amino acids. In some cases, KBis a peptide unit selected from a glycine and two adjacent sarcosines. In some cases KBis a peptide unit selected from a glycine and three adjacent sarcosines. In some cases, KBis a peptide unit selected from a glyicine and four adjacent sarcosines. In some cases, when a peptide unit includes adjacent sarcosines, there is at least one other amino acid present. In some cases, KBincludes a glycine and two adjacent sarcosines. In some cases, KBincludes a glycine and three adjacent sarcosines. In some cases, KBincludes a glycine and four adjacent sarcosines. In some cases, KBis a peptide unit selected from a glycine and two adjacent sarcosines. In some cases KBis a peptide unit selected from a glycine and three adjacent sarcosines. In some cases,KB is a peptide unit selected from a glyicine and four adjacent sarcosines. In some cases, K Bincludes 2 glycines and 8 sarcosines. In some cases, KBincludes 3 glycines and 8 sarcosines. In some cases, KBincludes 4 glycines and 7 sarcosines. In some cases, KBincludes 3 glycines and 7 sarcosines. In some cases, KBincludes 3 glycines and 6 sarcosines. In some cases, KBincludes 3 glycines and 5 sarcosines. In some cases, KBincludes 3 glycines and 4 sarcosines. In some cases, KBincludes 3 glycines and 3 sarcosines. In some cases, KBincludes 3 glycines and 9 sarcosines. In some cases, KBincludes 3 glycines and 10 sarcosines. In some cases, KBincludes 5 glycines and 5 sarcosines. In some cases, KBincludes 4 glycines and 4 sarcosines. In some cases, KBincludes 4 glycines and 5 sarcosines. In some cases, KBincludes 5 glycines and 4 sarcosines. In some cases, KBhas at most 9 sarcosines. In some cases, KBhas at most 8 sarcosines. In some cases, KBhas at most 7 sarcosines. In some cases, KBhas at most 6 sarcosines. In some cases, KBhas at most 5 sarcosines. In some cases, KBhas at most 4 sarcosines. In some cases, KBhas at most 3 sarcosines. In some cases, KBhas at most 2 sarcosines. In some cases, KBhas at most 1 sarcosine. In some cases, KBhas at most 9 glycines. In some cases, KBhas at most 8 glycines. In some cases, KBhas at most 7 glycines. In some cases, KBhas at most 6 glycines. In some cases, KBhas at most 5 glycines. In some cases, KBhas at most 4 glycines. In some cases, KBhas at most 3 glycines. In some cases, KBhas at most 2 glycines. In some cases, KBhas at most 1 glycine. In some cases, the amino acids of KBare selected from a group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine,β-Alanine. In some cases, the amino acids of KBare selected from a group consisting of 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, the amino acids of KBare selected from a group consisting of 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, the amino acidsof KB are selected from a group consisting of glycine, sarcosine, proline, serine, alanine, and β -Alanine. In some cases, the amino acids of KBis selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of KBare selected from a group consisting of proline, serine, alanine, and β-Alanine. In some cases, the amino acids of KBincludes at least one glycine and at least one other amino acid. In some cases, the amino acids ofKB includes at least one glycine and at least one sarcosine. In some cases, the amino acids of K Bincludes at least one glycine and at least one other amino acid selected from proline, serine, alanine, and β-Alanine. In some cases, the amino acids of KBare selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, KBincludes at least one glycine. In some cases, KBincludes at least one proline. In some cases, KBincludes at least one serine. In some cases, KBincludes at least one alanine. In some cases, KBincludes at least one β-Alanine.

[0138] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from KBand KL. In some cases, K1is selected from KL. In some cases, KLis selected from a peptide unit. In some cases, the peptide unit of KLhas 1 to 50 amino acids. In some cases, the peptide unit of KLhas 1 to 20 amino acids. In some cases, the peptide unit of KLhas 1 to 10 amino acids. In some cases, the peptide unit of KLhas 2 to 50 amino acids. In some cases, the peptide unit of KLhas 2 to 40 amino acids. In some cases, the peptide unit of KLhas 2 to 30 aminounit of KLhas 2 to 10 amino acids. In some cases, the peptide unit of KLhas 5 to 10 amino acids. In some cases, the peptide unit of KLhas at least 1 amino acids. In some cases, the peptide unit of KLhas 1 amino acid. In some cases, the peptide unit of KLhas at least 2 amino acids. In some cases, the peptide unit of KLhas at least 5 amino acids. In some cases, the peptide unit of KLhas at least 8 amino acids. In some cases, the peptide unit of KLhas at least 10 amino acids. In some cases, the peptide unit of KLhas at most 10 amino acids. In some cases, the peptide unit of KLhas 10 amino acids. In some cases, the peptide unit of KLhas at least 12 amino acids. In some cases, the peptide unit of KLhas at most 12 amino acids. In some cases, the peptide unit of KLhas at least 20 amino acids. In some cases, the peptide unit of KLhas at most 20 amino acids. In some cases, the peptide unit of KLhas 20 amino acids. In some cases, the peptide unit of KLhas at most 30 amino acids. In some cases, the peptide unit of KLhas at least 30 amino acids. In some cases, KLis a peptide unit selected from a glycine and two adjacent sarcosines. In some cases KLis a peptide unit selected from a glycine and three adjacent sarcosines. In some cases, KLis a peptide unit selected from a glyicine and four adjacent sarcosines. In some cases, when a peptide unit includes adjacent sarcosines, there is at least one other amino acid present. In some cases, KLincludes a glycine and two adjacent sarcosines. In some cases, KLincludes a glycine and three adjacent sarcosines. In some cases, KLincludes a glycine and four adjacent sarcosines. In some cases, KLis a peptide unit selected from a glycine and two adjacent sarcosines. In some cases KLis a peptide unit selected from a glycine and three adjacent sarcosines. In some cases,KL is a peptide unit selected from a glyicine and four adjacent sarcosines. In some cases, K Lincludes 2 glycines and 8 sarcosines. In some cases, KLincludes 3 glycines and 8 sarcosines. In some cases, KLincludes 4 glycines and 7 sarcosines. In some cases, KLincludes 3 glycines and 7 sarcosines. In some cases, KLincludes 3 glycines and 6 sarcosines. In some cases, KLincludes 3 glycines and 5 sarcosines. In some cases, KLincludes 3 glycines and 4 sarcosines. In some cases, KLincludes 3 glycines and 3 sarcosines. In some cases, KLincludes 3 glycines and 9 sarcosines. In some cases, KLincludes 3 glycines and 10 sarcosines. In some cases, KLincludes 5 glycines and 5 sarcosines. In some cases, KLincludes 4 glycines and 4 sarcosines. In some cases, KLincludes 4 glycines and 5 sarcosines. In some cases, KLincludes 5 glycines and 4 sarcosines. In some cases, KLhas at most 9 sarcosines. In some cases, KLhas at most 8 sarcosines. In some cases, KLhas at most 7 sarcosines. In some cases, KLhas at most 6 sarcosines. In some cases, KLhas at most 5 sarcosines. In some cases, KLhas at most 4 sarcosines. In some cases, KLhas at most 3 sarcosines. In some cases, KLhas at most 2 sarcosines. In some cases, KLhas at most 1 sarcosine. In some cases, KLhas at most 9 glycines. In some cases, KLhas at most 8 glycines. In some cases, KLhas at most 7 glycines. In somehas at most 4 glycines. In some cases, KLhas at most 3 glycines. In some cases, KLhas at most 2 glycines. In some cases, KLhas at most 1 glycine. In some cases, the amino acids of KLare selected from a group consisting of 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, the amino acids of KLare selected from a group consisting of 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, the amino acids of KLare selected from a group consisting of 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, the amino acidsof KL are selected from a group consisting of glycine, sarcosine, proline, serine, alanine, and β -Alanine. In some cases, the amino acids of KLis selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of KLare selected from a group consisting of proline, serine, alanine, and β-Alanine. In some cases, the amino acids of KLincludes at least one glycine and at least one other amino acid. In some cases, the amino acids of KLincludes at least one glycine and at least one sarcosine. In some cases, the amino acids of KLincludes at least one glycine and at least one other amino acid selected from proline, serine, alanine, and β-Alanine. In some cases, the amino acids of KLare selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, KLincludes at least one glycine. In some cases, KLincludes at least one proline. In some cases, KLincludes at least one serine. In some cases, KLincludes at least one alanine. In some cases, KLincludes at least one β-Alanine.

[0139] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected fromsome cases, PASylation is a peptide comprising proline, alanine, and serine. In some cases,PASylation is a peptide consisting of only proline, alanine, and serine. In some cases, K Bincludes PASylation of less than PAS100. For example, PAS100 refers to a peptide having 100 amino acids, wherein the amino acids are selected from proline, alanine, and serine. In some cases, KBincludes PASylation of less than PAS50. In some cases, KBincludes PASylation of less than PAS25. In some cases, KBincludes PASylation of more than PAS5. In some cases, KBincludes PASylation of more than PAS9. In some cases, KBincludes PASylation of more than PAS15. In some cases, KBincludes PASylation of PAS5 to PAS25. In some cases, KBincludes PASylation of PAS10 to PAS20. In some cases, KBincludes PASylation of PAS10. In some cases, KBincludes PASylation of PAS20. In some cases, KBincludes a beta-alanine that linksthe PASylation to the drug-linker. In some cases, PASylation is used to extend the plasma half -life. In some cases, PASylation is used to increase solubility. In some cases, PASylation is used to increase solubility without generating secondary structures. In some cases, PASylation isPASylation is s, y .

[0140] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-KBand KL. In some cases, K1is selected from KL. In some cases, KLincludes PASylation. In some cases, PASylation is a peptide comprising proline, alanine, and serine. In some cases,PASylation is a peptide consisting of only proline, alanine, and serine. In some cases, K Lincludes PASylation of less than PAS100. For example, PAS100 refers to a peptide having 100 amino acids, wherein the amino acids are selected from proline, alanine, and serine. In some cases, KLincludes PASylation of less than PAS50. In some cases, KLincludes PASylation of less than PAS25. In some cases, KLincludes PASylation of more than PAS5. In some cases, KLincludes PASylation of more than PAS9. In some cases, KLincludes PASylation of more than PAS15. In some cases, KLincludes PASylation of PAS5 to PAS25. In some cases, KLincludes PASylation of PAS10 to PAS20. In some cases, KLincludes PASylation of PAS10. In some cases, KLincludes PASylation of PAS20. In some cases, KLincludes a beta-alanine that linksthe PASylation to the drug-linker. In some cases, PASylation is used to extend the plasma half -life. In some cases, PASylation is used to increase solubility. In some cases, PASylation is usedto increase solubility without generating secondary structures. In some cases, PASyla tion is.

[0141] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from KBand KL. In some cases, K1is selected from KB. In some cases, KBis selected from an oligosaccharide. In some cases, the oligosaccharide will include a connector unit which attaches the oligosaccharide to the rest of the molecule. In some cases, the connector unit is beta alanine., w eren s seected rom to 0. n some cases, s selectedselected 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, KBis selected from. some cases, KBis selected from.

[0142] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from KBand KL. In some cases, K1is selected from KL. In some cases, KLis selected from an oligosaccharide. In some cases, the oligosaccharide will include a connector unit which attaches the oligosaccharide to the rest of the molecule. In some cases, the connector unit is beta alanine. In some cases, the connector unit is. In some cases, the connector unit is. ,, wherein k is selected from 2 to 10. In some cases, KLis selected2. 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.

[0143] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from KBand KL. In some cases, K1is selected from KB. In some cases, KBis selected from an oligosaccharide. In some cases, the oligosaccharide will include a connector unit which attaches the oligosaccharide to the rest of the molecule. In some cases, the connector unit is beta alanine. In some cases, the connector unit is. In some cases, the connector unit is, rom 2 to 10., wherein 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 somefrom

[0144] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from KBand KL. In some cases, K1is selected from KL. In some cases, KLis selected from an oligosaccharide. In some cases, the oligosaccharide will include a connector unit which attaches the oligosaccharide to the rest of the molecule. In some cases, the connector unit is beta alanine. In some cases, the connector unit is. In some cases, the connector unit is. ,, wherein k is selected from 2 to 10.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.

[0145] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB),Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from KBand KL. In some cases, K1is selected from KB. In some cases, KBis selected from -OS(O)2(OR30)2, and -OP(O)(OR30)2; and C4-10carbocycle which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN. In some cases, KBis selected from -OS(O)2(OR30)2, and -OP(O)(OR30)2; and C4-10carbocycle which is optionally substituted with one or more substituents independently selected from -S(O)2R30, - OS(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN. In some cases, KBis selected from -OS(O)2(OR30)2, and -OP(O)(OR30)2; and phenyl which is optionally substituted with one or more substituents independently selected from -S(O)2R30, - OS(O)2OR30, -P(O)(OR30)2,-OP(O)(OR30)2, -NO2, and -CN. In some cases, KBis selected from -OS(O)2(OR30)2, and -OP(O)(OR30)2; and C4-10carbocycle which is optionally substituted with one or more substituents independently selected from -OS(O)2OR30and -OP(O)(OR30)2. In some cases, KBis selected from -OS(O)2(OR30)2, and -OP(O)(OR30)2; and phenyl which is optionally substituted with one or more substituents independently selected from -OS(O)2OR30some cases, KB is selected from, , and.

[0146] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected fromfrom -OS(O)2(OR30)2, and -OP(O)(OR30)2; and C4-10carbocycle which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN. In some cases, KLis selected from -OS(O)2(OR30)2, and -OP(O)(OR30)2; and C4-10carbocycle which is optionally substituted with one or more substituents independently selected from -S(O)2R30, - OS(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN. In some cases, KLis selected from -OS(O)2(OR30)2, and -OP(O)(OR30)2; and phenyl which is optionally substituted with one or more substituents independently selected from -S(O)2R30, - OS(O)2OR30, -P(O)(OR30)2,-OP(O)(OR30)2, -NO2, and -CN. In some cases, KLis selected from -OS(O)2(OR30)2, and -OP(O)(OR30)2; and C4-10carbocycle which is optionally substituted with one or more substituents independently selected from -OS(O)2OR30and -OP(O)(OR30)2. In some cases, KLis selected from -OS(O)2(OR30)2, and -OP(O)(OR30)2; and phenyl which is optionally substituted with one or more substituents independently selected from -OS(O)2OR30and -OP(O)(OR30)2.

[0147] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from KBand KL. In some cases, K1is selected from KB. In some cases, KBis selected from. In some cases, KBis selected from. In some cases, KBis selected fromsome cases, KB is selected from. In some cases, KB is selected from. some cases, each n is selected from 5 to 12. In some cases, each n is selected from 5 to 10. In some cases, each n is selected from 7 to 12. In some cases, each n is selected from 8 to 10. In some cases, each n is 5. In some cases, each n is 6. In some cases, each n is 7. In some cases, each n is 8. In some cases, each n is 9. In some cases, n is 10. In some cases, each n is selected from 5 and 10. In some cases, each R5for each n is independently selected from hydrogen and methyl.

[0148] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected fromIn some cases, KLis selected from. some cases, each n is selected from 5 to 12. In some cases, each n is selected from 5 to 10. In some cases, each n is selected from 7 to 12. In some cases, each n is selected from 8 to 10. In some cases, each n is 5. In some cases, each n is 6. In some cases, each n is 7. In some cases, each n is 8. In some cases, each n is 9. In some cases, n is 10. In some cases, each n is selected from 5 and 10. In some cases, each R5for each n is independently selected from hydrogen and methyl. In some cases, KLis selected, ,. some cases, KLis selected from. some cases, KLis selected from

[0149] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from KBand KL. In some cases, K1is selected from KL. In some cases, KLis selected fromsome cases, KLis selected from. some cases, KLis selected from. , KLis selected from.

[0150] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from KBand KL. In some cases, K1is selected from KB. In some cases, the peptide unit of KBhas aterminus unit. In some cases, KB is selected from,,, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, j is selected from 1 to 20. In some cases, j is selected from 1 to 15. In some cases, j is selected from 5 to 10. In some cases, j is selected from 5 to 15. In some cases, j is selected fromsome 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, R6is selected from -OR7, -NHR7, and -NHC(O)R7, wherein R7is selected from hydrogen; C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycleand 3- to 10-membered heterocycle. In some cases, R6is selected from -OH, -NH2, , and. In some cases, R6is selected from -OH, -NH2, and. In some cases, R6is selected from -OH, and -NH2. In some cases, R6is -OH. In some cases, R6is -NH2.In some cases, R6is. In some cases, R6is .

[0151] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), K1is selected from KBand KL. In some cases, K1is selected from KB. In some cases, the peptide unit of KLhas a, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30., wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, j is selected from 1 to 20. In some cases, j is selected from 1 to 15. In some cases, j is selected from 5 to 10. In some cases,j is selected from 5 to 15. In some cases, j is selected from 5 to 20. In some cases, j is selectedfrom 10 to 20. In some cases, j is selected from 1 to 5. 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, each R 6 isindependently selected from C1-4alkyl, -OR7, -NHR7, and -NHC(O)R7, wherein each R7is selected from hydrogen; C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle. In some cases, each R6is independently selected fromindependently selected from methyl, -OH, -NH2, and . In some cases, each R6is independently selected from methyl, -OH, and -NH2. In some cases, each R6is -OH. In some cases, each R6is -NH2. In some cases, each R6is. In some cases, each R6is. In some cases, each R6is methyl.

[0152] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-selected from KBand KL. In some cases, K1is selected from KL. In some cases, the peptide unit of KLhas a terminus unit. In some cases, KLis selected from, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, each KLis independently selected fromterminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, each KLis independently selected from, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, j is selected from 1 to 20. In some cases, j is selected from 1 to 15. In some cases, j is selected from 5 to 10. In some cases, j is selected from 5 to 15. In some cases, j is selected from 5 to 20. In some cases, j is selected from 10 to 20. In some cases, j is selected from 1 to 5. 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, each R6is independently selected from C1-4alkyl, C1-4alkyl- C(O)NHR7, -OR7, -NHR7, and -NHC(O)R7, wherein each R7is selected from hydrogen; C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle. In some cases, each R6is independently selected from C1-4alkyl- C(O)NH2. In some cases, each R6is independently selected from C1alkyl-C(O)NH2. In some cases, each R6is independently selected from. In some cases, each R6is independently selected from C1-4alkyl, -OR7, -NHR7, and -NHC(O)R7, wherein each R7is selected from hydrogen; C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30,S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle. In some cases, each R6is independently selected from methyl, ethyl, -OH, -NH2,, . In some cases, each R6is independentlyselected from methyl, -OH, -NH2, and . In some cases, each R6is independently selected from methyl, -OH, and -NH2. In some cases, each R6is -OH. In some cases, each R6is -NH2. In some cases, each R6is. In some cases, each R6is . In some cases, each R6is methyl.

[0153] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), KBis selected from,,. In some cases, KB is selected from. In somecases, KBis selected from. In some cases, KBis selected from ,,. In some cases, KBis selected from. In some cases, KBis. In some cases, KBis. In some cases, KBcases, KBis,.. , . In some cases,. , .

[0154] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB),Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), KLis selected from,,. In some cases,some cases,In some cases, KLiss, .

[0155] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), KLis selected from. some cases, KLis selected from, KLis selected from. some cases, KLis selected from.

[0156] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-III), Formula (X-III-A), Formula (X-III-Aa), or Formula (X-III-Aaa), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-III), or Formula (XX-III-A), S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, –S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–. In some cases, S1is selected from: (i) an optionally substituted C6-C10alkylene wherein one or more alkylene units of the C6-C10alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, or –C(O)–. In some cases, S1is an optionally substituted C1alkylene. In some cases, S1is an optionally substituted C2alkylene. In some cases, S1is an optionally substituted C3alkylene. In some cases, S1is an optionally substituted C4alkylene. In some cases, S1is an optionally substituted C5alkylene. In some cases, S1is an optionally substituted C6alkylene. In some cases, S1is an optionally substituted C7alkylene. In some cases, S1is an optionally substituted C8alkylene. In someC10alkylene. In some cases, S1is an optionally substituted C11alkylene. In some cases, S1is an optionally substituted C12alkylene. In some cases, S1is an optionally substituted C13alkylene. In some cases, S1is an optionally substituted C14alkylene. In some cases, S1is an optionally substituted C15alkylene. In some cases, S1is an optionally substituted C16alkylene. In some cases, S1is an optionally substituted C17alkylene. In some cases, S1is an optionally substituted C18alkylene. In some cases, S1is an optionally substituted C19alkylene. In some cases, S1is an optionally substituted C20alkylene. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, – N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or – P(O)(R20)2–. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, or –C(O)–. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by –N(R20)–. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by –N(R20)C(O)–. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by –C(O)N(R20)–. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by –C(O)–. In some cases, the one or more alkylene units of the alkylene of S1are optionally and independently replaced by –O–. In some cases, if an alkylene unit of the alkylene is replaced, the alkylene may be referred to as a resulting alkylene. In some cases, if two or more of the alkylene units of S1are replaced, the replaced alkylene units are not adjacent alkylene units. In some cases, if two or more of the alkylene units of S1are replaced, the adjacent alkylene units of the resulting alkylene are not replaced. In some cases, if two or more of the alkylene units of S1are replaced, the resulting alkylene has no repeating heteroatoms of adjacent alkylene units. In some cases, if two or more of the alkylene units of S1are replaced, the resulting alkylene has no repeating of the same heteroatoms of adjacent alkylene units. In some cases, if two or more of the alkylene units of S1are replaced, the resulting alkylene unit has no -N-N- or -O-O-. In some cases, if two or more of the alkylene units of S1are replaced, the resulting alkylene unit is a stable alkylene. In some cases, if two or more of the alkylene units of S1are replaced, the resulting alkylene unit is an unreactive alkylene. In some cases, the resulting alkylene has only 1 heteroatom. In some cases, the resulting alkylene has only 2 heteroatoms, wherein the 2 heteroatoms are different from each other. In some cases, the resulting alkylene has only 2 heteroatoms, wherein the 2 heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only 3 heteroatoms, wherein the 3 heteroatoms are not adjacent to each other. In some cases, the alkylene has 0 replaced units. In some cases, the alkylene has 1replaced units. In some cases, the alkylene has 4 replaced units. In some cases, the alkylene has 5 replaced units. In some cases, the alkylene has 6 replaced units. In some cases, no adjacent alkylene units of the alkylene are replaced. In some cases, no adjacent alkylene units resulting in two or more adjacent heteroatoms are present in the resulting alkylene (e.g., adjacent – N(R20)S(O)2– and –N(R20)– are not allowed, but the singular –N(R20)S(O)2– is allowed). In some cases, two heteroatoms can be present in a resulting alkylene if they come from a singular replaced alkylene unit. In some cases, two heteroatoms can be present in a resulting alkylene if they come from a singular replaced alkylene unit. In some cases, a resulting alkylene has two heteroatoms, the two heteroatoms are from a singular replaced alkylene unit. In some cases, there are two heteroatoms in a resulting alkylene if they result from a singular replacement of an alkylene unit. In some cases, the optional substituents on S1are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle. In some cases, the optional substituents on S1are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN. In some cases, the optional substituents on S1are independently selected at each occurrence from: halogen, -OR30, - N(R30)2, =O, and -CN. In some cases, the optional substituents on S1are independently selected at each occurrence from: =O.

[0157] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-III), Formula (X-III-A), Formula (X-III-Aa), or Formula (X-III-Aaa), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-III), or Formula (XX-III-A), S1is a branched alkylene.

[0158] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I),Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-III), Formula (X-III-A), Formula (X-III-Aa), or Formula (X-III-Aaa), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-III), or Formula (XX-III-A), S1is selected from an optionally substituted C4-C10alkylene wherein one or more alkylene units of the C4-C10alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, or –C(O)–.

[0159] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-III), Formula (X-III-A), Formula (X-III-Aa), or Formula (X-III-Aaa), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-III), or Formula (XX-III-A), S1is selected from an optionally substituted C1-C3alkylene wherein one or more alkylene units of the C1-C3alkylene are optionally and independently replaced by –N(R20)–. In some cases, S1is selected from an optionally substituted C1-C2alkylene wherein one or more alkylene units of the C1-C2alkylene are optionally and independently replaced by –N(R20)–. In some cases, S1is selected from an optionally substituted C2-C3alkylene wherein one or more alkylene units of the C2-C3alkylene are optionally and independently replaced by –N(R20)–. In some cases, S1is selected from. In some cases, S1is.

[0160] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-III), Formula (X-III-A), Formula (X-III-Aa), or Formula (X-III-Aaa), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-III), or Formula (XX-III-A), S1is selected fromIn some cases S1is represented

[0161] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-III), Formula (X-III-A), Formula (X-III-Aa), or Formula (X-III-Aaa), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-III), or Formula (XX-III-A), S1is selected from. some cases, S1is selected from, some cases, S1is selected fromsome cases,. In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug- Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-III), Formula (X- III-A), Formula (X-III-Aa), or Formula (X-III-Aaa), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-II), Formula (XX-II-A),Formula (XX-II-B), Formula (XX-III), or Formula (XX-III-A), S1is represented by. In some cases, S1is represented by.

[0162] In some embodiments, for a Drug-Linker or salt of Formularepresentedisselected from. some cases,is selected from.

[0163] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-III), Formula (X-III-A), Formula (X-III-Aa), or Formula (X-III-Aaa), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-III), or Formula (XX-III-A), S2is selected from an optionally substituted C8-C12alkylene wherein one or more alkylene units of the C8-C12alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –O–, and –C(O)–. In some cases, S2is selected from an optionally substituted C1- C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–. In some cases, S2is selected from an optionally substituted C6-C10alkylene wherein one or more alkylene units of the C6-C10alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)– –C(O)N(R20)– or –C(O)– In some cases S2is an optionally substituted C1optionally substituted C3alkylene. In some cases, S2is an optionally substituted C4alkylene. In some cases, S2is an optionally substituted C5alkylene. In some cases, S2is an optionally substituted C6alkylene. In some cases, S2is an optionally substituted C7alkylene. In some cases, S2is an optionally substituted C8alkylene. In some cases, S2is an optionally substituted C9alkylene. In some cases, S2is an optionally substituted C10alkylene. In some cases, S2is an optionally substituted C11alkylene. In some cases, S2is an optionally substituted C12alkylene. In some cases, S2is an optionally substituted C13alkylene. In some cases, S2is an optionally substituted C14alkylene. In some cases, S2is an optionally substituted C15alkylene. In some cases, S2is an optionally substituted C16alkylene. In some cases, S2is an optionally substituted C17alkylene. In some cases, S2is an optionally substituted C18alkylene. In some cases, S2is an optionally substituted C19alkylene. In some cases, S2is an optionally substituted C20alkylene. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, or –C(O)–. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by –N(R20)–. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by –N(R20)C(O)–. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by –C(O)N(R20)–. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by –C(O)–. In some cases, the one or more alkylene units of the alkylene of S2are optionally and independently replaced by –O–. In some cases, if an alkylene unit of the alkylene is replaced, the alkylene may be referred to as a resulting alkylene. In some cases, if two or more of the alkylene units of S2are replaced, the replaced alkylene units are not adjacent alkylene units. In some cases, if two or more of the alkylene units of S2are replaced, the adjacent alkylene units of the resulting alkylene are not replaced. In some cases, if two or more of the alkylene units of S2are replaced, the resulting alkylene has no repeating heteroatoms of adjacent alkylene units. In some cases, if two or more of the alkylene units of S2are replaced, the resulting alkylene has no repeating of the same heteroatoms of adjacent alkylene units. In some cases, if two or more of the alkylene units of S2are replaced, the resulting alkylene unit has no - N-N- or -O-O-. In some cases, if two or more of the alkylene units of S2are replaced, the resulting alkylene unit is a stable alkylene. In some cases, if two or more of the alkylene units of S2are replaced, the resulting alkylene unit is an unreactive alkylene. In some cases, the resultingwherein the 2 heteroatoms are different from each other. In some cases, the resulting alkylene has only 2 heteroatoms, wherein the 2 heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only 3 heteroatoms, wherein the 3 heteroatoms are not adjacent to each other. In some cases, the resulting alkylene has only 4 heteroatoms, wherein the 4 heteroatoms are not adjacent to each other. In some cases, the alkylene has 0 replaced units. In some cases, the alkylene has 1 replaced unit. In some cases, the alkylene has 2 replaced units. In some cases, the alkylene has 3 replaced units. In some cases, the alkylene has 4 replaced units. In some cases, the alkylene has 5 replaced units. In some cases, the optional substituents on S2, are independently selected at each occurrence from halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, - C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle. In some cases, the optional substituents on S2, are independently selected at each occurrence from halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN. In some cases, the optional substituents on S2, are independently selected at each occurrence from: halogen, -OR30, -N(R30)2, =O, and -CN. In some cases, the optional substituents on S2, are independently selected at each occurrence from: =O. In some cases, two heteroatoms can be present in a resulting alkylene if they come from a singular replaced alkylene unit. In some cases, two heteroatoms can be present in a resulting alkylene if they come from a singular replaced alkylene unit. In some cases, a resulting alkylene has two heteroatoms, the two heteroatoms are from a singular replaced alkylene unit. In some cases, there are two heteroatoms in a resulting alkylene if they result from a singular replacement of an alkylene unit.

[0164] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-III), Formula (X-III-A), Formula (X-III-Aa), or Formula (X-III-Aaa), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-III), or Formula (XX-III-A), S2isthe C8-C12alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –O–, and –C(O)–. In some cases, S2is selected from

[0165] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-III), Formula (X-III-A), Formula (X-III-Aa), or Formula (X-III-Aaa), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-III), or Formula (XX-III-A), S2is a linear alkylene.

[0166] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-III), Formula (X-III-A), Formula (X-III-Aa), or Formula (X-III-Aaa), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-III), or Formula (XX-III-A), S2is

[0167] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-III), Formula (X-III-A), Formula (X-III-Aa), or Formula (X-III-Aaa), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-III), or Formula (XX-III-A), S1-S2is..

[0168] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-III), or Formula (X-III-A), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX- II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-III), or Formula (XX-III-A), S3isselected from a spacer. In some cases, the spacer is a divalent moiety that covalently binds twocomponents of the conjugate or Drug-Linker. In some cases, S3is present. In some cases, S3is absent. In some cases, the spacer is selected from: alkylene, heteroalkylene (an alkylene having one or more alkylene units replaced by at least one heteroatom selected from Si, N, O and S, with the appropriate valency); polyether such as polyalkylene glycol and typically polyethylene glycol; one or more natural or non-natural aminoacids such as glycine, alanine, proline, valine, N- methylglycine; C3-C8heterocyclo; C3-C8carbocyclo; arylene, and any combination thereof. In some cases, a spacer is a divalent linear alkylene group. In some cases, the spacer can be selected from the group consisting of –C1-C10alkylene-, –C1-C10heteroalkylene-, -C3- C8carbocyclo-, -O-(C1C8alkyl)-, -arylene-, –C1-C10alkylene-arylene-, -arylene-C1- C10alkylene-, –C1-C10alkylene-(C3-C8carbocyclo)-, -(C3-C8carbocyclo)-C1-C10alkylene-, -C3- C8heterocyclo-, –C1-C10alkylene-(C3-C8heterocyclo)-, -(C3-C8heterocyclo)–C1-C10alkylene-, –C1-C10alkylene-C(=O)-, –C1- C10heteroalkylene-C(=O)-, -C3-C8carbocyclo-C(=O)-, -O-(C1- C8alkyl)-C(=O)-, -arylene-C(=O)-, -C1-C10alkylene-arylene-C(=O)-, -arylene-C1-C10alkylene- C(=O)-, -C1- C10alkylene-(C3-C8carbocyclo)-C(=O)-, -(C3-C8carbocyclo)-C1-C10alkylene- C(=O)-, - C3-C8heterocyclo-C(=O)-, -C1-C10alkylene-(C3-C8heterocyclo)-C(=O)-, -(C3- C h t l ) C C lk l C( O) C C lk l NH C C h t lk l NHarylene-C1-C10alkylene-NH-, -C1-C10alkylene-(C3-C8carbocyclo)-NH-, - (C3-C8carbocyclo)- C1-C10alkylene-NH-, -C3-C8heterocyclo-NH-, -C1-C10alkylene-(C3- C8heterocyclo)-NH-, -(C3- C8heterocyclo)-C1-C10alkylene-NH-, -C1-C10alkylene-S-, - C1-C10heteroalkylene-S -, -C3- C8carbocyclo-S -, -O-(C1-C8alkyl)-)-S -, -arylene-S-, -C1- C10alkylene-arylene-S-, -arylene-C1- C10alkylene-S-, -C1-C10alkylene-(C3- C8carbocyclo)-S-, -(C3-C8carbocyclo)-C1-C10alkylene- S-, -C3-C8heterocyclo-S-, -C1- C10alkylene-(C3-C8heterocyclo)-S-, -(C3-C8heterocyclo)-C1- C10alkylene-S-, –C1-C10alkylene-O-C(=O)-, -C3-C8carbocyclo-O-C(=O)-, -O-(C1-C8alkyl)-O- C(=O)-, -arylene- O-C(=O)-, -C1-C10alkylene-arylene-O-C(=O)-, -arylene-C1-C10alkylene-O- C(=O)-, -C1- C10alkylene-(C3-C8carbocyclo)-O-C(=O)-,-(C3-C8carbocyclo)-C1-C10alkylene-O- C(=O)-, -C3-C8heterocyclo-O-C(=O)-, -C1-C10alkylene-(C3-C8heterocyclo)-O-C(=O)-, and - (C3-C8heterocyclo)-C1-C10alkylene-O-C(=O)-. In some cases, S3is optionally substituted with one or more of the substituents selected from (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, - C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -O-S(O)2R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, - OC(O)R30, -S(O)R30, -S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl. In some cases, S3is optionally substituted with one or more of the substituents selected from (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -O-S(O)2R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN. In some cases, S3is unsubstituted. In some cases, S3is substituted. In some cases, S3is a phenylene. In some cases,.

[0169] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-III), or Formula (X-III-A), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-III), or Formula (XX-III-A), S3is present and is a phenylene.

[0170] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-III), or Formula (X-III-A), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX- II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-III), or Formula (XX-III-A), S3is absent.

[0171] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, – N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–. In some embodiments, S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, or –S(O)2–. In some embodiments, S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–. In some embodiments, S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, – C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–. In some embodiments, S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–,substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, or – S(O)2–. In some embodiments, S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–.

[0172] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by -C(O)-.

[0173] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), S4is selected from an optionally substituted C1-C6alkylene wherein one or more alkylene units of the C1-C6alkylene are optionally and independently replaced by –C(O)–. In some cases, S4is selected from an optionally substituted C1-C2alkylene wherein one or more alkylene units of the C1-C2alkylene are optionally and independently replaced by –C(O)–. In some cases, S4is selected fromIn some cases, S4is selected from,. , .

[0174] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), S4is selected from – N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, – OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, and –P(O)(R20)2–. In some cases, S4is selected from –NH–, –NHC(O)–, –C(O)NH–, –NHS(O)2–, – S(O)2NH–, – O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, and – P(O)(R20)2–. In some cases, S4is selected from –NH–, –NHC(O)–, –C(O)NH–, and –C(O)–. In some cases, S4is selected from –NHC(O)–, –C(O)NH–, and –C(O)–. In some cases, S4is selected from –C(O)–.

[0175] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), S4is selected from -embodiments, S4is selected from -C1-C4alkylene-C(O)-. In some embodiments, S4is selected from -C1-C3alkylene-C(O)-. In some embodiments, S4is selected from -C1-C2alkylene-C(O)-. In some embodiments, S4is selected from -C2alkylene-C(O)-. In some embodiments, S4is -C1alkylene-C(O)-.

[0176] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–. In some cases, S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–. In some cases, S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–. In some cases, S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–. In some cases, S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–. In some cases, S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, – S(O)–, or –S(O)2–. In some cases, S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally andcases, S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –C(O)– , –OC(O)–, –C(O)O–, –N(R20)–, or –C(O)N(R20)–. In some cases, S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –C(O)–, –OC(O)–, –C(O)O–, or – C(O)N(R20)–. In some cases, S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –C(O)– or –C(O)N(R20)–. In some cases, S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –C(O)–. In some cases, S4is absent or selected from an optionally substituted C1-C6alkylene wherein one or more alkylene units of the C1-C6alkylene are optionally and independently replaced by –C(O)–. In some cases, S4is absent or selected from an optionally substituted C1-C2alkylene wherein one or more alkylene units of the C1-C2alkylene are optionally and independently replaced by –C(O)–. In some cases, S4is absent or selected from, , , . In some cases, S4is selected from, , . In some cases, S4is absent or selected from, , . In some cases, S4is selected from.

[0177] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III-Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, – N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–. In some cases, S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, or –S(O)2–. In some cases, S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, – OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–. In some cases, S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, – OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–. In some cases, S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, – S–, –S(O)–, or –S(O)2–. In some cases, S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–. In some cases, S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –C(O)–, – OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–. In some cases, S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –C(O)–, –OC(O)–, –C(O)O–, –N(R20)–, or – C(O)N(R20)–. In some cases, S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –C(O)–, –OC(O)–, –C(O)O–, or –C(O)N(R20)–. In some cases, S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –C(O)– or –C(O)N(R20)–. In some cases, S4is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –C(O)–. In some cases, S4is selected from an optionally substituted C1-C6alkylene wherein one or more alkylene units of theselected from an optionally substituted C1-C2alkylene wherein one or more alkylene units of the C1-C2alkylene are optionally and independently replaced by –C(O)–. In some cases, S4is selected from, , , . In some cases, S4is selectedand. , . , . cases, S4is. , .

[0178] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), S4is absent or selected from –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, – C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, and – P(O)(R20)2–. In some cases, S4is absent or selected from –NH–, –NHC(O)–, –C(O)NH–, – NHS(O)2–, – S(O)2NH–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6- membered heterocyclene, and –P(O)(R20)2–. In some cases, S4is absent or selected from – N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, and –C(O)–. In some cases, S4is absent or selected from –NH–, –NHC(O)–, –C(O)NH–, and –C(O)–. In some cases, S4is absent or selected from – NHC(O)–, –C(O)NH–, and –C(O)–. In some cases, S4is absent or –C(O)–. In some cases, S4is absent or selected from –N(R20)C(O)– and –C(O)N(R20)–. In some cases, S4is absent or selected from –N(R20)–.

[0179] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba),Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), S4is selected from – N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, – OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, and –P(O)(R20)2–. In some cases, S4is selected from –NH–, –NHC(O)–, –C(O)NH–, –NHS(O)2–, – S(O)2NH–, – O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, and – P(O)(R20)2–. In some cases, S4is selected from –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, and – C(O)–. In some cases, S4is selected from –NH–, –NHC(O)–, –C(O)NH–, and –C(O)–. In some cases, S4is selected from –NHC(O)–, –C(O)NH–, and –C(O)–. In some cases, S4is –C(O)–. In some cases, S4is selected from –N(R20)C(O)– and –C(O)N(R20)–. In some cases, S4is selected from –N(R20)–.

[0180] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), S4is absent or selected from -C1-C6alkylene-C(O)-. In some cases, S4is absent or selected from -C1-C5alkylene-C(O)-. In some cases, S4is absent or selected from -C1-C4alkylene-C(O)-. In some embodiments, S4is absent or selected from -C1-C3alkylene-C(O)-. In some cases, S4is absent or selected from -C1-C2alkylene-C(O)-. In some embodiments, S4is absent or selected from -C2alkylene-C(O)-. In some cases, S4is absent or -C1alkylene-C(O)-. In some embodiments, S4is absent or -C(O)-.

[0181] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba),Formula (X-III-A), Formula (X-III-Aa), or Formula (X-III-Aaa), S1-S2-M1is selected from,, wherein S3is absent. In some cases,

[0182] In some embodiments, Formula (X), Formula (X-I), Formula (X-I-A), or Formula (X-I-B) is represented by the structure of Formula (X-I-Ba)Formula (X-I-Ba), or a pharmaceutically acceptable salt thereof.

[0183] In some embodiments, Formula (X), Formula (X-I), Formula (X-I-A), Formula (X-I- B), or Formula (X-I-Ba) is represented by the structure of Formula (Formula X-I-Baa)or a pharmaceutically acceptable salt thereof.

[0184] In some embodiments, Formula (X), Formula (X-III), or Formula (X-III-A) is represented by the structure of Formula (X-III-Aa)or a pharmaceutically acceptable salt thereof.

[0185] In some embodiments, Formula (X), Formula (X-III), Formula (X-III-A), or Formula (X-III-Aa) is represented by the structure of Formula (Formula X-III-Aaa)or a pharmaceutically acceptable salt thereof.

[0186] In some embodiments, Formula (X), Formula (X-I) or Formula (X-I-A) is represented by the structure of Formula (X-I-C)or a pharmaceutically acceptable salt thereof.

[0187] In some embodiments, Formula (X), Formula (X-I), Formula (X-I-A), or Formula (X-I-C) is represented by the structure of Formula (X-I-CB)Formula (X-I-CB), or a pharmaceutically acceptable salt thereof.

[0188] In some embodiments, Formula (X), Formula (X-II), or Formula (X-II-A) is represented by the structure of Formula (X-II-C)Formula (X-II-C), or a pharmaceutically acceptable salt thereof.

[0189] In some embodiments, Formula (X), Formula (X-II), Formula (X-II-A), or Formula (X-II-C) is represented by the structure of Formula (X-II-CB)Formula (X-II-CB), or a pharmaceutically acceptable salt thereof.

[0190] In some embodiments, Formula (X), Formula (X-I), Formula (X-I-A), Formula (X- II), Formula (X-II-A), Formula (X-III), or Formula (X-III-A) is represented by the structure of Formula (X-III-C)Formula (X-III-C), or a pharmaceutically acceptable salt thereof.

[0191] In some embodiments, Formula (X), Formula (X-I), or Formula (X-I-A) is represented by the structure of Formula (X-I-D)Formula (X-I-D), or a pharmaceutically acceptable salt thereof.

[0192] In some embodiments, Formula (X), Formula (X-I), Formula (X-I-A), or Formula (X-I-D) is represented by the structure of Formula (X-I-DB)Formula (X-I-DB), or a pharmaceutically acceptable salt thereof.

[0193] In some embodiments, Formula (X), Formula (X-II), or Formula (X-II-A) is represented by the structure of Formula (X-II-D)Formula (X-II-D), or a pharmaceutically acceptable salt thereof.

[0194] In some embodiments, Formula (X), Formula (X-II), Formula (X-II-A), or Formula (X-II-D) is represented by the structure of Formula (X-II-DB)Formula (X-II-DB), or a pharmaceutically acceptable salt thereof.

[0195] In some embodiments, Formula (X), Formula (X-I), Formula (X-I-A), Formula (X- II), Formula (X-II-A), Formula (X-III), or Formula (X-III-A) is represented by the structure of Formula (X-III-D)Formula (X-III-D), or a pharmaceutically acceptable salt thereof.

[0196] In some embodiments, Formula (XX) Formula (XX-I), or Formula (XX-I-A) is represented by the structure of Formula (XX-I-Aa)Formula (XX-I-Aa), or a pharmaceutically acceptable salt thereof.

[0197] In some embodiments, Formula (XX) Formula (XX-I), or Formula (XX-I-A) is represented by the structure of Formula (XX-I-Ab)Formula (XX-I-Ab), or a pharmaceutically acceptable salt thereof.

[0198] In some embodiments, Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-II), Formula (XX-II-A), Formula (XX-III), or Formula (XX-III-A) is represented by the structure of Formula (XX-III-Aa)or a pharmaceutically acceptable salt thereof.

[0199] In some embodiments, Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-II), Formula (XX-II-A), Formula (XX-III), or Formula (XX-III-A) is represented by the structure of Formula (XX-III-Ab)Formula (XX-III-Ab), or a pharmaceutically acceptable salt thereof.

[0200] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), or Formula (XXX-II), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-C), Formula (X-I-D), Formula (X-II), Formula (X-II-A), Formula (X-II-C), or Formula (X-II-D ), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-I-C), Formula (XX-II), or Formula (XX-II-A), X is CH.

[0201] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), or Formula (XXX-II), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-C), Formula (X-I-D), Formula (X-II), Formula (X-II-A), Formula (X-II-C), or Formula (X-II-D ), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-I-C), Formula (XX-II), or Formula (XX-II-A), X is N.

[0202] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-I-C), Formula (XX-III-Aa), or Formula (XX-III-Ab), Y-is selected from KB. In some cases, KBis selected from a peptide unit, -OS(O)2(OR30)2, and - OP(O)(OR30)2; and phenyl which is optionally substituted with one or more substituents independently selected from -S(O)2R30, -OS(O)2OR30, -P(O)(OR30)2, and -OP(O)(OR30)2. Insome cases, Y-S4-K1 is selected fromselected from KB. In some cases, Y-S4-K1is selectedselected from KB. In some cases, Y-S4-K1is selected fromis selected from KB. In some cases, KBis selected from a peptide unit. In some cases, the peptide unit is represented bym is selected from 1 to 3; n is selected from 1 to 30; each R5is independently selected from hydrogen and C1-6alkyl;each R10is independently selected from hydrogen, methyl, isopropyl, isobutyl, sec-butyl, benzyl, p-hydroxybenzyl, -CH2OH, -CH(OH)CH3, -CH2CH2SCH3, -CH2CONH2, - CH2COOH, -CH2CH2CONH2, -CH2CH2COOH, -CH2CH2CH2COOH, - (CH2)3NHC(=NH)NH2, -(CH2)3NH2, -(CH2)3NHCOCH3, -(CH2)3NHCHO, - (CH2)4NHC(=NH)NH2, -(CH2)4NH2, -(CH2)4NHCOCH3, -(CH2)4NHCHO, - (CH2)3NHCONH2, -(CH2)4NHCONH2, -CH2CH2CH(OH)CH2NH2, 2-pyridylmethyl-, 3- pyridylmethyl-, 4-pyridylmethyl-, phenyl, cyclohexyl,; andT is selected fromIn some cases, each R10is selected from hydrogen, and methyl. In some cases, each peptide unit is independently represented by. In some cases, each R10is hydrogen. In some cases, each R5is independently selected from hydrogen and methyl. In some cases, each peptide unit is independently represented by12. In some cases, each n is selected from 5 to 10. In some cases, each n is selected from 7 to 12. In some cases, each n is selected from 8 to 10. In some cases, each n is 5. In some cases, each n is 6. In some cases, each n is 7. In some cases, each n is 8. In some cases, each n is 9. In somecases, n is 10. In some cases, each n is selected from 5 and 10.

[0203] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-C), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX- II-B), Formula (XX-III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab),OP(O)(OR30)2; and phenyl which is optionally substituted with one or more substituents independently selected from -S(O)2R30, -OS(O)2OR30, -P(O)(OR30)2, and -OP(O)(OR30)2. In some cases, Y-S4-K1is selected fromfis independently selected fromeach K1is independently selected from KL. In some cases, each Y-S4-K1is independently selected fromeach K1is independently selected from KL. In some cases, KLis selected from a peptide unit. In some cases, the peptide unit is represented bym is selected from 1 to 3; n is selected from 1 to 30; each R5is independently selected from hydrogen and C1-6alkyl; each R10is independently selected from hydrogen, methyl, isopropyl, isobutyl, sec-butyl, benzyl, p-hydroxybenzyl, -CH2OH, -CH(OH)CH3, -CH2CH2SCH3, -CH2CONH2, - CH2COOH, -CH2CH2CONH2, -CH2CH2COOH, -CH2CH2CH2COOH, - (CH2)3NHC(=NH)NH2, -(CH2)3NH2, -(CH2)3NHCOCH3, -(CH2)3NHCHO, - (CH2)4NHC(=NH)NH2, -(CH2)4NH2, -(CH2)4NHCOCH3, -(CH2)4NHCHO, - (CH2)3NHCONH2, -(CH2)4NHCONH2, -CH2CH2CH(OH)CH2NH2, 2-pyridylmethyl-, 3- pyridylmethyl-, 4-pyridylmethyl-, phenyl, cyclohexyl,; andIn some cases, each R10is selected from hydrogen, and methyl. In some cases, the peptide unit is represented by. In some cases, each R10is hydrogen. In some cases, each R5is independently selected fromhydrogen and methyl. In some cases, each peptide unit is independently represented by. , n is selected from 5 to 12. In some cases, each n is selected from 5 to 10. In some cases, each n is selected from 7 to 12. In some cases, each n is selected from 8 to 10. In some cases, each n is 5. In some cases, each n is 6. In some cases, each n is 7. In some cases, each n is 8. In some cases, each n is9. In some cases, n is 10. In some cases, each n is selected from 5 and 10.

[0204] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III) Formula (XX III A) Formula (XX III Aa) Formula (XX I C) or Formula (XX III Ab)cleavage of the cleavable unit triggers self -immolation of the phenyl-comprising linker of thecompounds of the invention, and release of the Drug unit (D).

[0205] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), the sugar cleavable unit can refer to a sugar moiety, preferably a glucuronide or a galactoside. In some cases, the sugar cleavable unit is glucuronide or a glucuronide derivative. In some cases, the sugar cleavable unit is glucuronide. In some cases, the sugar cleavable unit is galactoside or a galactoside derivative. In some cases, the sugar cleavable unit is galactoside.

[0206] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), the sugar cleavable unit of T1includes a sugar. In some cases, the sugar is glucuronide. 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.

[0207] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB),Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (. In some cases, Y is a sugar moiety. In some cases, Y is absent. In some cases, the sugar moiety further comprises at least one -S4-K1or -K1(i.e., if S4is absent). In some cases, the sugar moiety further comprises at least one -S4-K1. In some cases, the sugar moiety further comprises at least one -K1. In some cases, the sugar moiety further comprises one -S4-K1. In some cases, the sugar moiety further comprises one -K1.

[0208] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), Formula (XX-I-C), or Formula (XX-III-Ab), the peptide cleavable unit can refer to a polypeptide, preferably a dipeptide or a tripeptide. In some cases, the peptide cleavable unit is selected from dipeptide. In some cases, the peptide cleavable unit is selected from a tripeptide. In some cases, the peptide cleavable unit is selected from a tetrapeptide. In some cases, the peptide cleavable unit further comprises at least one -S4- K1or -K1(i.e., if S4is absent). In some cases, the peptide cleavable unit further comprises at least one -S4-K1. In some cases, the peptide cleavable unit further comprises at least one -K1. In some cases, the peptide cleavable unit further comprises one -S4-K1. In some cases, the peptide cleavable unit further comprises one -K1. In some cases, K1is selected from KBand KL. In some cases, the peptide cleavable unit further comprises at least one -S4-KB, -S4-KL, -KB, or -KL(i.e., if S4is absent). In some cases, K1is selected from KB. In some cases, K1is selected from KL. In some cases, the peptide cleavable unit further comprises at least one -S4-KBor -KB(i.e., if S4is absent) In some cases the peptide cleavable unit further comprises at least one -S4-KLor -KL(i.e., if S4is absent). In some cases, S4-K1is selected from S4-KB. In some cases, -K1is selected from -KB. In some cases, S4-K1is selected from S4-KLIn some cases, -K1is selected from -KL.

[0209] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), the peptide unit of T2includes one or more amino acids selected from a group consisting of 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, the peptide unit of T2includes one or more amino acids selected from a group consisting of alanine, arginine, asparagine, aspartic acid, glutamine, glycine, lysine, methionine, phenylalanine, proline, serine, valine, citrulline, and β-Alanine. In some cases, the peptide unit of T2includes a dipeptide or tripeptide. In some cases, the peptide unit of T2includes a dipeptide. In some cases, the dipeptide is selected from Val-Cit, Val-Ala and Phe-Lys. In some cases, the peptide unit of T2further comprises at least one -S4-K1or -K1(i.e., if S4is absent). In some cases, the peptide unit of T2further comprises at least one -S4-K1. In some cases, the peptide unit of T2further comprises at least one -K1. In some cases, the peptide unit of T2further comprises one -S4-K1. In some cases, the peptide unit of T2further comprises one -K1. In some cases, K1is selected from KBand KL. In some cases, the peptide unit of T2further comprises at least one -S4-KB, -S4-KL, -KB, or -KL(i.e., if S4is absent). In some cases, K1is selected from KB. In some cases, K1is selected from KL. In some cases, the peptide unit of T2further comprises at least one -S4-KBor -KB(i.e., if S4is absent). In some cases, the peptide unit of T2further comprises at least one -S4-KLor -KL(i.e., if S4is absent). In some cases, S4-K1is selected from S4-KB. In some cases, -K1is selected from -KB. In some cases, S4-K1is selected from S4-KL. In some cases, -K1is selected from -KL.

[0210] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba),Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), the peptide unit of T2includes a capping moiety. In some cases, the capping moiety is a moiety capable of reacting with an amine of the peptide to form an amide, carbamate or sulfonamide. In some cases, the capping moiety is a moiety which results from reacting with an amine to form an amide, carbamate or sulfonamide. In some cases, the capping moiety is a moiety which results from reacting with an amine to form an amide. In some cases, the capping moiety is a moiety which caps the end of an peptide / amino acid. In some cases, the capping moiety is. In some cases, Y further comprises at least one -S4-K1. In some cases, Y further comprises at least one - K1. In some cases, Y1further comprises one -S4-K1. In some cases, Y1further comprises one -K1.

[0211] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), the peptide unit of T2includes a capping moiety. In some cases, the capping moiety is a moiety capable of reacting with an amine of the peptide to form an amide, carbamate or sulfonamide. In some cases, the capping moiety is a moiety which results from reacting with an amine to form an amide, carbamate or sulfonamide. In some cases, the capping moiety is a moiety which results from reacting with an amine to form an amide. In some cases, the capping moiety is a moiety which caps the end of an peptide / amino acid. In some cases, the capping moiety is an acyl moiety. In some cases, the capping moiety is, wherein R* is selected from C1-6alkyl. In somecases, the capping moiety is. In some cases, Y further comprises at least one -S4-K1. In some cases, Y further comprises at least one -K1. In some cases, Y further comprises one -S4-K1. In some cases, Y further comprises one -K1.

[0212] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), the peptide unit of T2includes one or more amino acids selected from a group consisting of 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, the peptide unit of T2includes a dipeptide, tripeptide, or tetrapeptide. In some cases, the peptide unit of T2includes a dipeptide or tripeptide. In some cases, peptide unit of T2is selected from Val-Cit, Gly-Val-Cit, Val-Ala, Gly- Val-Ala and Phe-Lys. In some cases, peptide unit of T2is selected from Val-Cit, Gly-Val-Cit, Val-Ala, and Gly-Val-Ala. In some cases, peptide unit of T2is selected from Val-Ala and Gly- Val-Ala. In some cases, peptide unit of T2is selected from Val-Cit and Gly-Val-Cit. In some cases, the peptide unit of T2has a capping moiety. In some cases, the capping moiety is selected from , wherein R* is selected from C1-6alkyl. In some cases, the capping moiety is. In some cases, the peptide unit of T2has a capping moiety, wherein the capping moiety is selected from, wherein R* is selected from C1-6alkyl. In some cases, the peptide unit of T2has a capping moiety, wherein the capping moiety is. In some cases, the peptide. cases, the peptide unit. some cases, the peptide unit of T2is. In some cases, the peptide unit of T2further comprises at least one - S4-K1. In some cases, the peptide unit of T2further comprises at least one -K1. In some cases, the peptide unit of T2further comprises one -S4-K1. In some cases, the peptide unit of T2further comprises one -K1. In some cases. K1is selected from KBand KL. In some cases. K1is selected from KB. In some cases. K1is selected KL. In some cases, the peptide unit of T2further comprises at least one -S4-KB. In some cases, the peptide unit of T2further comprises at least one -KB. In some cases, the peptide unit of T2further comprises one -S4-KB. In some cases, the peptide unit of T2further comprises one -KB. In some cases, the peptide unit of T2further comprises at least one -S4-KL. In some cases, the peptide unit of T2further comprises at least one -KL. In some cases, the peptide unit of T2further comprises one -S4-KL. In some cases, the peptide unit of T2further comprises one -KL.

[0213] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), Formula (XX-I-C), or Formula (XX-III-Ab), the peptide unit of T2further comprises at least one -S4-K1or -K1(i.e., if S4is absent). In some cases, the peptide unit of T2further comprises at least one -S4-K1. In some cases, the peptide unit of T2further comprises at least one -K1. In some cases, the peptide unit of T2further comprises one -S4-K1. In some cases, K1is selected from KBand KL. In some cases, the peptide unit of T2further comprises at least one S4KBS4KLKBor KL(ie if S4is absent) In some casesT2further comprises at least one -S4-KBor -KB(i.e., if S4is absent). In some cases, the peptide unit of T2further comprises at least one -S4-KLor -KL(i.e., if S4is absent). In some cases, S4-K1is selected from S4-KB. In some cases, each S4-K1is independently selected from S4-KB. In some cases, -K1is selected from -KB. In some cases, each -K1is independently selected from -KB. In some cases, S4-K1is selected from S4-KL. In some cases, each S4-K1is independently selected from S4-KL. In some cases, -K1is selected from -KL. In some cases, each -K1is independently selected from -KL. In some cases, the peptide unit of T2further comprises one -K1. In somecases, Y-S4-K1 is selected fromand. In some cases, Y-S4-K1is selected fromcases, Y-S4-K1 is selected from. In some cases, Y-S4-K1 is,, , ,, . In some cases, each S4is independently selected fromsome cases, S4is. In some cases, Y-S4-K1is selected from,ases, Y-S4-K1iss. ,In some cases, Y-S4-K1is selected from.In some cases, Y-S4-K1is. ,. , oiety. In some cases, K1is selected from KBand KL. In some cases, KBand KLinclude a capping moiety. In some cases, KLincludes a capping moiety. In some cases, KBincludes a capping moiety. In some cases, the capping moiety is a moiety capable of reacting with an amine of KBor KLto form an amide, carbamate or sulfonamide. In some cases, the capping moiety is a moiety which results from reacting with an amine to form an amide, carbamate or sulfonamide. In some cases, the capping moiety is a moiety which results from reacting with an amine to form an amide. In somecases, the capping moiety is a moiety which caps the end of a / an peptide / amino acid of K B orselected from , wherein R* is selected from C1-6alkyl. In some cases, the capping moiety.

[0214] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), Formula (XX-I-C), or Formula (XX-III-Ab), Y-, ,. In some cases, Y-S4-K1is selected f, .,some cases, Y-S4-K1is selected from,, and. In some cases, Y-S4-K1is selected from , , , ,,, , , , ,,some cases, Y-S4-K1 is selected from, , , ,. In some cases, Y-S4-K1is selected from, , ,. In some cases, Y-S4-K1is selected from. In some cases, Y-S4-K1is selected from. In some cases, Y-S4-K1is selected from.

[0215] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), Formula (XX-I-C), or Formula (XX-III-Ab), can have one or more -S4-K1attached to any portion of the compound. In some cases, the Drug- Linker or conjugate can have two -S4-K1attached to any portion of the compound. In some cases, the Drug-Linker or conjugate can have three -S4-K1attached to any portion of the compound. In some cases, the Drug-Linker or conjugate can have four -S4-K1attached to any portion of the compound. In some cases, the Drug-Linker or conjugate can have four -S4-K1attached to any portion of the compound. In some cases, the Drug-Linker or conjugate can have five -S4-K1attached to any portion of the compound. In some cases, the Drug-Linker or conjugate can have six -S4-K1attached to any portion of the compound.

[0216] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- A ) F l (X III A ) F l (X III C) F l (X III D) f j t lt fFormula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), have at least one or more additional -S4-K1attached to Y. In some cases, the Drug-Linker or conjugate have at least two or more additional -S4-K1attached to Y. In some cases, the Drug-Linker or conjugate have at least three or more additional -S4-K1attached to Y. In some cases, the Drug-Linker or conjugate has one -S4-K1attached to Y. In some cases, the Drug-Linker or conjugate has two - S4-K1attached to Y. In some cases, the Drug-Linker or conjugate has three -S4-K1attached to Y.

[0217] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), Formula (XX-I-C), or Formula (XX-III-Ab), K1is selected from KBand KL. In some cases, K1is selected from KB. In some cases, K1is selected from KL. In some cases, Y-S4-K1is selected from Y-S4-KB, Y-S4-KL, Y-KBand Y-KL. In some cases, Y-S4-K1is selected from Y-KBand Y-KL. In some cases, Y-S4-K1is selected from Y-S4-KB. In some cases, Y-S4-K1is selected from Y-S4-KL. In some cases Y-S4-K1is selected from Y-S4-KBand Y-KL. In some cases Y-S4-K1is selected from Y-S4-KBand Y-KL, and Y-S4-KL. In some cases, S4is absent. In some cases, S4is absent or selected from.Insome cases, S4is absent or selected from, , . In some cases, S4is selected from, , . In some cases, S4is. so e cases, s . In some cases, S4is.

[0218] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for aFormula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-III), Formula (X-III-A), or Formula (X-III-Aa), M1is a group which can react with a Targeting Unit to form a connector unit. In some cases, a group that can react with a Targeting Unit to form a connector unit refers to any chemical moiety that is being reactive for covalently binding a Targeting Unit (e.g., antibody, ligand, antigen-binding fragment). In some cases, it may react with a thiol group present on a Targeting Unit. In some cases, it may react with a thiol group present on an antibody or antigen-binding fragment thereof. In some cases, it may react with a thiol group present on a ligand. In some cases, the chemical moieties that are being reactive for covalently binding a ligand includes: carboxylic acid; primary amine; secondary amine; tertiary amine; hydroxyl; halogen; activated ester such as N-hydroxysuccinimide ester, perfluorinated esters, nitrophenyl esters, aza-benzotriazole and benzotriazole activated ester, acylureas; alkynyl; alkenyl; azide; isocyanate; isothiocyanate; aldehyde; thiol- reactive moieties such as maleimide, halomaleimides, haloacetyls, pyridyl disulfides; thiol; acrylate; mesylate; tosylate; triflate, hydroxylamine; chlorosulfonyl; boronic acid - B(OR’)2derivatives wherein R’ is hydrogen or alkyl group. In some cases, M1is selected from maleimide, halogen, COOH,, azide, , activated group ,, OH, SH, activated disulfide group, NH2, and -ONH2. In some cases, M1is selected from maleimide, halogen,, azide,, OH, SH, activated disulfide group, NH2, and -ONH2. In some cases, M1is maleimide. In some cases, M1is halogen. In some cases, M1is COOH. In some cases, M1is. some cases, M1is azide. In some cases,. some cases, M1is OH. In some cases, M1is SH. In some cases, the activated disulfide group of M1isselected from. In some cases, M1is. In some cases, M1is NH2. In some cases, M1is -ONH2. In some cases, M1is selected fromsome cases, M1is selected fromIn some cases, M1is azide. In some cases, M1is. In some cases, the activated group of M1is selected fromsome cases,.

[0219] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III-Aa), Formula (X-III- C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-III), Formula (XX-III-A), Formula (XX- III-Aa), Formula (XX-I-C), or Formula (XX-III-Ab), D is drug unit. In some cases, D includes a spacer. In some cases, the spacer is a divalent moiety that covalently attaches the drug to theof the molecule. In some cases, D does not include a spacer. In some cases, the spacer can be selected from the group consisting of –C1-C10alkylene-, –C1-C10heteroalkylene-, -C3- C8carbocyclo-, -O-(C1C8alkyl)-, -arylene-, –C1-C10alkylene-arylene-, -arylene-C1- C10alkylene-, –C1-C10alkylene-(C3-C8carbocyclo)-, -(C3-C8carbocyclo)-C1-C10alkylene-, -C3- C8heterocyclo-, –C1-C10alkylene-(C3-C8heterocyclo)-, -(C3-C8heterocyclo)–C1-C10alkylene-, –C1-C10alkylene-C(=O)-, –C1-C10heteroalkylene-C(=O)-, -C3-C8carbocyclo-C(=O)-, -O-(C1- C8alkyl)-C(=O)-, -arylene-C(=O)-, -C1-C10alkylene-arylene-C(=O)-, -arylene-C1-C10alkylene- C(=O)-, -C1- C10alkylene-(C3-C8carbocyclo)-C(=O)-, -(C3-C8carbocyclo)-C1-C10alkylene- C(=O)-, - C3-C8heterocyclo-C(=O)-, -C1-C10alkylene-(C3-C8heterocyclo)-C(=O)-, -(C3- C8heterocyclo)-C1-C10alkylene-C(=O)-, -C1-C10alkylene-NH-, -C1-C10heteroalkylene-NH-, - C3-C8carbocyclo-NH-, -O-(C1-C8alkyl)-NH-, -arylene-NH-, -C1-C10alkylene- arylene-NH-, - arylene-C1-C10alkylene-NH-, -C1-C10alkylene-(C3-C8carbocyclo)-NH-, - (C3-C8carbocyclo)- C1-C10alkylene-NH-, -C3-C8heterocyclo-NH-, -C1-C10alkylene-(C3- C8heterocyclo)-NH-, -(C3- C8heterocyclo)-C1-C10alkylene-NH-, -C1-C10alkylene-S-, - C1-C10heteroalkylene-S -, -C3- C8carbocyclo-S -, -O-(C1-C8alkyl)-)-S-, -arylene-S-, -C1- C10alkylene-arylene-S-, -arylene-C1- C10alkylene-S-, -C1-C10alkylene-(C3- C8carbocyclo)-S-, -(C3-C8carbocyclo)-C1-C10alkylene- S-, -C3-C8heterocyclo-S-, -C1- C10alkylene-(C3-C8heterocyclo)-S-, -(C3-C8heterocyclo)-C1- C10alkylene-S-, –C1-C10alkylene-O-C(=O)-, -C3-C8carbocyclo-O-C(=O)-, -O-(C1-C8alkyl)-O- C(=O)-, -arylene- O-C(=O)-, -C1-C10alkylene-arylene-O-C(=O)-, -arylene-C1-C10alkylene-O- C(=O)-, -C1- C10alkylene-(C3-C8carbocyclo)-O-C(=O)-,-(C3-C8carbocyclo)-C1-C10alkylene-O- C(=O)-, -C3-C8heterocyclo-O-C(=O)-, -C1-C10alkylene-(C3-C8heterocyclo)-O-C(=O)-, and - (C3-C8heterocyclo)-C1-C10alkylene-O-C(=O)-. In some cases, the spacer can be selected from the group consisting of –C1-C10alkylene-, and -C1-C10alkylene-NH-. In some cases, the drug unit is only a drug.

[0220] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III-Aa), Formula (X-III- C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-III), Formula (XX-III-A), Formula (XX- III-Aa), Formula (XX-I-C), or Formula (XX-III-Ab), D is selected from a Drug unit. In someDrug unit is a drug and a spacer. In some cases, the Drug unit is selected from an alkylating agent, a cytotoxic agent, an immune modulatory agent, a nucleic acid, a growth inhibitory agent, a PROTAC, a toxin, a radioactive isotope, a chelating ligand, and a chelating ligand comprising a radioactive isotope. In some cases, the Drug unit is selected from a cytotoxic agent. In some cases, the Drug unit is selected from an alkylating agent, a cytotoxic agent, an immune modulatory agent, a growth inhibitory agent. In some cases, each Drug unit is independently selected from an alkylating agent, a cytotoxic agent, an immune modulatory agent, a growthinhibitory agent. In some cases, the Drug unit is selected from an alkylating agent. In somecases, the Drug unit is selected from an alkylating agent. In some cases, the Drug unit is selected from a cytotoxic agent. In some cases, the Drug unit is selected from an immune modulatory agent. In some cases, the Drug unit is selected from a growth inhibitory agent. In some cases, the agent is a small molecule agent. In some cases, the agent is a peptide-based agent. In some cases, the agent is a small molecule agent, a peptide-based agent, or a combination thereof. In some cases, each Drug unit is independently selected from an alkylating agent. In some cases, each Drug unit is independently selected from a cytotoxic agent. In some cases, the Drug unit is selected from an immune modulatory agent. In some cases, each Drug unit is independently selected from a growth inhibitory agent. In some cases, each agent is independently a small molecule agent. In some cases, each agent is independently a peptide-based agent. In some cases, each agent is independently a small molecule agent, a peptide-based agent, or a combination thereof.

[0221] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III-Aa), Formula (X-III- C), or Formula (X-III-D), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX-III), Formula (XX-III-A), Formula (XX- III-Aa), Formula (XX-I-C), or Formula (XX-III-Ab), D is selected from a Drug unit. 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. In some cases, the Drug unit (D) is selected from an alkylating agent, a bizelesin derivative, a cytotoxic agent, camptothecin derivative, a growth inhibitory agent, a monomethyl auristatin derivative (e.g. MMAE, MMAF, and the like) and an immunealkylating agent, a bizelesin derivative, a cytotoxic agent, camptothecin derivative, a growth inhibitory agent, a monomethyl auristatin derivative (e.g. MMAE, MMAF, and the like) and an immune modulatory agent. In some cases, the Drug unit is selected from a bizelesin derivative, camptothecin derivative, and a monomethyl auristatin derivative (e.g. MMAE, MMAF, and the like). In some cases, each Drug unit is independently selected from a bizelesin derivative, camptothecin derivative, and a monomethyl auristatin derivative (e.g. MMAE, MMAF, and the like). In some cases, the Drug unit is selected from an alkylating agent, a bizelesin derivative, a cytotoxic agent, camptothecin derivative, a growth inhibitory agent, and a monomethyl auristatin derivative (e.g. MMAE, MMAF, and the like). In some cases, each Drug unit is independently selected from an alkylating agent, a bizelesin derivative, a cytotoxic agent, camptothecin derivative, a growth inhibitory agent, and a monomethyl auristatin derivative (e.g. MMAE, MMAF, and the like). In some cases, the Drug unit is selected from an alkylating agent and a bizelesin derivative. In some cases, each Drug unit is independently selected from an alkylating agent and a bizelesin derivative. In some cases, the Drug unit is selected from a cytotoxic agent and camptothecin derivative. In some cases, each Drug unit is independently selected from a cytotoxic agent and camptothecin derivative. In some cases, the Drug unit is selected from camptothecin derivative and a growth inhibitory agent. In some cases, each Drug unit is independently selected from camptothecin derivative and a growth inhibitory agent. In some cases, the Drug unit is selected from a growth inhibitory agent and a monomethyl auristatin derivative (e.g. MMAE, MMAF, and the like). In some cases, each Drug unit is independently selected from a growth inhibitory agent and a monomethyl auristatin derivative (e.g. MMAE, MMAF, and the like). In some cases, the Drug unit is selected from an immune modulatory agent. In some cases, the agent is a small molecule agent. In some cases, the agent is a peptide-based agent. In some cases, the agent is a small molecule agent, a peptide-based agent, or a combination thereof. In some cases, the Drug unit is selected from exatecan, SN-38, monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), and bizelesin. In some cases, each Drug unit is independently selected from exatecan, SN-38, monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), and bizelesin. In some cases, the Drug unit is selected from a camptothecin derivative, a bizelesin derivative, and a monomethyl auristatin derivative (e.g. MMAE, MMAF, and the like). In some cases, Drug unit is a camptothecin derivative. In some cases, Drug unit is exatecan. In some cases, Drug unit is SN-38. In some cases, the Drug unit is a bizelesin derivative. In some cases, the Drug unit is bizelesin. In some cases, the Drug unit is a monomethyl auristatin derivative (e.g. MMAE, MMAF, and the like). In some cases, Drug unit is selected from MMAF and MMAE. In some cases, the Drug unit isand bizelesin. In some cases, the Drug unit is selected form exatecan, monomethyl auristatin E (MMAE), and bizelesin. In some cases, the Drug unit is selected from monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), and bizelesin. In some cases, the Drug unit is selected from exatecan, SN-38, and bizelesin. In some cases, the Drug unit is exatecan. In some cases, the Drug unit is SN-38. In some cases, the Drug unit is monomethyl auristatin E (MMAE). In some cases, the Drug unit is monomethyl auristatin F (MMAF). In some cases, the Drug unit is bizelesin. In some cases, the cytotoxic agent is selected from an auristatin, a maytansinoid, a camptothecin, a duocarmycin, and a calicheamicin. In some cases, a cytotoxic agent is an agent that has a cytotoxic effect on a cell. In some cases, cytotoxic agents include, for example, tubulin disrupting agents, topoisomerase inhibitors, DNA minor groove binders, and DNA alkylating agents. In some cases, an alkylating agent is a DNA alkylating agent. In some cases, the DNA alkylating is selected from a bizelesin derivative. In some cases, the DNA alkylating is bizelesin. In some cases, tubulin disrupting agents include, for example, auristatins, dolastatins, tubulysins, colchicines, vinca alkaloids, taxanes, cryptophycins, maytansinoids, hemiasterlins, as well as other tubulin disrupting agents. In some cases, auristatins are derivatives of the natural product dolastatin 10. In some cases, auristatins are selected from MMAE (N-methylvaline-valine-dolaisoleuine-dolaproine-norephedrine), MMAF (N-methylvaline-valine-dolaisoleuine-dolaproine-phenylalanine) and AFP. In some cases, a cytotoxic agent can be a topoisomerase inhibitor. In some cases, a drug is an immune modulatory agent, such as a TLR7 and / or TLR8 agonist. In some cases, a drug is a proteolysis targeted chimera (PROTAC). In some cases, the drug is selected from exatecan, MMAE, MMAF, duocarmycin, SN-38, and dxd. In some cases, the drug is selected from MMAE, MMAF, duocarmycin, SN-38, and dxd. In some cases, an immune modulatory agent is a STING agonist. In some cases, a drug is a radioactive atom. In some cases, a drug is a chelate, wherein the chelate comprises a radioactive atom. In some cases, a drug is a proteolysis targeted chimera (PROTAC). In some cases, D is selected from,. , d. ,.

[0222] In some embodiments, for a Linker or salt of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXX-III), or Formula (XXX-III-A), or for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III- Aa), Formula (X-III-Aaa), Formula (X-III-C), Formula (XX-I-C), or Formula (X-III-D), further includes attaching a Targeting Unit to M1to form a conjugate, wherein M1of the Drug-Linker reacts and forms a covalent bond to the Targeting Unit. In some cases, the Targeting unit is selected from an antibody or an antigen-binding portion thereof. In some cases, the conjugate has an average ratio of Drug-Linker to Targeting unit of about 1 to 10. In some cases, the Targeting unit is selected from an antibody or an antigen-binding portion thereof. In some cases, the conjugate has an average ratio of Drug-Linker to Targeting unit of about 1 to 8. In some cases, the conjugate has an average ratio of Drug-Linker to Targeting unit of about 1 to 5. In some cases, the conjugate has an average ratio of Drug-Linker to Targeting unit of about 1,about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, or about 10. In some cases,

[0223] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-II), Formula (XX-II-A), Formula (XX-II- B), Formula (XX-III), or Formula (XX-III-A), M2is a connector unit selected from options herein. In some cases, the connector unit refers to a component that connects different parts of the conjugate together. In some cases, the connector unit can connect the Targeting Unit to S3(if present) or to S1. In some cases, the connector unit forms a bond with a sulfur atom of a Targeting unit. In some cases, the connector unit forms a bond with a sulfur atom of a Targeting unit via a maleimide group. In some cases, the sulfur atom can be derived from, for example, a sulfhydryl group of a Targeting unit (e.g., a thiol group of an interchain disulfide bond). In somecases, M2 is. , . , .In some cases,. In some cases, M2 is -CH2-C(O)NH-. In some cases, M2 is. In some cases, M2is . In some cases, M2is. In some cases, M2is linked to the Targeting unit via a disulfide bondbetween a sulfur atom of M2 and a sulfur atom of the Targeting unit. In some cases, M2 is .In some cases, the connector unit forms a bond with a primary or secondary amino group of a Targeting unit. . In some cases, the connector unit forms one or two bond with one or two thiol groups of a Targeting unit. In some cases. M2is selected from,

[0224] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-II), Formula (XX-II-A), Formula (XX-II- B), Formula (XX-III), or Formula

[0225] In some embodiments, for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-II), Formula (XX-II-A), Formula (XX-II- B), Formula (XX-III), or Formula (XX-III-A), M2is selected from,.

[0226] In an aspect, the present disclosure provides a Linker of Formula (XXX):Formula (XXX), or a pharmaceutically acceptable salt thereof, wherein;X is selected from CH and N; Y is selected from -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is a peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, S1, S2, S3, and S4are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-(ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl; M1is a group which can react with a ligand to form a connector unit; K1is selected from KBand KL; KBis selected from: (i) a peptide unit, (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; KLis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12-each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- memberedheterocycle; and R50is selected from a substituent capable of reacting with a nucleophilic group on a Drug unit.

[0227] In an aspect, the present disclosure provides a Linker of Formula (XXX-I):or a pharmaceutically acceptable salt thereof, wherein; D is selected from a Drug unit; X is selected from CH and N; Y is selected from -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is a peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3-C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, S1, S2, S3, and S4are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl; M1is a group which can react with a ligand to form a connector unit; K1is selected from KBand KL; KBis selected from: (i) a peptide unit, (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; KLis selected from: (i) a peptide unit, (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- memberedheterocycle; and R50is selected from a substituent capable of reacting with a nucleophilic group on a Drug unit.

[0228] In an aspect, the present disclosure provides a Linker of Formula (XXX-II):Formula (XXX-II), or a pharmaceutically acceptable salt thereof, wherein; D is selected from a Drug unit; X is selected from CH and N; Y is selected from -O-T1and -NH-T2; T1is a sugar cleavable unit;S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, S1, S2, S3, and S4are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl; M1is a group which can react with a ligand to form a connector unit; K1is selected from KBand KL; KBis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; KLis selected from: (i) a peptide unit, (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substitutedN(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- memberedheterocycle; and R50is selected from a substituent capable of reacting with a nucleophilic group on a Drug unit.

[0229] In some embodiments, Formula (XXX) or Formula (XXX-I) is represented by the Formula (XXX-I-A)or a pharmaceutically acceptable salt thereof.

[0230] In some embodiments, Formula (XXX), Formula (XXX-I), or (Formula (XXX-II) is represented by the Formula (XXX-III)or a pharmaceutically acceptable salt thereof.

[0231] In some embodiments, Formula (XXX), Formula (XXX-I), (Formula (XXX-I-A), or Formula (X-III) is represented by the Formula (XXX-III-A)Formula (X-III-A), or a pharmaceutically acceptable salt thereof.

[0232] In some embodiments, for a linker of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXXX-III), or Formula (XXXX-III-A), R50is selected from a substituent capable of reacting with a nucleophilic group on a Drug. In some cases, the nucleophilic group on the Drug contains a nitrogen. In some cases, the nucleophilic group on the Drug contains an oxygen.

[0233] In some embodiments, for a linker of Formula (XXX), Formula (XXX-I), Formula (XXX-I-A), Formula (XXX-II), Formula (XXXX-III) or Formula (XXXX-III-A), R50is selectedfrom halogen,some cases, R50is selected from halogen. In some cases, R50is selected from -OH. In some cases, R50is selectedfrom . In some cases, R50 is selected from. In some cases, R50 isselected from.Table A-B. Exemplary Drug LinkersTable A-L. Exemplary Drug LinkersTable B-B. Exemplary Drug LinkersTable B-L. Exemplary Drug LinkersTable AA-B. Exemplary Conjugates

[0234] For the Table AA-B, L is an antibody or antigen-binding portion thereof.In some embodiments, the exemplary conjugates of Table AA-B have a DAR selected from about 1 to about 8. In some cases, the exemplary conjugates of Table AA-B have a DAR selected from about 4 to about 8. In some cases, the exemplary conjugates of Table AA-B have a DAR of about 8. Table AA-L. Exemplary Conjugates

[0235] For the Table AA-L, L is an antibody or antigen-binding portion thereof.In some embodiments, the exemplary conjugates of Table AA-L have a DAR selected from about 1 to about 8. In some cases, the exemplary conjugates of Table AA-L have a DAR selected from about 4 to about 8. In some cases, the exemplary conjugates of Table AA-L have a DAR of about 8.Table BB-B. Exemplary Conjugates

[0236] For the Table BB-B, L is an antibody or antigen-binding portion thereof.In some embodiments, the exemplary conjugates of Table BB-B have a DAR selected from about 1 to about 8. In some cases, the exemplary conjugates of Table BB-B have a DAR selected from about 4 to about 8. In some cases, the exemplary conjugates of Table BB-B have a DAR of about 8. Table BB-L. Exemplary Conjugates

[0237] For the Table BB-L, L is an antibody or antigen-binding portion thereof.In some embodiments, the exemplary conjugates of Table BB-L have a DAR selected from about 1 to about 8. In some cases, the exemplary conjugates of Table BB-L have a DAR selected from about 4 to about 8. In some cases, the exemplary conjugates of Table BB-L have a DAR of about 8.

[0238] Included in the present disclosure are salts, particularly pharmaceutically acceptablesufficiently acidic, a sufficiently basic, or both functional groups, can react with any of a number of inorganic bases, and inorganic and organic acids, to form a salt. Alternatively, compounds that are inherently charged, such as those with a quaternary nitrogen, can form a salt with an appropriate counterion, e.g., a halide such as bromide, chloride, or fluoride, particularly bromide.

[0239] Chemical entities having carbon-carbon double bonds or carbon-nitrogen double bonds may exist in Z- or E- form (or cis- or trans- form). Furthermore, some chemical entities may exist in various tautomeric forms. Unless otherwise specified, compounds described herein are intended to include all Z-, E- and tautomeric forms as well.

[0240] A “tautomer” refers to a molecule wherein a proton shift from one atom of a molecule to another atom of the same molecule is possible. The compounds presented herein, in certain embodiments, exist as tautomers. In circumstances where tautomerization is possible, a chemical equilibrium of the tautomers will exist. The exact ratio of the tautomers depends on several factors, including physical state, temperature, solvent, and pH. Some examples of tautomeric equilibrium include:.

[0241] The compounds disclosed herein, in some embodiments, are used in different enriched isotopic forms, e.g., enriched in the content of2H,3H,11C,13C and / or14C. In one particular embodiment, the compound is deuterated in at least one position. Such deuterated forms can be made by the procedure 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 the metabolicstability and or efficacy, thus increasing the duration of action of drugs.

[0242] Unless otherwise stated, compounds described herein are intended to includeexample, compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by13C- or14C-enriched carbon are within the scope of the present disclosure.

[0243] The compounds of the present disclosure optionally contain unnatural proportions of atomic isotopes at one or more atoms that constitute such compounds. For example, thecompounds may be labeled with isotopes, such as for example , deuterium (2H), tritium (3H),iodine-125 (125I) or carbon-14 (14C). Isotopic substitution with2H,11C,13C,14C,15C,12N,13N,15N,16N,16O,17O,14F,15F,16F,17F,18F,33S,34S,35S,36S,35Cl,37Cl,79Br,81Br, and125I are all contemplated. All isotopic variations of the compounds of the present invention, whetherradioactive or not, are encompassed within the scope of the present invention.

[0244] In certain embodiments, the compounds disclosed herein have some or all of the1H atoms replaced with2H atoms. The methods of synthesis for deuterium-containing compounds are known in the art and include, by way of non-limiting example only, the following synthetic methods.

[0245] Deuterium substituted compounds are synthesized using various methods such as described in: Dean, Dennis C.; Editor. 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.

[0246] Deuterated starting materials are readily available and are subjected to the synthetic methods described herein to provide for the synthesis of deuterium-containing compounds. Large numbers of deuterium-containing reagents and building blocks are available commercially from chemical vendors, such as Aldrich Chemical Co.

[0247] Compounds of the present invention also include crystalline and amorphous forms of those compounds, pharmaceutically acceptable salts, and active metabolites of these compounds having the same type of activity, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, unsolvated polymorphs (including anhydrates), conformational polymorphs,and amorphous forms of the compounds, as well as mixtures thereof.

[0248] The compounds described herein may in some cases exist as diastereomers, enantiomers, or other stereoisomeric forms. Where absolute stereochemistry is not specified, the compounds presented herein include all diastereomeric, enantiomeric, and epimeric forms as well as the appropriate mixtures thereof. Separation of stereoisomers may be performed by chromatography or by forming diastereomers and separating by recrystallization, or“Enantiomers, Racemates and Resolutions”, John Wiley And Sons, Inc., 1981, herein incorporated by reference for this disclosure). Stereoisomers may also be obtained by stereoselective synthesis.

[0249] The methods and compositions described herein include the use of amorphous forms as well as crystalline forms (also known as polymorphs). The compounds described herein may be in the form of pharmaceutically acceptable salts. As well, in some embodiments, active metabolites of these compounds having the same type of activity are included in the scope of the present disclosure. In addition, the compounds described herein can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. The solvated forms of the compounds presented herein are also considered to be disclosed herein.

[0250] In certain embodiments, compounds or salts of the compounds may be prodrugs, e.g., wherein a hydroxyl in the parent compound is presented as an ester or a carbonate, or carboxylic acid present in the parent compound is presented as an ester. The term “prodrug” is intended to encompass compounds which, under physiologic conditions, are converted into pharmaceutical agents of the present disclosure. One method for making a prodrug is to include one or more selected moieties which are hydrolyzed under physiologic conditions to reveal the desired molecule. In other embodiments, the prodrug is converted by an enzymatic activity of the host animal such as specific target cells in the host animal. For example, esters or carbonates (e.g., esters or carbonates of alcohols or carboxylic acids and esters of phosphonic acids) are preferred prodrugs of the present disclosure.

[0251] Prodrug forms of the herein described compounds, wherein the prodrug is metabolized in vivo to produce a compound as set forth herein are included within the scope of the claims. In some cases, some of the herein-described compounds may be a prodrug for another derivative or active compound.

[0252] Prodrugs are often useful because, in some situations, they may be easier to administer than the parent drug. They may, for instance, be bioavailable by oral administration whereas the parent is not. Prodrugs may help enhance the cell permeability of a compound relative to the parent drug. The prodrug may also have improved solubility in pharmaceutical compositions over the parent drug. Prodrugs may be designed as reversible drug derivatives, for use as modifiers to enhance drug transport to site-specific tissues or to increase drug residence inside of a cell.

[0253] In some embodiments, the design of a prodrug increases the lipophilicity of the pharmaceutical agent. In some embodiments, the design of a prodrug increases the effectiveGastroenterol, 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 A.C.S. Symposium Series;and Edward B. Roche, Bioreversible Carriers in Drug Design , American PharmaceuticalAssociation and Pergamon Press, 1987, all incorporated herein for such disclosure). According to another embodiment, the present disclosure provides methods of producing the above-defined compounds. The compounds may be synthesized using conventional techniques. Advantageously, these compounds are conveniently synthesized from readily available starting materials.

[0254] Synthetic chemistry transformations and methodologies useful in synthesizing the compounds described herein are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations (1989); T. W. Greene and P. G. M. 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 (1995). Targeting Unit (L)

[0255] In some embodiments, for a Drug-Linker or salt of Formula (X-I), Formula (X-I-A), Formula (X-I-B), Formula (X-I-Ba), Formula (X-I-Baa), Formula (X-I-C), Formula (X-I-CB), Formula (X-I-D), Formula (X-I-DB), Formula (X-II), Formula (X-II-A), Formula (X-II-B), Formula (X-II-C), Formula (X-II-CB), Formula (X-II-D ), Formula (X-II-DB), Formula (X-III), Formula (X-III-A), Formula (X-III-Aa), Formula (X-III-Aaa), Formula (X-III-C), or Formula (X-III-D) (each of which further comprises a targeting unit), or for a conjugate or salt of Formula (XX), Formula (XX-I), Formula (XX-I-A), Formula (XX-I-B), Formula (XX-I-Aa), Formula (XX-I-Ab), Formula (XX-II), Formula (XX-II-A), Formula (XX-II-B), Formula (XX- III), Formula (XX-III-A), Formula (XX-III-Aa), or Formula (XX-III-Ab), the Targeting Unit (L) is selected from an antibody or an antigen-binding fragment thereof. In some cases, the Targeting Unit is selected from a group consisting of chimeric antibodies, humanized antibodies, and human antibodies. In some cases, the Targeting Unit, performs a targeting function. In some cases, a Targeting unit specifically binds to a target molecule. In some cases, specifically binds refers to the ability of a Targeting unit (e.g., an antibod...

Claims

CLAIMS WHAT IS CLAIMED IS:

1. A Drug-Linker of Formula (X):Formula (X) or a pharmaceutically acceptable salt thereof, wherein;D is selected from a Drug unit; X is selected from CH and N; Y is selected from -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is a peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, ––S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, S1, S2, S3, and S4are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, - OC(O)R30, -S(O)R30, -S(O)2R30, -O-S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl; M1is a group which can react with a ligand to form a connector unit; K1is selected from KBand KL; KBis selected from: (i) a peptide unit, (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O-KLis selected from: (i) a peptide unit, (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- memberedheterocycle.

2. The Drug-Linker or salt of claim 1, wherein Formula (X) or Formula (X-I) is represented by the structure of Formula (X-I-A)Formula (X-I-A), or a pharmaceutically acceptable salt thereof.

3. The Drug-Linker or salt of claims 1 or 2, wherein S1is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, – N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or – P(O)(R20)2–.

4. The Drug-Linker or salt of any one of claims 1 to 3, wherein S1is selected from anare optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, or – C(O)–.

5. The Drug-Linker or salt of any one of claims 1 to 4, wherein S1is a branched alkylene.

6. The Drug-Linker or salt of any one of claims 1 to 5, wherein.

7. The Drug-Linker or salt of any one of claims 1 to 4, wherein S1is selected from an optionally substituted C1-C2alkylene wherein one or more alkylene units of the C1-C2alkylene are optionally and independently replaced by –N(R20)–.

8. The Drug-Linker or salt of any one of claims 1 to 4 or 7, wherein S1is.

9. The Drug-Linker or salt of any one of claims 1 to 8, wherein S2is selected from an optionally substituted C8-C12alkylene wherein one or more alkylene units of the C8-C12alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, –O–, and –C(O)–.

10. The Drug-Linker or salt of any one of claims 1 to 9, wherein S2is a linear alkylene.

11. The Drug-Linker or salt of any one of claims 1 to 10, wherein S2is.

12. The Drug-Linker or salt of any one of claims 1 to 11, wherein S1-S2is selected from.

14. The Drug-Linker or salt of any one of claims 1 to 13, wherein Formula (X) or Formula (X-I-A) is represented by the structure of Formula (X-I-C)Formula (X-I-C),or a pharmaceutically acceptable salt thereof .

15. The Drug-Linker of any one of claims 1 to 14, wherein Y is -NH-T2.

16. The Drug-Linker of any one of claims 1 to 15, wherein the peptide unit of T2includes one or more amino acids selected from a group consisting of 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.

17. The Drug-Linker of any one of claims 1 to 16, wherein the peptide unit of T2includes a dipeptide or tripeptide.

18. The Drug-Linker of any one of claims 1 to 17, wherein the peptide unit of T2has a capping moiety, wherein the capping moiety is.

19. The Drug-Linker of any one of claims 1 to 18, wherein the peptide unit of T2is selected.

20. The Drug-Linker of any one of claims 1 to 19, wherein Y-S4-K1is selected from.

21. The Drug-Linker of any one of claims 1 to 20, wherein S4is.

22. The Drug-Linker of any one of claims 1 to 21, wherein Y-S4-K1is selected from.

23. The Drug-Linker of any one of claims 1 to 21, wherein each KBis selected from a peptide unit.

24. The Drug-Linker of any one of claims 1 to 23, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

25. The Drug-Linker of any one of claims 1 to 24, wherein the peptide unit has a terminus unit represented by R6, wherein R6is selected from -OH, -NH2, and.

26. The Drug-Linker of any one of claims 1 to 25, wherein KBis selected from ,27. The Drug-Linker or salt of any one of claims 1 to 26, wherein Y-S4-K1is selected from,,.

28. The Drug-Linker or salt of any one of claims 1 to 20, wherein S4is.

29. The Drug-Linker or salt of any one of claims 1 to 20 or 28, wherein Y-S4-K1is selected.

30. The Drug-Linker or salt of any one of claims 1 to 20, 28 or 29, wherein KBis selectedfrom31. The Drug-Linker or salt of any one of claims 1 to 20 or 28 to 30, wherein Y-S4-K1is selected from.

33. The Drug-Linker or salt of any one of claims 1 to 19 or 32, wherein S4is absent.

34. The Drug-Linker or salt of claims 1 to 19, 32 or 33, wherein KLis a peptide unit.

35. The Drug-Linker or salt of any one of claims 1 to 19 or 32 to 34, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

36. The Drug-Linker or salt of any one of claims 1 to 19 or 32 to 35, wherein the peptide unit has a capping moiety, wherein the capping moiety is.

37. The Drug-Linker or salt of any one of claims 1 to 19 or 32 to 36, wherein KLis selected.

38. The Drug-Linker or salt of any one of claims 1 to 19 or 32 to 37, wherein Y-S4-K1is ,39. The Drug-Linker or salt of any one of claims 1 to 19 or 32 to 37, wherein Y-S4-K1is.

40. The Drug-Linker or salt of any one of claims 1 to 19 or 32, wherein each S4is.

41. The Drug-Linker or salt of any one of claims 1 to 19, 32, or 40, wherein S4is.

42. The Drug-Linker or salt of any one of claims 1 to 19, 32, 40, or 41, wherein Y-S4-K1is.

43. The Drug-Linker or salt of any one of claims 1 to 19, 32, or 40 to 42, wherein KLis a peptide unit.

44. The Drug-Linker or salt of any one of claims 1 to 19, 32, or 40 to 43, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

45. The Drug-Linker or salt of any one of claims 1 to 19, 32, or 40 to 44, wherein the peptide unit has a terminus unit represented by R6, wherein R6is selected from -OH, and -NH2.

46. The Drug-Linker or salt of any one of claims 1 to 19, 32, or 40 to 45, wherein KLis.

47. The Drug-Linker or salt of any one of claims 1 to 19, 32, or 40 to 46, wherein Y-S4-K1is selected from.

48. The Drug-Linker or salt of any one of claims 1 to 47, wherein X is CH.

49. The Drug-Linker or salt of any one of claims 1 to 47, wherein X is N.

50. The Drug-Linker or salt of any one of claims 1 to 49, wherein the Drug unit is selected from a cytotoxic agent, an immune modulatory agent, a nucleic acid, a growth inhibitory agent, a PROTAC, a toxin, a radioactive isotope and a chelating ligand.

51. The Drug-Linker or salt of any one of claims 1 to 50, wherein the Drug unit is selected from a cytotoxic agent, camptothecin derivative, and an immune modulatory agent.

52. The Drug-Linker or salt of any one of claims 1 to 51, wherein the Drug unit is selected,.

53. The Drug-Linker or salt of any one of claims 1 to 52, wherein the Drug unit is .. r salt of any one of claims 1 to 53, wherein M1is wherein M1isOH, -SH, -NH2, and -ONH2.

55. The Drug-Linker or salt of any one of claims 1 to 54, wherein.

56. A Drug-Linker selected from Table A-B, Table A-L, Table B-B, and Table B-L.

57. A Drug-Linker selected from Table A-B.

58. A Drug-Linker selected from Table A-L.

59. A Drug-Linker selected from Table B-B.

60. A Drug-Linker selected from Table B-L.

61. A conjugate comprising a Drug-Linker or salt of any one of claims 1 to 60, and a Targeting Unit, wherein M1of the Drug-Linker reacts and forms a covalent bond to the Targeting Unit.

62. The conjugate of claim 61, having an average ratio of Drug-Linker to Targeting unit is about 8.

63. A conjugate of the Formula (XX):Formula (XX), or a pharmaceutically acceptable salt thereof, wherein; R40 is selectedD is selected from a Drug unit; X is selected from CH and N; Y is a -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M2, K1, S1, S2, S3, and S4are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl; L is a Targeting Unit; M2is a connector unit; K1is selected from KBand KL; KBis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and(iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; KLis selected from: (i) a peptide unit; (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, -N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12-membered heterocycle.

64. The conjugate or salt of claim 63, wherein Formula (XX) or Formula (XX-I) is represented by the structure of Formula (XX-I-A)Formula (XX-I-A), or a pharmaceutically acceptable salt thereof.

65. The conjugate or salt of claims 63 or 64, wherein S1is selected from an optionallyoptionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, – N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or – P(O)(R20)2–.

66. The conjugate or salt of any one of claims 63 to 65, wherein S1is selected froman optionally substituted C6-C10alkylene wherein one or more alkylene units of the C6-C10alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, or – C(O)–.

67. The conjugate or salt of any one of claims 63 to 66, wherein S1is a branched alkylene.

68. The conjugate or salt of any one of claims 63 to 66, wherein.

69. The conjugate or salt of any one of claims 63 to 68, wherein S1is selected from an optionally substituted C1-C2alkylene wherein one or more alkylene units of the C1-C2alkylene are optionally and independently replaced by –N(R20)–.

70. The conjugate or salt of any one of claims 63 to 66 or 69, wherein S1is.

71. The conjugate or salt of any one of claims 63 to 70, wherein S2is selected from an optionally substituted C8-C12alkylene wherein one or more alkylene units of the C8-C12alkylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, –O–, and –C(O)–.

72. The Drug-Linker or salt of any one of claims 63 to 71, wherein S2is a linear alkylene.

73. The Drug-Linker or salt of any one of claims 63 to 72, wherein S2is.

74. The conjugate or salt of any one of claims 63 to 73, wherein S1-S2is selected from.

75. The conjugate or salt of any one of claims 63 to 74, wherein S3is absent.

76. The conjugate or salt of any one of claims 63 to 75, wherein Formula (XX) or Formula (XX-I-A) is represented by the structure of Formula (XX-I-C)Formula (XX-I-C), or a pharmaceutically acceptable salt thereof.

77. The conjugate of any one of claims 63 to 76, wherein Y is -NH-T2.

78. The conjugate of any one of claims 63 to 77, wherein the peptide unit of T2includes one or more amino acids selected from a group consisting of 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.

79. The conjugate of any one of claims 63 to 78, wherein the peptide unit of T2includes a dipeptide or tripeptide.

80. The conjugate of any one of claims 63 to 79, wherein the peptide unit of T2has a capping81. The conjugate of any one of claims 63 to 80, wherein the peptide unit of T2is selected.

82. The conjugate of any one of claims 63 to 81, wherein Y-S4-K1is selected from.

83. The conjugate of any one of claims 63 to 82, wherein S4is.

84. The conjugate of any one of claims 63 to 83, wherein Y-S4-K1is selected from.

85. The conjugate of any one of claims 63 to 84, wherein each KBis selected from a peptide unit.

86. The conjugate of any one of claims 63 to 85, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

87. The conjugate of any one of claims 63 to 86, wherein the peptide unit has a terminus unit represented by R6, wherein R6is selected from -OH, -NH2, and.

88. The conjugate of any one of claims 63 to 87, wherein KBis selected from ,89. The conjugate or salt of any one of claims 63 to 88, wherein Y-S4-K1is selected from,,.

90. The conjugate or salt of any one of claims 63 to 82, wherein S4is.

91. The conjugate or salt of any one of claims 63 to 82, or 90, wherein Y-S4-K1is selected.

92. The conjugate or salt of any one of claims 63 to 82, or 90 to 91, wherein KBis selected93. The conjugate or salt of any one of claims 63 to 82, or 90 to 92, wherein Y-S4-K1is.

94. The conjugate or salt of any one of claims 63 to 76, wherein Y-S4-K1is selected from.

95. The conjugate or salt of any one of claims 63 to 76 or 94, wherein S4is absent.

96. The conjugate or salt of claims 63 to 76, or 94 to 95, wherein KLis a peptide unit.

97. The conjugate or salt of any one of claims 63 to 76, or 94 to 96, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

98. The conjugate or salt of any one of claims 63 to 76, or 94 to 97, wherein the peptide unit has a capping moiety, wherein the capping moiety is.

99. The conjugate or salt of any one of claims 63 to 76, or 94 to 98, wherein KLis selected.

100. The conjugate or salt of any one of claims 63 to 76, or 94 to 99, wherein Y-S4-K1is ,101. The conjugate or salt of any one of claims 63 to 76, or 94 to 100, wherein Y-S4-K1is.

102. The conjugate or salt of any one of claims 63 to 76, or 94 to 101, wherein each S4is.

103. The conjugate or salt of any one of claims 63 to 76, or 94 to 102, wherein S4is.

104. The conjugate or salt of any one of claims 63 to 76, or 94 to 103, wherein Y-S4-K1is.

105. The conjugate or salt of any one of claims 63 to 76, or 94 to 104, wherein KLis a peptide unit.

106. The conjugate or salt of any one of claims 63 to 76, or 94 to 105, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

107. The conjugate or salt of any one of claims 63 to 76, or 94 to 106, wherein the peptide unit has a terminus unit represented by R6, wherein R6is selected from -OH, and -NH2.

108. The conjugate or salt of any one of claims 63 to 76, or 94 to 107, wherein KLis selected.

109. The conjugate or salt of any one of claims 63 to 76, or 94 to 108, wherein Y-S4-K1is selected from.

110. The conjugate or salt of any one of claims 63 to 76, or 94 to 109, wherein X is CH.

111. The conjugate or salt of any one of claims 63 to 76, or 94 to 109, wherein X is N.

112. The conjugate or salt of any one of claims 63 to 76, or 94 to 110, wherein the Drug unit is selected from a cytotoxic agent, an immune modulatory agent, a nucleic acid, a growthinhibitory agent, a PROTAC, a toxin, a radioactive isotope and a chelating ligand.

113. The conjugate or salt of any one of claims 63 to 76, or 94 to 112, wherein the Drug unit is selected from a cytotoxic agent, camptothecin derivative, and an immune modulatory agent.

114. The conjugate or salt of any one of claims 63 to 76, or 94 to 113, wherein the Drug unit.

115. The conjugate or salt of any one of claims 63 to 76, or 94 to 114, wherein M2is selected116. The conjugate or salt of any one of claims 63 to 115, wherein M2is.

117. The conjugate or salt of any one of claims 63 to 116, wherein the Targeting unit is selected from an antibody or an antigen-binding portion thereof.

118. The conjugate of any one of claims 63 to 117, wherein the Targeting unit is a monoclonal antibody.

119. The conjugate or salt of any one of claims 63 to 118, having an average ratio of Drug- Linker to Targeting unit (DAR) of about 1 to about 10.

120. The conjugate or salt of any one of claims 63 to 119, having an average ratio of Drug- Linker to Targeting unit (DAR) of about 2 to about 8.

121. The conjugate or salt of any one of claims 63 to 120, having an average ratio of Drug- Linker to Targeting unit (DAR) of about 4.

122. The conjugate or salt of any one of claims 63 to 121, having an average ratio of Drug- Linker to Targeting unit (DAR) of about 8.

123. The conjugate of any one of claims 63 to 122, wherein the antibody is an anti-5T4 antibody.

124. The conjugate of claim 123, wherein the anti-5T4 antibody is selected from 5T4-1EL, 5T4-2EL, 5T4-3EL, 5T4-3EL-VL, 5T4-4EL, 5T4-5EL, 5T4-5EL-VH, 5T4-6EL, 5T4-7EL, 5T4- 8EL, 5T4-9, 5T4-9EL, 5T4-10EL, 5T4-11EL, 5T4-12EL, 5T4-13EL, 5T4-14EL, 5T4-15EL, 5T4-16, 5T4-17, 5T4-18, 5T4-19, 5T4-20, and 5T4-21.

125. The conjugate of any one of claims 123 to 124, wherein the anti-5T4 antibody is 5T4- 7EL.

126. A Conjugate selected from Table AA-B, Table AA-L, BB-B, and Table BB-L.

127. A Conjugate selected from Table AA-B.

128. A Conjugate selected from Table AA-L.

129. A Conjugate selected from Table BB-B.

130. A Conjugate selected from Table BB-L.

131. A pharmaceutical composition comprising a conjugate of any one of claims 63 to 130 and a pharmaceutically acceptable excipient.

132. A method of treating a subject with a disease or disorder, comprising administering to the subject in need thereof a therapeutically effective amount of a conjugate of any one of claims 63 to 130 or a pharmaceutical composition of claim 131.

133. The method of claim 132, wherein the disease or disorder is a cancer.

134. A method of treating a subject with a cancer, comprising administering to the subject in need thereof a conjugate of any one of claims 63 to 130 or a pharmaceutical composition of claim 131.

135. A method of treating a subject with a tumor, comprising administering to the subject in need thereof a conjugate of any one of claims 63 to 130 or a pharmaceutical composition of claim 131.

136. The method of claim 135, wherein the tumor is associated with a cancer.

137. Use of a conjugate, for treating a subject with a disease or disorder, comprising administering to the subject in need thereof a conjugate of any one of claims 63 to 130 or a pharmaceutical composition of claim 131.

138. The use of claim 126, wherein the disease or disorder is a cancer.

139. The method of any one of claims 133 to 138, wherein the cancer is selected from: cancers of the head and neck which include tumors of the head, neck, nasal cavity, paranasal sinuses, nasopharynx, oral cavity, oropharynx, larynx, hypopharynx, salivary glands, and paragangliomas; cancers of the liver and biliary tree, particularly hepatocellular carcinoma;lung cancer (SCLC and NSCLC); breast cancer sarcomas, such as fibrosarcoma, malignant fibrous histiocytoma, embryonal rhabdomyosarcoma, leiomysosarcoma, neurofibrosarcoma, osteosarcoma, synovial sarcoma, liposarcoma, and alveolar soft part sarcoma; leukemias such as acute promyelocytic leukemia (APL), acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myelogenous leukemia (CML); neoplasms of the central nervous systems, particularly brain cancer; multiple myeloma (MM), lymphomas such as Hodgkin's lymphoma, lymphoplasmacytoid lymphoma, follicular lymphoma, mucosa-associated lymphoid tissue lymphoma, mantle cell lymphoma, B-lineage large cell lymphoma, Burkitt's lymphoma, and T-cell anaplastic large cell lymphoma.

140. The method of any one of claims 133 to 138, wherein the cancer is selected from melanoma, skin basal cell cancer, glioblastoma, glioma, gliosarcoma, astrocytoma, meningioma, neuroblastoma, adrenocortical cancer, head and neck cancer (e.g., cancer of the head, neck,nasal cavity, paranasal sinuses, nasopharynx, oral cavity, oropharynx, larynx, hypopharynx,and / or salivary glands, and paragangliomas), oral cancer, salivary gland cancer, nasopharyngealcancer, breast cancer (e.g., triple negative breast cancer), lung cancer (e.g., non -small cell lungcancer (NSCLC), small cell lung cancer, or squamous cell lung cancer), esophageal cancer, gastroesophageal junction cancer, gastric cancer, gastrointestinal cancer, primary peritoneal cancer, liver cancer, hepatocellular carcinoma, gallbladder cancer, biliary tract cancer, cholangiocarcinoma, colon cancer, rectal cancer, colorectal carcinoma, ovarian cancer, fallopian tube cancer, bladder cancer, upper urinary tract cancer, urothelial cancer, renal cell carcinoma,kidney cancer, genitourinary cancer, cervical cancer, testicular cancer, prostate cancer,fibrosarcoma, liposarcoma, rhabdomyosarcoma (e.g., embryonal rhabdomyosarcoma), leiomyosarcoma, neurofibrosarcoma, synovial sarcoma, liposarcoma, alveolar soft part sarcoma, osteosarcoma, histiocytoma (e.g., malignant fibrous histiocytoma), pancreatic cancer, endometrial cancer, cancer of the appendix, thyroid cancer, advanced Merkel cell cancer, multiple myeloma, sarcomas, choriocarcinoma, leukemia (e.g., erythroleukemia, acute lymphoblastic leukemia, acute monocytic leukemia, acute promyelocytic leukemia, acute myeloid leukemia, acute myelogenous leukemia, chronic myeloid leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, acute lymphoblastic leukemia, or mast cell leukemia), lymphoma (e.g., small lymphocytic lymphoma, Burkitt’s lymphoma, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, diffuse large B cell lymphoma, lymphoplasmacytoid lymphoma, mucosa-associated lymphoid tissue lymphoma, mantle cell lymphoma, T-cell anaplastic large cell lymphoma, follicular lymphoma, monocytic lymphoma, or HTLV- associated T cell leukemia / lymphoma), and mesothelioma.

141. The method of any one of claims 133 to 138, wherein the cancer is selected from cell lymphoma, non-small cell lung cancer, large-cell lung cancer, breast cancer, and small-cell lung cancer.

142. The method of any one of claims 133 to 138, wherein the cancer is cell lymphoma.

143. The method of any one of claims 133 to 138, wherein the cancer is non-small cell lung cancer.

144. The method of any one of claims 133 to 138, wherein the cancer is large-cell lung cancer.

145. The method of any one of claims 133 to 138, wherein the cancer is breast cancer.

146. The method of any one of claims 133 to 138, wherein the cancer is small-cell lung cancer.

147. A Linker of Formula (XXX):Formula (XXX), or a pharmaceutically acceptable salt thereof, wherein;R40 is selected fromD is selected from a Drug unit; X is selected from CH and N; Y is selected from -O-T1and -NH-T2; T1is a sugar cleavable unit; T2is a peptide cleavable unit; S1is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted aminoacid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S2is selected from: (i) an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; (ii) optionally substituted C3-C30alkenylene, wherein one or more alkenylene units of the C3- C30alkenylene are optionally and independently replaced by –N(R20)–, –N(R20)C(O)–, – C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, –S(O)2–, or –P(O)(R20)2–; (iii) one or more amino acid(s); (iv) one or more N-substituted amino acid(s); (v) optionally substituted polyether; (vi) optionally substituted C3-C10carbocyclene; (vii) optionally substituted 5- to 10-membered heterocyclene; S3is selected from a spacer, wherein the spacer is preferably phenylene, wherein S3is present or absent; S4is absent or selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, – N(R20)C(O)–, –C(O)N(R20)–, –N(R20)S(O)2–, – S(O)2N(R20)–, –O–, –C(O)–, –OC(O)–, – C(O)O–, –S–, –S(O)–, –S(O)2–, 5- to 6-membered heterocyclene, or –P(O)(R20)2–; wherein the optional substituents on M1, K1, S1, S2, S3, and S4are independently selected at each occurrence from: (i) halogen, -OR30, -N(R30)2, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), and -CN; (ii) C1-10alkyl, C2-10alkenyl, C2-10alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, - C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C3-10carbocycle and 3- to 10-membered heterocycle; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, - N(R30)2, -C(O)R30, -C(O)N(R30)2, -N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, - S(O)2R30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, =O, =S, =N(R30), -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl;K1is selected from KBand KL; KBis selected from: (i) a peptide unit, (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; KLis selected from: (i) a peptide unit, (ii) an oligosaccharide; (iii) a polyether; and (iv) -OS(O)2(OR30)2and -OP(O)(OR30)2; C4-10carbocycle and 4- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, -OR30, -SR30, -N(R30)2, -C(O)R30, -C(O)N(R30)2, - N(R30)C(O)R30,-C(O)OR30, -OC(O)R30, -S(O)R30, -S(O)2R30, -O- S(O)2OR30, -P(O)(OR30)2, -OP(O)(OR30)2, -NO2, and -CN; each R20is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- membered heterocycle; and each R30is independently selected from hydrogen; and C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-12carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, - N(C1-6alkyl)2, C1-10alkyl, -C1-10haloalkyl, -O-C1-10alkyl, oxo, C3-12carbocycle, and 3- to 12- memberedheterocycle; and R50is selected from a substituent capable of reacting with a nucleophilic group on a Drug unit148. The Linker or salt of claim 147, wherein Formula (XXX) is represented by the structure of Formula (XXX-I-A)Formula (XXX-I-A), or a pharmaceutically acceptable salt thereof.

149. The linker or salt of claim 147 or 148, wherein R50 is selected from .

150. The linker or salt of claims 147 or 148, wherein R50 is selected from.

151. The linker of salt of claims 147 or 148, wherein the nucleophilic group on the Drug is - NH2.

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