Conjugates of drugs with targeting units

Abstract

Provided herein is a Drug-Linker of Formula (X*): or a pharmaceutically acceptable salt thereof, wherein D is a Drug unit, M1 is a click group and the further variables of Formula (X*) are as defined in the application. Such compounds can be useful for preparation of anti-cancer agents.

Description

CONJUGATES OF DRUGS WITH TARGETING UNITSCROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 700,539 filed on September 27, 2024 and U.S. Provisional Patent Application No. 63 / 881,212 filed on September 12, 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*):or a pharmaceutically acceptable salt thereof, wherein; each D is independently a Drug unit; each Y1is independently absent or independently selected from -O-T1and -NH-T2; each T1is independently a sugar cleavable unit; each T2is independently a peptide cleavable unit; each S1is independently 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, and –P(O)(R20)2–; each S2is independently 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–;S3is 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–; each S4is independently absent or independently 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–; J is 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, S4, and J, 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 click group wherein the click group comprises at least one click handle selected from azidyl, alkynyl, and alkynylene; each K1is independently selected from: (i) a peptide unit, (ii) an oligosaccharide; and (iii) a polyether; each K2is independently selected from KBand KL;each KBis independently 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 KLis independently 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; 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; z is selected from 0 and 1; and each w is independently selected from 0 and 1 and each v is independently selected from 0 and 1, provided that: when at least one w is 1, then each v is 0 and when at least one v is selected 1, then each w is 0.

[0004] In an aspect, the present disclosure provides a conjugate of the Formula (XX*):or a pharmaceutically acceptable salt thereof, wherein; each D is independently a Drug unit; each Y1is independently absent or independently selected from -O-T1and -NH-T2; each T1is independently a sugar cleavable unit; each T2is independently a peptide cleavable unit; L is a Targeting unit; each S1is independently 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–; each S2is independently 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–; S3is 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–; each S4is independently 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, S4, and L, 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; M2is a connector unit formed from a click group; each K1is independently selected from: (i) a peptide unit, (ii) an oligosaccharide; and (iii) a polyether; each K2is independently selected from KBand KL; each KBis independently 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 KLis independently 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; 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; z is selected from 0 and 1; and each w is independently selected from 0 and 1 and each v is independently selected from 0 and 1, provided that: when at least one w is 1, then each v is 0 and when at least one v is selected 1, then each w is 0. INCORPORATION BY REFERENCE

[0005] 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

[0006] 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 be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also “figure” and “FIG.” herein), of which:

[0007] FIG.1 illustrates the stability of different ADCs in human plasma;

[0008] FIG.2 illustrates the median fluorescence intensity (MFI) of different ADCs binding to LCLC103H cells;

[0009] FIG.3 illustrates the percentage of cellular binding of different ADCs;

[0010] FIG.4 illustrates internalization of different ADCs;

[0011] FIG.5 illustrates the cytotoxicity of various ADCs in Jeko cells;

[0012] FIG.6 illustrates the cytotoxicity of various ADCs in LCLC103H cells;

[0013] FIG.7 illustrates the cytotoxicity of various ADCs in LCLC103H spheroids;

[0014] FIG.8 illustrates the cytotoxicity of various ADCs in PA-1 spheroids;

[0015] FIG.9 illustrates the antitumor activity of various ADCs;

[0016] FIG.10 illustrates the antitumor activity of various ADCs;

[0017] FIG.11 illustrates the log scores of various drug-linkers; and

[0018] FIG.12 illustrates the RP-HPLC-MS; and

[0019] FIG.13 illustrates the HIC. DETAILED DESCRIPTION OF THE INVENTION

[0020] The following description sets forth numerous exemplary configurations, methods, parameters, and the like. It should be recognized, however, that such description is not intended as a limitation on the scope of the present disclosure, but is instead provided as a desc ription of exemplary embodiments.

[0021] 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

[0022] 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.

[0023] “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 otherembodiments, 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-methylethyl (iso-propyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl), 1,1-dimethylethyl (tert-butyl), 1-pentyl (n-pentyl). The alkyl is attached to the rest of the molecule by a single bond.

[0024] The term “Cx-y” or “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 term “C1-6alkyl” 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 term –Cx-yalkylene- refers to a substituted or unsubstituted alkylene chain with from x to y carbons in the alkylene chain. For example –C1-6alkylene- may be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, any one of which is optionally substituted.

[0025] “Alkoxy” refers to a radical bonded through an oxygen atom of the formula –O- alkyl, where alkyl is an alkyl chain as defined above.

[0026] “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 alkenyl is 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.

[0027] “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.

[0028] The terms “Cx-yalkenyl” and “Cx-yalkynyl” refer to substituted or unsubstituted unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, 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, propenylene, butenylene, pentenylene, and hexenylene, any one of which is optionally 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 , andhexynylene, any one of which is optionally substituted. An alkynylene chain may have onetriple bond or more than one triple bond in the alkynylene chain.

[0029] “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 atoms,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).

[0030] “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 tofive 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 comprises two to three carbon atoms (i.e., C2-C3alkenylene). In other embodiments, an alkenylene comprises 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).

[0031] “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 thealkynylene chain to the rest of the molecule and to the radical group may be through an y twocarbons 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).

[0032] “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.

[0033] “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.

[0034] “Aralkenyl” refers to a radical of the formula –Rd-aryl where Rdis an alkenylene chain as defined above. “Aralkynyl” refers to a radical of the formula -Re-aryl, where Reis an alkynylene chain as defined above.

[0035] “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.

[0036] “Carbocyclene” refers to a divalent carbocycle linking the rest of the molecule to a radical group.

[0037] 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.

[0038] “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, norbornyl (i.e., bicyclo[2.2.1]heptanyl), norbornenyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like.

[0039] “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.

[0040] “Cycloalkylalkyl” refers to a radical of the formula –Rc-cycloalkyl where Rcis an alkylene chain as described above.

[0041] “Cycloalkylalkoxy” refers to a radical bonded through an oxygen atom of the formula –O-Rc-cycloalkyl where Rcis an alkylene chain as described above.

[0042] “Halo” or “halogen” refers to halogen substituents such as bromo, chloro, fluoro and iodo substituents.

[0043] 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.

[0044] “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.

[0045] “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.

[0046] “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.

[0047] “Activated group” refers to a cyclic alkyne which is highly reactive due to ring strain towards azide group to form a triazole.

[0048] “Activated disulfide group” refers to a disulfide which is capable to react with a thiol to form a new disulfide bond.

[0049] “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.

[0050] “Heterocycle” refers to a saturated or unsaturated or aromatic ring comprising one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycles include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. Each ring 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.

[0051] “Heterocyclene” refers to a divalent heterocycle linking the rest of the molecule to a radical group.

[0052] “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 maybe 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.

[0053] 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.

[0054] 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.

[0055] 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.

[0056] 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 a direct bond or a straight or branched alkylene, alkenylene, or alkynylene chain, and each Rcis a straight or branched alkylene, alkenylene or alkynylene chain.

[0057] As used in the specification and claims, the singular form “a”, “an” and “the” includes plural references unless the context clearly dictates otherwise.

[0058] 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 fromwhich 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, / ?-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.

[0059] 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, intracap sular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion.

[0060] 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.

[0061] The phrase “pharmaceutically acceptable excipient” or “pharmaceutically acceptable carrier” 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; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) 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 soybeanoil; (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.

[0062] 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.

[0063] 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.

[0064] 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 be used to bring the drug to the target cell population that binds to the ligand, including but not limited 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.

[0065] 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 may be a biological receptor or other structure of a cell such as a tumor antigen.

[0066] 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 protein comprising at least two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds. Each heavy chain comprises a heavy chain variable region (VH) and a heavy chain constant region comprising three domains, CHI, CH2 and CH3. Each light chain comprises a light chain variable region (VL or Vk) and a light chain constant region comprising one singledomain, 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 (HCDR herein designates a CDR from the heavy chain; and LCDR herein designates a CDR from the light chain) 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.

[0067] 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.

[0068] CDR Definitions from www.bioinf.org.uk / abs / info.html#cdrdef (Kabat numbering system for all, except Contact, which uses Chothia numbering system)

[0069] An antibody is said to “specifically bind” to an antigen X if the antibody binds to antigen X with a KD of 5×10−8M or less, more preferably 1×10−8M or less, more preferably 6×10−9M or less, more preferably 3×10−9M or less, even more preferably 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 enhanceor reduce inter-actions with effector cells or the complement system, or to modulate some otherproperty. 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.

[0070] 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 CHI 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, 6thEd., Saunders Elsevier 2007); (iv) a Fd fragment consisting of the VH and CHI 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.

[0071] 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 than antigen 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 certain embodiments, an isolated antibody specifically binds to human antigen X and does not crossreact with other (non-human) antigen X antigens. Moreover, an isolated antibody may be substantially free of other cellular material and / or chemicals.

[0072] 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.

[0073] The term “antibody-drug conjugate,” “conjugate”, or “ADC,” or “immunoconjugate” refers to an antibody or an antigen -binding portion thereof that is covalently or non-covalently bonded, with or without a linker, to one or more biologically active molecule(s).

[0074] 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.

[0075] The term “human monoclonal antibody” means an antibody displaying a single 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 human heavy chain transgene and a light chain transgene fused to an immortalized cell.

[0076] 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.

[0077] 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, but does not have substantially altered biologic activity from the reference antibody or antigenbinding portion. For example, the variant antibody or antigen -binding portion may retain atleast 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.

[0078] 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.

[0079] The term “about” when used in connection with percentages can mean + / -1%.

[0080] 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. Linkers, Drug-Linkers and Conjugates of the Disclosure

[0081] In an aspect, the present disclosure provides a conjugate of Formula (XXX*):or a pharmaceutically acceptable salt thereof, wherein; p is selected from 1 to 20; each D is independently a Drug unit; each Y1is independently absent or independently selected from -O-T1and -NH-T2; each T1is independently a sugar cleavable unit; each T2is independently a peptide cleavable unit; L is a Targeting unit; A1is a Scaffold unit; each S1is independently 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–; each S2is independently 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–; S3is 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–; each S4is independently absent or independently 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, S4, and L, 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; M2is a connector unit formed from a click group; each K1is independently selected from: (i) a peptide unit, (ii) an oligosaccharide; and (iii) a polyether;each K2is independently selected from KBand KL; each KBis independently 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 KLis independently 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; 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; z is selected from 0 and 1; and each w is independently selected from 0 and 1 and each v is independently selected from 0 and 1, provided that: when at least one w is 1, then each v is 0 and when at least one v is selected 1, then each w is 0.

[0082] In some embodiments, for a conjugate or salt of Formula (XXX*), A1is a Scaffold unit. In some cases, the Scaffold unit may be one selected from PCT / EP2022 / 071003. In some cases, the Scaffold unit may be one as described in Chem. Sci., 2022,13, 8781-8790 (David R. Spring et al). In some cases, the precursor to A1is prepared as similarly described in PCT / EP2022 / 071003 and Chem. Sci., 2022,13, 8781-8790 (David R. Spring et al). In some cases, A1includes a portion that has undergone a click reaction.

[0083] In some embodiments, for a conjugate or salt of Formula (XXX*), A1is, wherein t represents the connection to the linker and 1, 2, 3, and 4, represent the connection to L; and q is an integer selected from 1 to 8. In some cases, A1is.

[0084] In some embodiments, for a conjugate or salt of Formula (XXX*), A1is, wherein t represents a connection to the linker and 1, 2, 3, 4, 5, 6, 7, and 8, represent a connection to L; q is an integer selected from 1 to 8. In some cases, q is 2. In some cases, q is 3. In some cases, q is 4. In some cases, A1is, wherein t represents a connection to the linker and 1, 2, 3, 4, 5, 6, 7, and 8, represent a connection to L. In some cases, A1is, wherein trepresents a connection to the linker and 1, 2, 3, 4, 5, 6, 7, and 8, represent a connection to L.

[0085] In some embodiments, for a conjugate or salt of Formula (XXX*), A1is, wherein t represents the connection to the linker and 1, 2, 3, and 4, represent the connection to L; and q is an integer selected from 1 to 8. In some cases, A1is In some cases, A1iswherein t represents a connection to the linker and 1, 2, 3, 4, 5, 6, 7, and 8, represent a connection to L; q is an integer selected from 1 to 8. In some cases, q is 2. In some cases, q is 3. In some cases, q is 4. In some cases, A1is, wherein t represents a connection to the linker and 1, 2, 3, 4, 5, 6, 7, and 8, represent a connection to L. In some cases, A1is, wherein t represents a connection to the linker and 1, 2, 3, 4, 5, 6, 7, and 8, represent a connection to L. In some cases, each K1is independently selected from. In some cases, each Y1is

[0086] In an aspect, the present disclosure provides a Drug-Linker of Formula (X*):or a pharmaceutically acceptable salt thereof, wherein; each D is independently a Drug unit; each Y1is independently absent or independently selected from -O-T1and -NH-T2; each T1is independently a sugar cleavable unit; each T2is independently a peptide cleavable unit; each S1is independently 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, and –P(O)(R20)2–; each S2is independently 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–; S3is 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–; each S4is independently absent or independently 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–; J is 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, S4, and J, 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 click group wherein the click group comprises at least one click handle selected from azidyl, alkynyl, and alkynylene; each K1is independently selected from: (i) a peptide unit, (ii) an oligosaccharide; and (iii) a polyether; each K2is independently selected from KBand KL; each KBis independently 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 KLis independently 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 independentlyselected 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; 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; z is selected from 0 and 1; and each w is independently selected from 0 and 1 and each v is independently selected from 0 and 1, provided that: when at least one w is 1, then each v is 0 and when at least one v is selected 1, then each w is 0.

[0087] In some embodiments, the Drug-Linker of Formula (X*) further comprises a Targeting unit, wherein M1reacts with the Targeting unit (L) and forms M2.

[0088] In some embodiments, Formula (X*) is represented by the structure of Formula (X):or a pharmaceutically acceptable salt thereof, wherein; each D is independently a Drug unit; each Y1is independently absent or independently selected from -O-T1and -NH-T2; each T1is independently a sugar cleavable unit; each T2is independently a peptide cleavable unit; each S1is independently 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, and –P(O)(R20)2–; each S2is independently 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–; S3is 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–; J is 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 J, 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 click group wherein the click group comprises at least one click handle selected from azidyl, alkynyl, and alkynylene; each K1is independently selected from: (i) a peptide unit, (ii) an oligosaccharide; and (iii) a polyether;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; 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; z is selected from 0 and 1; and each w is independently selected from 0 and 1.

[0089] In some embodiments, Formula (X*) is represented by the structure of Formula (XT):or a pharmaceutically acceptable salt thereof, wherein; each D is independently a Drug unit; each Y1is independently absent or independently selected from -O-T1and -NH-T2; each T1is independently a sugar cleavable unit; each T2is independently a peptide cleavable unit; each S1is independently 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, and –P(O)(R20)2–; S3is 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–; each S4is independently absent or independently selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally andindependently 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–; J is 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, S4, and J, 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 click group wherein the click group comprises at least one click handle selected from azidyl, alkynyl, and alkynylene; each K2is independently selected from KBand KL; each KBis independently 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 KLis independently 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; 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; z is selected from 0 and 1; and each v is independently selected from 0 to 1.

[0090] In some embodiments, Formula (X*) or Formula (X) is represented by the structure of Formula (X-D):or a pharmaceutically acceptable salt thereof.

[0091] In some embodiments, Formula (X*), Formula (X), or Formula (X-D) is represented by the structure of Formula (X-D-I):or a pharmaceutically acceptable salt thereof.

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

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

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

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

[0096] In some embodiments, Formula (X*) or Formula (XT) is represented by the structure of Formula (XT-D):or a pharmaceutically acceptable salt thereof.

[0097] In some embodiments, Formula (X*), Formula (XT), or Formula (XT-D) is represented by the structure of Formula (XT-D-I):or a pharmaceutically acceptable salt thereof.

[0098] In some embodiments, Formula (X*), Formula (XT), Formula (XT-D), or Formula (XT-D-I) is represented by the structure of Formula (XT-D-II):or a pharmaceutically acceptable salt thereof.

[0099] In some embodiments, Formula (X*) or Formula (XT) is represented by the structure of Formula (XT-M):or a pharmaceutically acceptable salt thereof.

[0100] In some embodiments, Formula (X*), Formula (XT), or Formula (XT-M) is represented by the structure of Formula (XT-M-I):or a pharmaceutically acceptable salt thereof.

[0101] In some embodiments, Formula (X*), Formula (XT), Formula (XT-M), or Formula (XT-M-I) is represented by the structure of Formula (XT-M-II):or a pharmaceutically acceptable salt thereof.

[0102] In an aspect, the present disclosure provides a conjugate of the Formula (XX*):or a pharmaceutically acceptable salt thereof, wherein; each D is independently a Drug unit; each Y1is independently absent or independently selected from -O-T1and -NH-T2; each T1is independently a sugar cleavable unit; each T2is independently a peptide cleavable unit; L is a Targeting unit; each S1is independently 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–;each S2is independently 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–; S3is 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–; each S4is independently absent or independently 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, S4, and L, 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; M2is a connector unit formed from a click group; each K1is independently selected from: (i) a peptide unit, (ii) an oligosaccharide; and (iii) a polyether; each of which is optionally substituted; each K2is independently selected from KBand KL; each KBis independently 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 KLis independently 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; 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; z is selected from 0 and 1; and each w is independently selected from 0 and 1 and each v is independently selected from 0 and 1, provided that: when at least one w is 1, then each v is 0 and when at least one v is selected 1, then each w is 0.

[0103] In some embodiments, Formula (XX*) is represented by the structure of Formula (XX):or a pharmaceutically acceptable salt thereof, wherein; each D is independently a Drug unit; each Y1is independently absent or independently selected from -O-T1and -NH-T2; each T1is independently a sugar cleavable unit; each T2is independently a peptide cleavable unit; L is a Targeting unit; each S1is independently 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–; each S2is independently 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–; S3is 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 L, 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; M2is a connector unit formed from a click group; each K1is independently selected from: (i) a peptide unit, (ii) an oligosaccharide; and (iii) a polyether; 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; 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; z is selected from 0 and 1; and each w is independently selected from 0 to 1.

[0104] In some embodiments, Formula (XX*) is represented by the structure of Formula (XXT):or a pharmaceutically acceptable salt thereof, wherein; each D is independently a Drug unit; each Y1is independently absent or independently selected from -O-T1and -NH-T2; each T1is independently a sugar cleavable unit;each T2is independently a peptide cleavable unit; L is a Targeting unit; each S1is independently 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–; S3is 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–; each S4is independently absent or independently 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, S4and L, 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; M2is a connector unit formed from a click group; each K2is independently selected from KBand KL; each KBis independently 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 KLis independently 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; 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; z is selected from 0 and 1; and each v is independently selected from 0 to 1.

[0105] In some embodiments, Formula (XX*) or Formula (XX) is represented by the structure of Formula (XX-D):or a pharmaceutically acceptable salt thereof.

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

[0107] In some embodiments, Formula (XX*), Formula (XX), Formula (XX-D), or Formula (XX-D-I) is represented by the structure of Formula (XX-D-II):or a pharmaceutically acceptable salt thereof.

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

[0109] In some embodiments, Formula (XX*), Formula (XX), or Formula (XX-M) is represented by the structure of Formula (XX-M-I):or a pharmaceutically acceptable salt thereof.

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

[0111] In some embodiments, Formula (XX*) or Formula (XXT) is represented by the structure of Formula (XXT-D):or a pharmaceutically acceptable salt thereof.

[0112] In some embodiments, Formula (XX*), Formula (XXT), or Formula (XXT-D) is represented by the structure of Formula (XX-D-I):or a pharmaceutically acceptable salt thereof.

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

[0114] In some embodiments, Formula (XX*) or Formula (XXT) is represented by the structure of Formula (XXT-M):or a pharmaceutically acceptable salt thereof.

[0115] In some embodiments, Formula (XX*), Formula (XXT), or Formula (XXT-M) is represented by the structure of Formula (XXT-M-I):or a pharmaceutically acceptable salt thereof.

[0116] In some embodiments, Formula (XX*), Formula (XXT), Formula (XXT-M), or Formula (XXT-M-I) is represented by the structure of Formula (XXT-M-II):or a pharmaceutically acceptable salt thereof.

[0117] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), or Formula (X-D-II),each S1-S2-K1is independently selected fromeach S2is independently selected from); S3is selected fromJ is selected fromeach Y1is independently absent or selected from a cleavable sugar and cleavable peptide (e.g., dipeptide); M1is selected fromeach K1is independently selected from a peptide unit and an oligosaccharide; andeach D is independently selected from,.

[0118] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), or Formula (X-D-II),each S1-S2-K1 is independently selected fromeach S2is independently selected from(preferablyS3isJ iseach Y1is independently selected fromM1is selected fromeach K1is independently selected from a peptide unit and an oligosaccharide; and each D is independently selected from,.

[0119] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), or Formula (X-D-II),each S1-S2-K1is independently selected fromJ-S3iseach Y1is independently selected fromM1is selected fromeach K1is independently selected from; andeach D is independently selected from,.

[0120] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), or Formula (X-D-II), each S1-S2-K1is independently selected fromJ-S3iseach Y1is independently selected fromM1iseach K1is independently selected from,each D is independently selected from

[0121] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), S1-S2-K1is selected fromS2is selected from(preferably);S3 is selected fromJ is selected fromY1is absent or selected from a cleavable sugar and cleavable peptide (e.g., dipeptide); M1is selected fromK1is selected from a peptide unit and an oligosaccharide; and D is selected from

[0122] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), S1-S2-K1is selected fromS2is selected from(preferably); S3isJ isY1is selected fromM1is selected fromK1is selected from a peptide unit and an oligosaccharide; and D is selected from

[0123] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), S1-S2-K1is selected fromJ-S3isY1is selected fromM1is selected fromK1is selected fromD is selected from

[0124] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), S1-S2-K1is selected fromJ-S3isY1is selected fromM1isK1is selected from; and D is selected from

[0125] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), or Formula (XT-D-II), each Y1-S4-K2is independently 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;each S4is independently absent or independently selected fromandS3is selected fromJ is selected fromM1is selected fromeach K2is independently selected from KBand KL; each KBis independently 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; each KLis independently 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; andeach D is independently selected from,.

[0126] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), or Formula (XT-D-II), each Y1-S4-K2is independently selected fromeach S4is independently absent or independently selected fromandS3isJ isM1is selected fromeach KBis independently 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; each KLis independently 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; and each D is independently selected from,.

[0127] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), or Formula (XT-D-II),each Y1-S4-K2is independently selected from,J-S3isM1is selected fromeach KBand each KLare independently selected from ,,each D is independently selected from.

[0128] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), or Formula (XT-D-II), each Y1-S4-K2is independently selected fromJ-S3isM1iseach KBis independently selected fromeach KLis independently selected fromeach D is independently selected from

[0129] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-M), Formula (XT-M-I), or Formula (XT-M-II), Y1-S4-K2is 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; S4is absent or selected fromS3is selected fromJ is selected fromM1is selected fromK2is 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; andD is selected from

[0130] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-M), Formula (XT-M-I), or Formula (XT-M-II), Y1-S4-K2is selected fromS4is absent or selected fromS3isJ isM1is selected fromKBis 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; and D is selected from

[0131] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-M), Formula (XT-M-I), or Formula (XT-M-II), Y1-S4-K2is selected fromJ-S3isM1is selected fromKBand KLare selected fromD is selected from

[0132] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-M), Formula (XT-M-I), or Formula (XT-M-II), Y1-S4-K2is selected fromJ-S3is M1isKBis selected fromKLis selected fromD is selected from

[0133] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each K1is independently a hydrophilic spacer. In some cases, each K1is independently selected from polyethylene glycol units, cyclodextrin units, polyamides, hydrophilic peptides, polysaccharides and dendrimers. In some cases, each K1is independently selected from polyamides, hydrophilic peptides, and polysaccharides. In some cases, each K1is independently selected from hydrophilic peptides and polysaccharides. In some cases, each K1is independently selected from hydrophilic peptides. In some cases, each K1is independently selected from polysaccharides.

[0134] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), K1is a hydrophilic spacer. In some cases, K1is selected from polyethylene glycol units, cyclodextrin units, polyamides, hydrophilic peptides, polysaccharides and dendrimers. In some cases, K1is selected from polyamides, hydrophilic peptides, and polysaccharides. In some cases, K1is selected from hydrophilic peptides and polysaccharides. Insome cases, K1is selected from hydrophilic peptides. In some cases, K1is selected from polysaccharides.

[0135] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each S1is independently 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, each S1is independently 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, each S1is independently an optionally substituted C1alkylene. In some cases, each S1is independently an optionally substituted C2alkylene. In some cases, each S1is independently an optionally substituted C3alkylene. In some cases, each S1is independently an optionally substituted C4alkylene. In some cases, each S1is independently an optionally substituted C5alkylene. In some cases, each S1is independently an optionally substituted C6alkylene. In some cases, each S1is independently an optionally substituted C7alkylene. In some cases, each S1is independently an optionally substituted C8alkylene. In some cases, each S1is independently an optionally substituted C9alkylene. In some cases, each S1is independently an optionally substituted C10alkylene. In some cases, each S1is independently an optionally substituted C11alkylene. In some cases, each S1is independently an optionally substituted C12alkylene. In some cases, each S1is independently an optionally substituted C13alkylene. In some cases, each S1is independently an optionally substituted C14alkylene. In some cases, each S1is independently an optionally substituted C15alkylene. In some cases, each S1is independently an optionally substituted C16alkylene. In some cases, each S1is independently an optionally substituted C17alkylene. In some cases, each S1is independently an optionally substituted C18alkylene. In some cases, each S1is independently an optionally substituted C19alkylene. In some cases, each S1is independently an optionally substituted C20alkylene. In some cases, the one or more alkylene units of the alkylene of each 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 each 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 eachS1are optionally and independently replaced by –N(R20)–. In some cases, the one or more alkylene units of the alkylene of each S1are optionally and independently replaced by – N(R20)C(O)–. In some cases, the one or more alkylene units of the alkylene of each S1are optionally and independently replaced by –C(O)N(R20)–. In some cases, the one or more alkylene units of the alkylene of each S1are optionally and independently replaced by –C(O)–. In some cases, the one or more alkylene units of the alkylene of each S1are optionally and independently replaced by –O–. In some cases, if an alkylene unit of the alkylene is replaced, each alkylene may independently be referred to as a resulting alkylene. In some cases, if two or more of the alkylene units of each S1are independently replaced, the replaced alkylene units are not adjacent alkylene units. In some cases, if two or more of the alkylene units of each S1are independently replaced, the adjacent alkylene units of the resulting alkylene are not replaced. In some cases, if two or more of the alkylene units of each S1are independently replaced, the resulting alkylene has no repeating heteroatoms of adjacent alkylene units. In some cases, if two or more of the alkylene units of each S1are independently 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 each S1are independently replaced, the resulting alkylene unit has no -N- N- or -O-O-. In some cases, if two or more of the alkylene units of each S1are independently replaced, the resulting alkylene unit is a stable alkylene. In some cases, if two or more of the alkylene units of each S1are independently replaced, the resulting alkylene unit is an unreactive alkylene. In some cases, each resulting alkylene independently has only 1 heteroatom. In some cases, each resulting alkylene independently has only 2 heteroatoms, wherein the 2 heteroatoms are different from each other. In some cases, each resulting alkylene independently has only 2 heteroatoms, wherein the 2 heteroatoms are not adjacent to each other. In some cases, each resulting alkylene independently has only 3 heteroatoms, wherein the 3 heteroatoms are not adjacent to each other. In some cases, each alkylene independently has 0 replaced units. In some cases, each alkylene independently has 1 replaced unit. In some cases, each alkylene independently has 2 replaced units. In some cases, each alkylene independently has 3 replaced units. In some cases, each alkylene independently has 4 replaced units. In some cases, each alkylene independently has 5 replaced units. In some cases, each alkylene independently has 6 replaced units. In some cases, no adjacent alkylene units of each alkylene are independently replaced. In some cases, no adjacent alkylene units resulting in two or more adjacent heteroatoms are independently present in each 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 independently present in each resulting alkylene if they come from a singular replaced alkylene unit. In some cases, two heteroatoms can be independently present ineach resulting alkylene if they come from a singular replaced alkylene unit. In some cases, each resulting alkylene independently has two heteroatoms, the two heteroatoms are from a singular replaced alkylene unit. In some cases, there are two heteroatoms independently in each resulting alkylene if they result from a singular replacement of an alkylene unit.

[0136] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D- I), Formula (XX-D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), 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. In some cases, S1is 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, 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 some cases, S1is an optionally substituted C9alkylene. In some cases, S1is an optionally substituted C10alkylene. 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 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 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.

[0137] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each S1is independently selected from: –N(R20)C(O)–C1-C3alkylene– N(R20)C(O)–C1-C3alkylene–N(R20)C(O)–C1-C3alkylene. In some cases, each S1is independently selected from: –NHC(O)–C1-C3alkylene–NHC(O)–C1-C3alkylene–NHC(O)–C1- C3alkylene.

[0138] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), S1is selected from: –N(R20)C(O)–C1-C3alkylene–N(R20)C(O)–C1-C3alkylene–N(R20)C(O)–C1-C3alkylene. In some cases, S1is selected from: –NHC(O)–C1-C3alkylene–NHC(O)–C1-C3alkylene–NHC(O)–C1-C3alkylene.

[0139] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), the optional substituents on each 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 each 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 each S1are independently selected at each occurrence from: halogen, - OR30, -N(R30)2, =O, and -CN. In some cases, the optional substituents on each S1are independently selected at each occurrence from halogen, -CN, and =O. In some cases, the optional substituents on each S1are independently selected at each occurrence from F and =O. In some cases, the optional substituents on each S1are independently selected at each occurrence from =O. In some cases, the S1is unsubstituted.

[0140] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), 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 halogen, -CN, and =O. In some cases, the optional substituents on S1are independently selected at each occurrence from F and =O. In some cases, the optionalsubstituents on S1are independently selected at each occurrence from =O. In some cases, the S1is unsubstituted.

[0141] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), the optionally substituted C1-C30alkylene of each S1is independently selected from a branched alkylene or a linear alkylene. In some cases, the optionally substituted C1-C30alkylene of each S1is independently a linear alkylene. In some cases, the optionally substituted C1-C30alkylene of each S1is independently a branched alkylene. In some cases, the optionally substituted C1-C25alkylene of each S1is independently a linear alkylene. In some cases, the optionally substituted C1-C25alkylene of each S1is independently a branched alkylene. In some cases, the optionally substituted C1-C20alkylene of each S1is independently a linear alkylene. In some cases, the optionally substituted C1-C20alkylene of each S1is independently a branched alkylene.

[0142] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), the optionally substituted C1-C30alkylene of S1is independently selected from a branched alkylene or a linear alkylene. In some cases, the optionally substituted C1-C30alkylene of S1is a linear alkylene. In some cases, the optionally substituted C1-C30alkylene of S1is a branched alkylene. In some cases, the optionally substituted C1-C25alkylene of S1is a linear alkylene. In some cases, the optionally substituted C1-C25alkylene of S1is a branched alkylene. In some cases, the optionally substituted C1-C20alkylene of S1is a linear alkylene. In some cases, the optionally substituted C1-C20alkylene of S1is a branched alkylene.

[0143] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II),Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each S1is independently selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(H)C(O)–. In some cases, each S1is independently selected from an optionally substituted C1-C25alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(H)C(O)–. In some cases, each S1is independently selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C20alkylene are optionally and independently replaced by –N(H)C(O)–.

[0144] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), 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(H)C(O)–. In some cases, S1is selected from an optionally substituted C1-C25alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by – N(H)C(O)–. In some cases, S1is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C20alkylene are optionally and independently replaced by – N(H)C(O)–.

[0145] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each S1is independently selected from -NH-C(O)-C1-C6alkylene-NH- C(O)-C1-C6alkylene-NH-C(O)-C1-C6alkylene-. In some cases, each S1is independently selected from -NH-C(O)-C1-C4alkylene-NH-C(O)-C1-C4alkylene-NH-C(O)-C1-C4alkylene-. In somecases, each S1is independently selected from -NH-C(O)-C1-C4alkylene-NH-C(O)-C1-C4alkylene-NH-C(O)-C1alkylene-. In some cases, each S1is independently selected from -NH- C(O)-C1-C4alkylene-NH-C(O)-C1-C4alkylene-NH-C(O)-.

[0146] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each S1is independently selected from -NH-C(O)-C1-C6alkylene-NH-C(O)-C1-C6alkylene-NH-C(O)-C1-C6alkylene-, wherein each -S2-K1is independently bound to one of the alkylene units. In some cases, each S1is independently selected from, wherein each -S2-K1is independently bound to one of the alkylene units. In some cases, each S1is independently selected from, wherein each -S2-K1is independently bound to one of the alkylene units, and wherein S2is -C(O)-.

[0147] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), S1is selected from -NH- C(O)-C1-C6alkylene-NH-C(O)-C1-C6alkylene-NH-C(O)-C1-C6alkylene-, wherein each -S2-K1is independently bound to one of the alkylene units. In some cases, S1is selected from, wherein each -S2-K1is independently bound to one of the alkylene units. In some cases, S1is independently selected from, wherein each -S2-K1is independently bound to one of the alkylene units, and wherein S2is -C(O)-.

[0148] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each S1is independently selected from -NH- C(O)-C1-C6alkylene-NH-C(O)-C1-C6alkylene-NH-C(O)-C1-C6alkylene-. In some cases, each S1is independently selected fromIn some cases, each S1is

[0149] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), S1is selected from -NH-C(O)-C1-C6alkylene- NH-C(O)-C1-C6alkylene-NH-C(O)-C1-C6alkylene-. In some cases, each S1is independently selected from. In some cases, S1selected from

[0150] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each S1-S2-K1is independently selected fromIn some cases, each S1-S2-K1is

[0151] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), -S1-S2-K1is selected from 12 1In some cases, S -S -K is selected from

[0152] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each S1-S2-K1is independently represented byIn some cases, eachis independently selectedfromwhereinis bound to one of the alkylene units. In some cases, eachis independently selected from, whereinis bound to one of the alkylene units. In some cases, eachindependently selected from independently selected from independently selected from independently selected from independently selected from independently selected from

[0153] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), S1-S2-K1is represented byIn some cases,is selected fromwhereinis bound to one of the alkylene units. In some cases,is selected fromwhereinis bound to one of the alkylene units. In some cases,is selected fromIn some cases,

[0154] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each S2is independently 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, each S2is independently 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, each S2is independently 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, each S2is independently 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, each S2is independently 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, each S2is independently selected from an optionally substituted C1-C30alkylenewherein 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, each S2is independently 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, each S2is independently 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, each S2is independently 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, each S2is independently 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, each S2is independently 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, each S2is independently 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, each S2is independently 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, each S2is

[0155] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), 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)–, or –S(O)2–. 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)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, S2is 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, S2is selected from an optionallysubstituted 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, S2is 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, S2is 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, S2is 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, S2is 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, S2is 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, S2is 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, S2is 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, S2is 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, S2is 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, S2is.

[0156] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each S2is independently 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, each S2is independently 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, each S2is independentlyselected from –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, and –C(O)–. In some cases, each S2is independently selected from –NH–, –NHC(O)–, –C(O)NH–, and –C(O)–. In some cases, each S2is independently selected from –NHC(O)–, –C(O)NH–, and –C(O)–. In some cases, each S2is – C(O)–. In some cases, each S2is independently selected from –N(R20)C(O)– and –C(O)N(R20)–. In some cases, each S2is independently selected from –N(R20)–.

[0157] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), S2is 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, S2is 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, S2is selected from –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, and – C(O)–. In some cases, S2is selected from –NH–, –NHC(O)–, –C(O)NH–, and –C(O)–. In some cases, S2is selected from –NHC(O)–, –C(O)NH–, and –C(O)–. In some cases, S2is –C(O)–. In some cases, S2is selected from –N(R20)C(O)– and –C(O)N(R20)–. In some cases, S2is selected from –N(R20)–.

[0158] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each S2is independently selected from -C1-C6alkylene-C(O)-. In some cases, each S2is independently selected from -C1-C5alkylene-C(O)-. In some cases, each S2is independently selected from -C1-C4alkylene-C(O)-. In some cases, each S2is independently selected from -C1-C3alkylene-C(O)-. In some cases, each S2is independently selected from -C1-C2alkylene-C(O)-. In some cases, each S2is independently selected from -C2alkylene-C(O)-. In some cases, each S2is independently selected from -C1alkylene-C(O)-. In some cases, each S2is -C(O)-.

[0159] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), S2is selected from -C1-C6alkylene-C(O)-. In some cases, S2is selected from -C1-C5alkylene-C(O)-. In some cases, S2is selected from -C1-C4alkylene-C(O)-. In some embodiments, S2is selected from -C1-C3alkylene- C(O)-. In some cases, S2is selected from -C1-C2alkylene-C(O)-. In some embodiments, S2isselected from -C2alkylene-C(O)-. In some cases, S2is selected from -C1alkylene-C(O)-. In some embodiments, S2is -C(O)-.

[0160] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), S3is 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, S3is 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, S3is 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, S3is 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, S3is 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, S3is 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, S3is 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)2In some cases, S3is 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, S3is selected from an optionally substituted C1-C20alkylene wherein one or more alkylene units of the C1-C20alkylene are optionally and independently replaced by –C(O)–, –OC(O)–, –C(O)O–, –N(R20)–, or –C(O)N(R20)–. In some cases, S3isselected 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, S3is selected from an optionally substituted C1-C20alkylene 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, S3is selected from an optionally substituted C1-C10alkylene wherein one or more alkylene units of the C1-C10alkylene are optionally and independently replaced by –C(O)–, –OC(O)–, –C(O)O–, or – C(O)N(R20)–. In some cases, S3is 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, S3is selected from an optionally substituted C1-C20alkylene wherein one or more alkylene units of the C1-C20alkylene are optionally and independently replaced by –C(O)– or –C(O)N(R20)–. In some cases, S3is selected from an optionally substituted C1-C10alkylene wherein one or more alkylene units of the C1-C10alkylene are optionally and independently replaced by –C(O)– or –C(O)N(R20)–. In some cases, S3is 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, S3is selected from an optionally substituted C1-C20alkylene wherein one or more alkylene units of the C1-C20alkylene are optionally and independently replaced by –C(O)–. In some cases, S3is selected from an optionally substituted C1-C10alkylene wherein one or more alkylene units of the C1-C10alkylene are optionally and independently replaced by –C(O)–. In some cases, S3is 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, S3is selected from. In some cases, S3is selected from. In some cases, S3is selected from. In some cases, S3is

[0161] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), S3is 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, S3is 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, S3is selected from –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, and –C(O)–. In some cases, S3is selected from –NH–, –NHC(O)–, –C(O)NH–, and –C(O)–. In some cases, S3is selected from – NHC(O)–, –C(O)NH–, and –C(O)–. In some cases, S3is –C(O)–. In some cases, S3is selected from –N(R20)C(O)– and –C(O)N(R20)–. In some cases, S3is selected from –N(R20)–.

[0162] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), S3is selected from -C(O)-C1-C6alkylene-C(O)-. In some cases, S3is selected from -C(O)-C1-C5alkylene-C(O)-. In some embodiments, S3is selected from -C(O)-C1-C4alkylene-C(O)-. In some cases, S3is selected from -C(O)-C1-C3alkylene-C(O)-. In some cases, S3is selected from -C(O)-C1-C2alkylene-C(O)-. In some cases, S3is selected from -C(O)- C6alkylene-C(O)-. In some embodiments, S3is selected from -C(O)-C5alkylene-C(O)-. In some cases, S3is selected from -C(O)-C4alkylene-C(O)-. In some cases, S3is selected from -C(O)-C3alkylene-C(O)-. In some embodiments, S3is selected from -C(O)-C2alkylene-C(O)-. In some cases, S3is selected from -C(O)-C1alkylene-C(O)-.

[0163] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), S3is absent.

[0164] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula(XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), S3is selected from a spacer. In some cases, the spacer is a divalent moiety that covalently binds two components 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); alkoxy; 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-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, 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 optionally substituted with one or more of the substituents selected from halogen, -OR30, - N(R30)2, =O, and -CN. In some cases, S3is optionally substituted with one or more of the substituents selected from halogen, -OC1-6alkyl, -N(H)(C1-6alkyl), -N(C1-6alkyl)2, =O, and -CN. In some cases, S3is optionally substituted with one or more of the substituents selected from halogen, -OC1-6alkyl, and -CN. In some cases, S3is unsubstituted. In some cases, S3is substituted. In some cases, S3is a phenylene. In some cases, S3is

[0165] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each S4is independently absent or independently 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, each S4is independently absent or independently 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, each S4is independently absent or independently 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, each S4is independently absent or independently 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, each S4is independently absent or independently 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, each S4is independently absent or independently 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, each S4is independently absent or independently 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, each S4is independently absent or independently 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, each S4is independently absent or independently 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, each S4is independently absent or independently 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, each S4is independently absent or independently 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, each S4is independently absent or independently 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, each S4is independently absent or independently 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, each S4is independently absent or independently selected from. In some cases, each S4is independently selected fromand

[0166] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each S4is independently 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, each S4is independently 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, each S4is independently 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, each S4is independently 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, each S4is independently 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, each S4is independently 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, each S4is independently 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, each S4is independently 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, each S4is independently 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, each S4is independently 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, each S4is independently 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, each S4is independently 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, each S4is independently 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, each S4is independently selected fromand

[0167] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M),Formula (XXT-M-I), or Formula (XXT-M-II), 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 and independently replaced by –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)–, –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 fromIn some cases, S4is absent. In some cases, S4is 44 4In some cases, S isIn some cases, S isIn some cases, S is

[0168] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), 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, S4isselected 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 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 fromand. In some cases, S4is selected fromIn some cases, S4is selected from, In some cases, S4is. In some cases, S4isIn some cases, S4isIn some cases, S4is

[0169] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each S4is independently absent or independently 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, each S4is independently absent or independently 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, each S4is independently absent or independently selected from –N(R20)–, –N(R40)C(O)–, – C(O)N(R20)–, and –C(O)–. In some cases, each S4is independently absent or independently selected from –NH–, –NHC(O)–, –C(O)NH–, and –C(O)–. In some cases, each S4independently absent or is independently selected from –NHC(O)–, –C(O)NH–, and –C(O)–. In some cases, each S4is independently absent or –C(O)–. In some cases, each S4is independently selected from –N(R20)C(O)– and –C(O)N(R20)–. In some cases, each S4is independently absent or independently selected from –N(R20)–.

[0170] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each S4is independently 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, each S4is independently 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, each S4is independently selected from –N(R20)–, –N(R40)C(O)–, –C(O)N(R20)–, and –C(O)–. In some cases, each S4is independently selected from –NH–, –NHC(O)–, –C(O)NH–, and –C(O)–. In some cases, each S4is independently selected from –NHC(O)–, –C(O)NH–, and –C(O)–. In some cases, each S4is – C(O)–. In some cases, each S4is independently selected from –N(R20)C(O)– and –C(O)N(R20)–. In some cases, each S4is independently selected from –N(R20)–.

[0171] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), 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 selected from –N(R20)–.

[0172] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), 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)–.

[0173] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each S4is independently absent or independently selected from -C1-C6alkylene-C(O)-. In some cases, each S4is independently absent or independently selected from -C1-C5alkylene-C(O)-. In some cases, each S4is independently absent or independently selected from -C1-C4alkylene-C(O)-. In some cases, each S4is independently absent or independently selected from -C1-C3alkylene-C(O)-. In some cases, each S4is independently absent or independently selected from -C1-C2alkylene-C(O)-. In some cases, each S4is independently absent or independently selected from -C2alkylene-C(O)-. In some cases, each S4is independently absent or independently selected from -C1alkylene-C(O)-. In some cases, each S4is independently absent or independently selected from -C(O)-.

[0174] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each S4is independently selected from -C1-C6alkylene-C(O)-. In some cases, each S4is independently selected from -C1-C5alkylene-C(O)-. Insome cases, each S4is independently selected from -C1-C4alkylene-C(O)-. In some cases, each S4is independently selected from -C1-C3alkylene-C(O)-. In some cases, each S4is independently selected from -C1-C2alkylene-C(O)-. In some cases, each S4is independently selected from -C2alkylene-C(O)-. In some cases, each S4is independently selected from -C1alkylene-C(O)-. In some cases, each S4is independently selected from -C(O)-.

[0175] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), 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)-.

[0176] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), S4is selected from -C1-C6alkylene-C(O)-. In some cases, S4is selected from -C1-C5alkylene-C(O)-. In some cases, S4is selected from -C1-C4alkylene-C(O)-. In some embodiments, S4is selected from -C1-C3alkylene-C(O)-. In some cases, S4is selected from -C1-C2alkylene-C(O)-. In some embodiments, S4is selected from -C2alkylene-C(O)-. In some cases, S4is -C1alkylene-C(O)-. In some embodiments, S4is -C(O)-.

[0177] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), J is 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, J is selected from an optionallysubstituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, –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, J is 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)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, J is 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)2N(R20)–, –O– , –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–. In some cases, J is 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)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–. In some cases, J is 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)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, or –S(O)2–. In some cases, J is 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)–, –O–, –C(O)–, – OC(O)–, –C(O)O–, or –C(O)N(R20)–. In some cases, J is selected from an optionally substituted C1-C20alkylene wherein one or more alkylene units of the C1-C20alkylene are optionally and independently replaced by –N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, or –C(O)N(R20)–. In some cases, J is 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)–, – O–, or –C(O)N(R20)–. In some cases, J is selected from an optionally substituted C1-C20alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, –O–, –C(O)–, or –C(O)N(R20)–. In some cases, J is selected from an optionally substituted C1-C10alkylene wherein one or more alkylene units of the C1-C10alkylene are optionally and independently replaced by –N(R20)–, –O–, or –C(O)N(R20)–. In some cases, J is 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)– or –O–. In some cases, J is selected from an optionally substituted C1-C20alkylene wherein one or more alkylene units of the C1-C20alkylene are optionally and independently replaced by –N(R20)– or –O–. In some cases, J is selected from an optionally substituted C1-C15alkylene wherein one or more alkylene units of the C1-C15alkylene are optionally and independently replaced by –N(R20)– or – O–. In some cases, J is selected from an optionally substituted C1-C10alkylene wherein one or more alkylene units of the C1-C10alkylene are optionally and independently replaced by – N(R20)– or –O–. In some cases, J is selected fromIn some cases, the J is a trivalent moiety that covalently binds three components of the conjugate or Drug-Linker.

[0178] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), J is 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, J is 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)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, J is 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)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, J is 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)2N(R20)–, –O– , –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–. In some cases, J is 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)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, –S–, –S(O)–, or –S(O)2–. In some cases, J is 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)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, or –S(O)2–. In some cases, J is 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)–, –O–, –C(O)–, – OC(O)–, –C(O)O–, or –C(O)N(R20)–. In some cases, J is selected from an optionally substituted C1-C20alkylene wherein one or more alkylene units of the C1-C20alkylene are optionally and independently replaced by –N(R20)–, –O–, –C(O)–, –OC(O)–, –C(O)O–, or –C(O)N(R20)–. In some cases, J is 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)–, –O–, or –C(O)N(R20)–. In some cases, J is selected from an optionally substituted C1-C20alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(R20)–, –O–, –C(O)–, or –C(O)N(R20)–. In some embodiments, J is selected from an optionally substituted C1-C10alkylene wherein one or more alkylene units of the C1-C10alkylene are optionally and independently replaced by –N(R20)–, –O–, or –C(O)N(R20)–. In some cases, J is 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)– or – O–. In some cases, J is selected from an optionally substituted C1-C20alkylene wherein one or more alkylene units of the C1-C20alkylene are optionally and independently replaced by – N(R20)– or –O–. In some cases, J is selected from an optionally substituted C1-C15alkylene wherein one or more alkylene units of the C1-C15alkylene are optionally and independently replaced by –N(R20)– or –O–. In some cases, J is selected from an optionally substituted C1-C10alkylene wherein one or more alkylene units of the C1-C10alkylene are optionally and independently replaced by –N(R20)– or –O–. In some cases, J is selected from an optionally substituted C1-C30alkylene wherein one or more alkylene units of the C1-C30alkylene are optionally and independently replaced by –N(H)– or –O–. In some cases, J is selected from an optionally substituted C1-C20alkylene wherein one or more alkylene units of the C1-C20alkylene are optionally and independently replaced by –N(H)– or –O–. In some cases, J is selected from an optionally substituted C1-C15alkylene wherein one or more alkylene units of the C1-C15alkylene are optionally and independently replaced by –N(H)– or –O–. In some cases, J is selected from an optionally substituted C1-C10alkylene wherein one or more alkylene units of the C1-C10alkylene are optionally and independently replaced by –N(H)– or –O–. In some cases, S3is selected fromIn some cases, S3is selected fromIn some cases, J is selected fromIn some cases, J is selected fromIn some cases, the J is a divalent moiety that covalently binds two components of the conjugate or Drug-Linker.

[0179] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), J is 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, J is 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, J is selected from –N(R20)–, –N(R20)C(O)–, –C(O)N(R20)–, and –C(O)–. In some cases, J is selected from –NH–, –NHC(O)–, –C(O)NH–, and –C(O)–. In some cases, J is selected from –NHC(O)–, – C(O)NH–, and –C(O)–. In some cases, J is –C(O)–. In some cases, J is selected from – N(R20)C(O)– and –C(O)N(R20)–. In some cases, J is selected from –N(R20)–. In some cases, the J is a divalent moiety that covalently binds two components of the conjugate or Drug-Linker. In some cases, the J is a trivalent moiety that covalently binds three components of the conjugate or Drug-Linker.

[0180] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), J is selected from -C1-C6alkylene-O-C1-C6alkylene-O-C1-C6alkylene- N(S3)-C1-C6alkylene-O-C1-C6alkylene-O-C1-C6alkylene-. In some cases, J is selected from -C1-C6alkylene-O-C1-C5alkylene-O-C1-C6alkylene-N(S3)-C1-C5alkylene-O-C1-C5alkylene-O-C1-C6alkylene-. In some cases, J is selected from -C1-C6alkylene-O-C1-C4alkylene-O-C1-C4alkylene- N(S3)-C1-C4alkylene-O-C1-C4alkylene-O-C1-C6alkylene-. In some cases, S3is selected from - C1-C6alkylene-O-C1-C3alkylene-O-C1-C6alkylene-N(S3)-C1-C3alkylene-O-C1-C3alkylene-O-C1-C3alkylene-. In some cases, J is selected from -C1-C2alkylene-O-C1-C2alkylene-O-C1-C2alkylene-N(S3)-C1-C2alkylene-O-C1-C2alkylene-O-C1-C2alkylene-. In some cases, J is selected from -C1-C6alkylene-O-C2alkylene-O-C2alkylene-N(S3)-C2alkylene-O-C2alkylene-O-C1-C6alkylene-. In some cases, J is selected from -C2alkylene-O-C2alkylene-O-C2alkylene-N(S3)-C2alkylene-O-C2alkylene-O-C2alkylene-. In some cases, the J is a divalent moiety that covalently binds two components of the conjugate or Drug-Linker. In some cases, the J is a trivalent moiety that covalently binds three components of the conjugate or Drug-Linker. In some cases, S3is absent and J forms a bond with M1(e.g., by way of example only: -C1-C6alkylene-O-C1-C6alkylene-O-C1-C6alkylene-N(M1)C1-C6alkylene-O-C1-C6alkylene-O-C1-C6alkylene-).

[0181] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I),or Formula (XXT-M-II), J is selected from -C1-C6alkylene-O-C1-C6alkylene-O-C1-C6alkylene- N(S3)(R20). In some cases, J is selected from -C1-C6alkylene-O-C1-C5alkylene-O-C1-C6alkylene-N(S3)(R20). In some cases, J is selected from -C1-C6alkylene-O-C1-C4alkylene-O-C1-C4alkylene-N(S3)(R20). In some cases, S3is selected from -C1-C6alkylene-O-C1-C3alkylene-O-C1-C6alkylene-N(S3) (R20). In some cases, J is selected from -C1-C2alkylene-O-C1-C2alkylene-O- C1-C2alkylene-N(S3)(R20). In some cases, J is selected from -C1-C6alkylene-O-C2alkylene-O-C2alkylene-N(S3)(R20). In some cases, J is selected from -C2alkylene-O-C2alkylene-O-C2alkylene-N(S3)(R20). In some cases, J is selected from -C1-C6alkylene-O-C1-C6alkylene-O-C1-C6alkylene-N(S3)(H). In some cases, J is selected from -C1-C6alkylene-O-C1-C5alkylene-O-C1-C6alkylene-N(S3)(H). In some cases, J is selected from -C1-C6alkylene-O-C1-C4alkylene-O-C1-C4alkylene-N(S3)(H). In some cases, J is selected from -C1-C6alkylene-O-C1-C3alkylene-O-C1-C6alkylene-N(S3)(H). In some cases, J is selected from -C1-C2alkylene-O-C1-C2alkylene-O-C1-C2alkylene-N(S3)(H). In some cases, J is selected from -C1-C6alkylene-O-C2alkylene-O-C2alkylene-N(S3)(H). In some cases, J is selected from -C2alkylene-O-C2alkylene-O-C2alkylene- N(S3)(H). In some cases, the J is a divalent moiety that covalently binds two components of the conjugate or Drug-Linker. In some cases, the J is a trivalent moiety that covalently binds three components of the conjugate or Drug-Linker. In some cases, S3is absent and J forms a bond with M1(e.g., by way of example only: -C1-C6alkylene-O-C1-C6alkylene-O-C1-C6alkylene- N(M1)(R20) or -C1-C6alkylene-O-C1-C6alkylene-O-C1-C6alkylene-NH(M1) ).

[0182] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), J is selected from phenylene. In some cases, the J is a divalent moiety that covalently binds two components of the conjugate or Drug-Linker. In some cases, the J is a trivalent moiety that covalently binds three components of the conjugate or Drug-Linker.

[0183] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula(XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), J is absent. In some cases, J is absent and S3forms a bond with S1. In some cases, J is absent and S3forms two independent bonds with two S1.

[0184] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), J is selected from a joiner. In some cases, the joiner is a divalent moiety that covalently binds two components of the conjugate or Drug-Linker. In some cases, the joiner is a trivalent moiety that covalently binds three components of the conjugate or Drug- Linker. In some cases, J is present. In some cases, J is absent. In some cases, the joiner 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); alkoxy; 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 joiner is a divalent linear alkylene group. In some cases, a joiner is a trivalent linear alkylene group. In some cases, a joiner is a trivalent branched alkylene group. In some cases, the joiner 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, J is 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, J is 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, J is optionally substituted with one or more of the substituents selected from (i) halogen, -OR30, - N(R30)2, =O, and -CN. In some cases, J is unsubstituted. In some cases, J is substituted. In some cases, J is a phenylene. In some cases, J is selected from

[0185] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), J-S3is selected fromIn some cases, J-S3is selected fromIn some cases, J- S3is selected from. In some cases, J-S3is selectedIn some cases, the J-S3is a trivalent moiety that covalently binds three components of the conjugate or Drug-Linker.

[0186] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), J-S3is selected from. In some cases, J-S3In some cases, the J-S3is a divalent moiety that covalently binds two components of the conjugate or Drug-Linker.

[0187] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II),is selected fromIn some cases,is selected from. In some cases,is selected from .In some cases,is a trivalent moiety that covalently binds three components of the conjugate or Drug-Linker.

[0188] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II),is selected fromIn some cases,is a divalent moiety that covalently binds two components of the conjugate or Drug-Linker.

[0189] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II),is selected from. In some cases,In some cases, theis a trivalent moiety that covalently binds three components of the conjugate or Drug-Linker.

[0190] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II),is selected fromsome cases, theis a divalent moiety that covalently binds two components of the conjugate or Drug-Linker.

[0191] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each Y1is independentlyselected fromand each K1is independently selected from a peptide unit. In some cases, each peptide unit is independently 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, and; andT is selected from -OH, -NH2andIn some cases, each R10is selected from hydrogen, and methyl. In some cases, each peptide unit is independently represented byIn 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 by, ,In 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 Y1isIn some cases, each Y1is.

[0192] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), orfor a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Y1is selected fromand K1is 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, and; andT is selected from -OH, -NH2andIn 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 from hydrogen and methyl. In some cases, the peptide unit is represented byIn some cases, each n is selected from 5 to 12. In some cases, eachn 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 selectedfrom 5 and 10. In some cases, Y1isIn some cases, Y1is

[0193] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each Y1-S4-K2is independently selected from 2and each K is independentlyselected from KB. In some cases, each KBis independently 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. In some cases, each Y1-S4-K2is independently selected fromand each K2is independently selected from KB. In some cases, each Y1-S4-K2is independently selected fromand each K2is independently selected from KB. In some cases, each Y1-S4-K2is independently selected fromandand each K2is independently selected from KB. In some cases, each Y1-S4-K2is independently selected fromand each K2is independently selected from KB. In some cases, each KBis independently selected from a peptide unit. In some cases, each peptide unit is independently 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, andand T is selected from -OH, -NH2,In 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 byIn 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.

[0194] In some embodiments for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), Y1-S4-K2is selected from 2Band K is selected from K . 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. In some cases, Y1-S4-K2is selected fromand K2is selected from KB. In some cases, Y1-S4-K2is selected fromand K2is selected from KB. In some cases, Y1-S4-K2is selected from 2and K is selected from KB. In some cases, Y1-S4-K2is selected fromand K2is 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, and; andT is selected from -OH, -NH2,In 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 byIn 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.

[0195] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each Y1-S4-K2is independently selected from 2and each K is independentlyselected from KL. In some cases, each KLis independently 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. In some cases, each Y1-S4-K2is independently selected fromand each K2is independently selected from KL. In some cases, each Y1-S4-K2is independently selected fromand each K2is independently selected from KL. In some cases, each KLis independently selected from a peptide unit. In some cases, each peptide unit is independently 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, and; andT is selected from C1-6alkyl.In 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 byIn 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 somecases, n is 10. In some cases, each n is selected from 5 and 10.

[0196] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), Y1-S4-K2is selected from 2Land K is selected from K . In some cases, KLis 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. In some cases, Y1-S4-K2is selectedfromand K2is selected from KL. In some cases, Y1-S4-K2is selected from; and K2is selected from KL. In some cases, Y1-S4-K2is selected fromand K2is selected from KL. In some cases, Y1-S4-K2is selected from2 L Land K is selected from K. In some cases, K is 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 C alkyl;1-610each R is independently selected from hydrogen, methyl, isopropyl, isobutyl, sec-butyl, benzyl, p-hydroxybenzyl, -CHOH, -CH(OH)CH, -CHCHSCH, -CHCONH, -2 3 2 2 3 2 2CHCOOH, -CHCHCONH, -CHCHCOOH, -CHCHCHCOOH, -2 2 2 2 2 2 2 2 2(CH)NHC(=NH)NH, -(CH)NH, -(CH)NHCOCH, -(CH)NHCHO, -23 2 23 2 23 3 23(CH)NHC(=NH)NH, -(CH)NH, -(CH)NHCOCH, -(CH)NHCHO, -24 2 24 2 24 3 24(CH)NHCONH, -(CH)NHCONH, -CHCHCH(OH)CHNH, 2-pyridylmethyl-, 3-23 2 24 2 2 2 2 2pyridylmethyl-, 4-pyridylmethyl-, phenyl, cyclohexyl, and ; and T is selected from C- alkyl.1610In some cases, each R is 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 from hydrogen and methyl. In some cases, each peptide unit is independently represented byIn 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.

[0197] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), 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.

[0198] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), 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-K2or -K2(i.e., if S4is absent). In some cases, the peptide cleavable unit further comprises at least one -S4-K2. In some cases, the peptide cleavable unit further comprises at least one -K2. In some cases, the peptide cleavable unit further comprises one -S4- K2. In some cases, the peptide cleavable unit further comprises one -K2. In some cases, K2is 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, K2is selected from KB. In some cases, K2is 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-K2is selected from S4-KB. In some cases, each S4-K2is independently selected from S4-KB. In some cases, -K2is selected from -KB. In some cases, each -K2is independently selected from -KB. In some cases, S4-K2is selected from S4-KL. In some cases, each S4-K2is independently selected from S4-KL. In some cases, -K2is selected from -KL. In some cases, each -K2is independently selected from - KL.

[0199] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), cleavage of the cleavable unit triggers self -immolation of the phenyl- comprising linker of the compounds of the invention, and release of the Drug unit (D).

[0200] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula(XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each sugar cleavable unit of T1independently includes a sugar. In some cases, each sugar is glucuronide. In some cases, each sugar is independently selected from fructose, galactose glucose, xylose and ribose. In some cases, each sugar is independently selected from a monosaccharide. In some cases, each sugar is independently selected from a disaccharide.

[0201] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), 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 selected from a monosaccharide. In some cases, the sugar is selected from a disaccharide.

[0202] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each Y1isIn some cases, each Y1is a sugar moiety. In some cases, each Y1is absent. In some cases, one Y1is absent. In some cases, Y1isIn some cases, Y1is a sugar moiety. In some cases, Y1is absent.

[0203] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each peptide unit of T2independently includes 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, each peptide unit of T2independently includes 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, each peptide unit of T2independently includes a dipeptide or tripeptide. In some cases, each peptide unit of T2independently includes a dipeptide. In some cases, each dipeptide is independently selected from Val-Cit, Val-Ala and Phe-Lys. In some cases, each peptide unit of T2independently, further comprises at least one -S4-K2or -K2(i.e., if S4is absent). In some cases, each peptide unit of T2independently, further comprises at least one -S4-K2. In some cases, each peptide unit of T2independently, further comprises at least one -K2. In some cases, each peptide unit of T2independently, further comprises one -S4-K2. In some cases, each peptide unit of T2independently, further comprises one -K2. In some cases, each K2is independently selected from KBand KL. In some cases, each peptide unit of T2independently, further comprises at least one -S4-KB, -S4-KL, -KB, or -KL(i.e., if S4is absent). In some cases, each K2is independently selected from KB. In some cases, each K2is independently selected from KL. In some cases, each peptide unit of T2independently, further comprises at least one -S4-KBor -KB(i.e., if S4is absent). In some cases, each peptide unit of T2independently, further comprises at least one -S4-KLor -KL(i.e., if S4is absent). In some cases, each S4-K2is independently selected from S4-KB. In some cases, each -K2is independently selected from -KB. In some cases, each S4- K2is independently selected from S4-KL. In some cases, each -K2is independently selected from -KL.

[0204] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), Formula (X-M-II), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX- D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), 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-K2or -K2(i.e., if S4is absent). In some cases, the peptide unit of T2further comprises at least one -S4-K2. In some cases, the peptide unit of T2further comprises at least one -K2. In some cases, the peptide unit of T2further comprises one -S4-K2. In some cases, the peptide unit of T2further comprises one -K2. In some cases, K2is 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, K2is selected from KB. In some cases, K2is 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-K2is selected from S4-KB. In some cases, -K2is selected from -KB. In some cases, S4-K2is selected from S4-KL. In some cases, -K2is selected from -KL.

[0205] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each peptide unit of T2independently includes a capping moiety. In some cases, each capping moiety is independently a moiety capable of reacting with an amine of each peptide to form an amide, carbamate or sulfonamide. In some cases, each capping moiety is independently a moiety which results from reacting with an amine to form an amide, carbamate or sulfonamide. In some cases, each capping moiety is independently a moiety which results from reacting with an amine to form an amide. In some cases, each capping moiety is independently a moiety which caps the end of a / an peptide / amino acid. In some cases, each capping moiety is. In some cases, each Y1is.

[0206] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), orfor a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), 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, Y1is.

[0207] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each peptide unit of T2independently includes a capping moiety. In some cases, each capping moiety is independently a moiety capable of reacting with an amine of the peptide to form an amide, carbamate or sulfonamide. In some cases, each capping moiety is independently a moiety which results from reacting with an amine to form an amide, carbamate or sulfonamide. In some cases, each capping moiety is independently a moiety which results from reacting with an amine to form an amide. In some cases, each capping moiety is independently a moiety which caps the end of a / an peptide / amino acid. In some cases, each capping moiety is independently selected from an acyl moiety. In some cases, each capping moiety is selected from, wherein each R* is independently selected from C1-6alkyl. In some cases, each capping moiety isIn some cases, each Y1is independently selected from, wherein each R* is independently selected from C1-6alkyl. In some cases, each Y1is

[0208] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), 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 selected fromwherein R* is selected from C1-6alkyl. In some cases, the capping moiety is. In some cases, Y1is selected from, wherein R* is selected from C1-6alkyl. In some cases, Y1is

[0209] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each peptide unit of T2independently, further comprises at least one -S4-K2or -K2(i.e., if S4is absent). In some cases, each peptide unit of T2independently, further comprises at least one -S4-K2. In some cases, each peptide unit of T2independently, further comprises at least one -K2. In some cases, each peptide unit of T2independently, further comprises one -S4-K2. In some cases, each K2is selected from KBand KL. In some cases, each peptide unit of T2independently, further comprises at least one -S4-KB, -S4- KL, -KB, or -KL(i.e., if S4is absent). In some cases, each K2is selected from KB. In some cases, each K2is selected from KL. In some cases, each peptide unit of T2independently, further comprises at least one -S4-KBor -KB(i.e., if S4is absent). In some cases, each peptide unit of T2independently, further comprises at least one -S4-KLor -KL(i.e., if S4is absent). In some cases, each S4-K2is independently selected from S4-KB. In some cases, each -K2is independently selected from -KB. In some cases, each S4-K2is independently selected from S4-KL. In somecases, each -K2is independently selected from -KL. In some cases, each peptide unit of T2independently, further comprises one -K2. In some cases, each Y1-S4-K2is independently selected fromIn some cases, each Y1-S4-K2is independently selected fromindependently selected from. In some cases, each S4is independently absent or independently selected from. In some cases, each S4is absent. In some cases, each S4is independently selected from,, In some cases, each S4is independently selected fromandIn some cases, each S4is In some cases, each S4isIn some cases, each S4is. In some cases, each Y1-S4-K2is independently selected fromIn some cases, each Y1- S4-K2is independently selected fromIn1 4 2some cases, each Y -S -K is independently selected fromIn some cases, each Y1-S4- K2is independently selected fromIn some cases, each Y1-S4-K2is independently selected from.In some cases, each Y1-S4-K2isindependently includes a capping moiety. In some cases, each K2is independently selected from KBand KL. In some cases, each KBand each KLindependently include a capping moiety. In some cases, each KLindependently includes a capping moiety. In some cases, each KBindependently includes a capping moiety. In some cases, each capping moiety is a moiety capable of independently reacting with an amine of each KBor each KLto independently form an amide, carbamate or sulfonamide. In some cases, each capping moiety is independently a moiety which results from reacting with an amine to form an amide, carbamate or sulfonamide. In some cases, each capping moiety is independently a moiety which results from reacting with an amine to form an amide. In some cases, each capping moiety is independently a moiety which independently caps the end of a / an peptide / amino acid of each KBand each KL. In some cases, each capping moiety is independently an acyl moiety. In some cases, each capping moiety is independently selected fromwherein each R* is independently selected from C1-6alkyl. In some cases, each capping moiety is

[0210] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), the peptide unit of T2further comprises at least one -S4-K2or -K2(i.e., if S4is absent). In some cases, the peptide unit of T2further comprises at least one -S4-K2. In some cases, the peptide unit of T2further comprises at least one -K2. In some cases, the peptide unit of T2further comprises one -S4-K2. In some cases, K2is 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, K2is selected from KB. In some cases, K2is 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-K2is selected from S4-KB. In some cases, each S4-K2is independently selected from S4-KB. In some cases, -K2is selected from -KB. In some cases, each -K2is independently selected from -KB. In some cases, S4-K2is selected from S4-KL. In some cases, each S4-K2is independently selected from S4-KL. In some cases, -K2is selected from -KL. In some cases, each -K2is independently selected from -KL. In some cases, the peptide unit of T2further comprises one -K2. In some cases, Y1-S4-K2is selected fromIn some cases, S4is absent or selected fromsome cases, S4isIn some cases, Y1-S4-K2is selected fromK2is selected fromIn some cases, Y1-S4-K2is selectedIn some cases, each Y1-S4-K2is independently selected fromIn some cases, K2includes a capping moiety. In some cases, K2is 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 some cases, the capping moiety is a moiety which caps the end of a / an peptide / amino acid of KBor KL. In some cases, the capping moiety is an acyl moiety. In some cases, the capping moiety is selected fromwherein R* is selected from C1-6alkyl. In some cases, the capping moiety is

[0211] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), K1is selected from a peptide unit. In some cases, the peptide unit is a residue.

[0212] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), the peptide unit of each K1independently has 1 to 50 amino acids. In some cases, the peptide unit of each K1independently has 1 to 20 amino acids. In some cases, the peptide unit of each K1independently has 1 to 10 amino acids. In some cases, the peptide unit of each K1independently has 2 to 50 amino acids. In some cases, the peptide unit of each K1independently has 2 to 40 amino acids. In some cases, the peptide unit of each K1independently has 2 to 30 amino acids. In some cases, the peptide unit of each K1independently has 2 to 20 amino acids. In some cases, the peptide unit of each K1independently has 2 to 10 amino acids. In some cases, the peptide unit of each K1independently has 5 to 10 amino acids. In some cases, the peptide unit of each K1independently has at least 1 amino acid. In some cases, the peptide unit of each K1independently has 1 amino acid. In some cases, the peptide unit of each K1independently has at least 2 amino acids. In some cases, the peptide unit of each K1independently has at least 5 amino acids. In some cases, the peptide unit of each K1independently has at least 8 amino acids. In some cases, the peptide unit of each K1independently has at least 10 amino acids. In some cases, the peptide unit of each K1independently has at most 10 amino acids. In some cases, the peptide unit of each K1independently has 10 amino acids. In some cases, the peptide unit of each K1independently has at least 12 amino acids. In some cases, the peptide unit of each K1independently has at most 12 amino acids. In some cases, the peptide unit of each K1independently has at least 20 amino acids. In some cases, the peptide unit of each K1independently has at most 20 amino acids. In some cases, the peptide unit of each K1independently has 20 amino acids. In some cases, the peptide unit of each K1independently has at most 30 amino acids. In some cases, the peptide unit of each K1independently has at least 30 amino acids. In some cases, the amino acids of each K1are independently 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 each K1are independently 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 each K1are independently 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 each K1are independently selected from a group consisting of glycine, sarcosine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of each K1are independently selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of each K1independently are selected from a group consisting of glycine, proline, serine, alanine, and β -Alanine. In some cases, each K1independently includes at least one glycine. In some cases, each K1independently includes at least one proline. In some cases, each K1independently includes at least one serine. In some cases, each K1independently includes at least one alanine. In some cases, each K1independently includes at least one β-Alanine. In some cases, each K1is independently a polysarcosine. In some cases, each K1is independently a polysarcosine with ten repeating sarcosine units. In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D- I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D-II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), the peptide unit of K1has 1 to 50 amino acids. In some cases, the peptide unit of K1has 1 to 20 amino acids. In some cases, the peptide unit of K1has 1 to 10 amino acids. In some cases, the peptide unit of K1has 2 to 50 amino acids. In some cases, the peptide unit of K1has 2 to 40 amino acids. In some cases, the peptide unit of K1has 2 to 30 amino acids. In some cases, the peptide unit of K1has 2 to 20 amino acids. In some cases, the peptide unit of K1has 2 to 10 amino acids. In some cases, the peptide unit of K1has 5 to 10 amino acids. In some cases, the peptide unit of K1has at least 1 amino acid. In some cases, the peptide unit of K1has 1 amino acid. In some cases, the peptide unit of K1has at least 2 amino acids. In some cases, the peptide unit of K1has at least 5 amino acids. In some cases, the peptide unit of K1has at least 8 amino acids. In some cases, the peptide unit of K1has at least 10 amino acids. In some cases, the peptide unit of K1has at most 10 amino acids. In some cases, the peptide unit of K1has 10 amino acids. In some cases, the peptide unit of K1has at least 12 amino acids. In some cases, the peptide unit of K1has at most 12 amino acids. In some cases, the peptide unit of K1has at least 20 amino acids. In some cases, the peptide unit of K1has at most 20 amino acids. In some cases, the peptide unit of K1has 20 amino acids. In some cases, the peptide unit of K1has at most 30 amino acids. In some cases, thepeptide unit of K1has at least 30 amino acids. In some cases, the amino acids of K1are 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 K1are 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 K1are 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 K1are selected from a group consisting of glycine, sarcosine, proline, serine, alanine, and β -Alanine. In some cases, the amino acids of K1are selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of K1are selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, K1includes at least one glycine. In some cases, K1includes at least one proline. In some cases, K1includes at least one serine. In some cases, K1includes at least one alanine. In some cases, K1includes at least one β-Alanine. In some cases, K1is a polysarcosine. In some cases, K1is a polysarcosine with ten repeating sarcosine units.

[0213] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each K1is independently selected from a peptide unit, wherein the peptide unit has a terminal -NH2. In some cases, each K1independently is selected from a peptide unit, wherein the peptide unit has a terminal -OH. In some cases, each K1independently is selected from a peptide unit, wherein the peptide unit has a terminal. In some cases, each K1independently is selected from a peptide, wherein the peptide has a terminal -NH2. In some cases, each K1independently is selected from a peptide, wherein the peptide has a terminal -OH. In some cases, each K1independently is selected from a peptide, wherein the peptide has a terminal.

[0214] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), K1is selected from a peptide unit, wherein the peptide unit has a terminal -NH2. In some cases, K1is selected from a peptide unit, wherein the peptide unit has a terminal -OH. In some cases, K1is selected from a peptide unit, wherein the peptide unit has a terminal. In some cases, K1is selected from a peptide, wherein the peptide has a terminal -NH2. In some cases, K1is selected from a peptide, wherein the peptide has a terminal -OH. In some cases, K1is selected from a peptide, wherein the peptide has a terminal.

[0215] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each K1independently is selected from a peptide unit. In some cases, the peptide unit of each K1independently has 1 to 50 amino acids. In some cases, the peptide unit of each K1independently has 1 to 20 amino acids. In some cases, the peptide unit of each K1independently has 1 to 10 amino acids. In some cases, the peptide unit of each K1independently has 2 to 50 amino acids. In some cases, the peptide unit of each K1independently has 2 to 40 amino acids. In some cases, the peptide unit of each K1independently has 2 to 30 amino acids. In some cases, the peptide unit of each K1independently has 2 to 20 amino acids. In some cases, the peptide unit of each K1independently has 2 to 10 amino acids. In some cases, the peptide unit of each K1independently has 5 to 10 amino acids. In some cases, the peptide unit of each K1independently has at least 1 amino acids. In some cases, the peptide unit of each K1independently has 1 amino acid. In some cases, the peptide unit of each K1independently has at least 2 amino acids. In some cases, the peptide unit of each K1independently has at least 5 amino acids. In some cases, the peptide unit of each K1independently has at least 8 amino acids. In some cases, the peptide unit of each K1independently has at least 10 amino acids. In some cases, the peptide unit of each K1independently has at most 10 amino acids. In some cases, the peptide unit of each K1independently has 10 amino acids. In some cases, the peptide unit of each K1independently has at least 12 amino acids. In some cases, the peptide unit of each K1independently has at most 12amino acids. In some cases, the peptide unit of each K1independently has at least 20 amino acids. In some cases, the peptide unit of each K1independently has at most 20 amino acids. In some cases, the peptide unit of each K1independently has 20 amino acids. In some cases, the peptide unit of each K1independently has at most 30 amino acids. In some cases, the peptide unit of each K1independently has at least 30 amino acids. In some cases, each K1is independently a peptide unit selected from a glycine and two adjacent sarcosines. In some cases, each K1is independently a peptide unit selected from a glycine and three adjacent sarcosines. In some cases, each K1is independently 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, each K1independently includes a glycine and two adjacent sarcosines. In some cases, each K1independently includes a glycine and three adjacent sarcosines. In some cases, each K1independently includes a glycine and four adjacent sarcosines. In some cases, each K1independently is a peptide unit selected from a glycine and two adjacent sarcosines. In some cases, each K1is independently a peptide unit selected from a glycine and three adjacent sarcosines. In some cases, each K1is independently a peptide unit selected from a glyicine and four adjacent sarcosines. In some cases, each K1independently includes 2 glycines and 8 sarcosines. In some cases, each K1independently includes 3 glycines and 8 sarcosines. In some cases, each K1independently includes 4 glycines and 7 sarcosines. In some cases, each K1independently includes 3 glycines and 7 sarcosines. In some cases, each K1independently includes 3 glycines and 6 sarcosines. In some cases, each K1independently includes 3 glycines and 5 sarcosines. In some cases, each K1independently includes 3 glycines and 4 sarcosines. In some cases, each K1independently includes 3 glycines and 3 sarcosines. In some cases, each K1independently includes 3 glycines and 9 sarcosines. In some cases, each K1independently includes 3 glycines and 10 sarcosines. In some cases, each K1independently includes 5 glycines and 5 sarcosines. In some cases, each K1independently includes 4 glycines and 4 sarcosines. In some cases, each K1independently includes 4 glycines and 5 sarcosines. In some cases, each K1independently includes 5 glycines and 4 sarcosines. In some cases, each K1independently has at most 9 sarcosines. In some cases, each K1independently has at most 8 sarcosines. In some cases, each K1independently has at most 7 sarcosines. In some cases, each K1independently has at most 6 sarcosines. In some cases, each K1independently has at most 5 sarcosines. In some cases, each K1independently has at most 4 sarcosines. In some cases, each K1independently has at most 3 sarcosines. In some cases, each K1independently has at most 2 sarcosines. In some cases, each K1independently has at most 1 sarcosine. In some cases, each K1independently has at most 9 glycines. In some cases, each K1independently has at most 8 glycines. In some cases, each K1independently has at most 7 glycines. In some cases, each K1independently has at most 6 glycines. In some cases, each K1independently has at most 5 glycines. In some cases, each K1independently has at most 4 glycines. In some cases, each K1independently has at most 3 glycines. In some cases, each K1independently has at most 2 glycines. In some cases, each K1independently has at most 1 glycine. In some cases, the amino acids of each K1are independently 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 each K1are independently selected from a group consisting of alanine, arginine, asparagine, aspartic ac id, 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 each K1are independently 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 each K1are independently selected from a group consisting of glycine, sarcosine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of each K1are independently selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of each K1are independently selected from a group consisting of proline, serine, alanine, and β-Alanine. In some cases, the amino acids of each K1independently includes at least one glycine and at least one other amino acid. In some cases, the amino acids of each K1independently includes at least one glycine and at least one sarcosine. In some cases, the amino acids of each K1independently includes 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 each K1are independently selected from a group consisting of glycine, proline, serine, alanine, and β - Alanine. In some cases, each K1independently includes at least one glycine. In some cases, each K1independently includes at least one proline. In some cases, each K1independently includes at least one serine. In some cases, K1includes at least one alanine. In some cases, each K1independently includes at least one β-Alanine.

[0216] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), K1is selected from a peptide unit. In some cases, the peptide unit of K1has 1 to 50 amino acids. In some cases, the peptide unit of K1has 1 to 20 amino acids. In some cases, the peptide unit of K1has 1 to 10 amino acids.In some cases, the peptide unit of K1has 2 to 50 amino acids. In some cases, the peptide unit of K1has 2 to 40 amino acids. In some cases, the peptide unit of K1has 2 to 30 amino acids. In some cases, the peptide unit of K1has 2 to 20 amino acids. In some cases, the peptide unit of K1has 2 to 10 amino acids. In some cases, the peptide unit of K1has 5 to 10 amino acids. In some cases, the peptide unit of K1has at least 1 amino acids. In some cases, the peptide unit of K1has 1 amino acid. In some cases, the peptide unit of K1has at least 2 amino acids. In some cases, the peptide unit of K1has at least 5 amino acids. In some cases, the peptide unit of K1has at least 8 amino acids. In some cases, the peptide unit of K1has at least 10 amino acids. In some cases, the peptide unit of K1has at most 10 amino acids. In some cases, the peptide unit of K1has 10 amino acids. In some cases, the peptide unit of K1has at least 12 amino acids. In some cases, the peptide unit of K1has at most 12 amino acids. In some cases, the peptide unit of K1has at least 20 amino acids. In some cases, the peptide unit of K1has at most 20 amino acids. In some cases, the peptide unit of K1has 20 amino acids. In some cases, the peptide unit of K1has at most 30 amino acids. In some cases, the peptide unit of K1has at least 30 amino acids. In some cases, K1is a peptide unit selected from a glycine and two adjacent sarcosines. In some cases K 1 is apeptide unit selected from a glycine and three adjacent sarcosines. In some cases, K1is a peptide unit selected from a glyicine and four adjacent sarcosines. In some cases, when a peptide unitincludes adjacent sarcosines, there is at least one other amino acid present. In some cases, K 1includes a glycine and two adjacent sarcosines. In some cases, K1includes a glycine and three adjacent sarcosines. In some cases, K1includes a glycine and four adjacent sarcosines. In some cases, K1is a peptide unit selected from a glycine and two adjacent sarcosines. In some cases K1is a peptide unit selected from a glycine and three adjacent sarcosines. In some cases, K1is a peptide unit selected from a glyicine and four adjacent sarcosines. In some cases, K1includes 2 glycines and 8 sarcosines. In some cases, K1includes 3 glycines and 8 sarcosines. In some cases, K1includes 4 glycines and 7 sarcosines. In some cases, K1includes 3 glycines and 7 sarcosines. In some cases, K1includes 3 glycines and 6 sarcosines. In some cases, K1includes 3 glycines and 5 sarcosines. In some cases, K1includes 3 glycines and 4 sarcosines. In some cases, K1includes 3 glycines and 3 sarcosines. In some cases, K1includes 3 glycines and 9 sarcosines. In some cases, K1includes 3 glycines and 10 sarcosines. In some cases, K1includes 5 glycines and 5 sarcosines. In some cases, K1includes 4 glycines and 4 sarcosines. In some cases, K1includes 4 glycines and 5 sarcosines. In some cases, K1includes 5 glycines and 4 sarcosines. In some cases, K1has at most 9 sarcosines. In some cases, K1has at most 8 sarcosines. In some cases, K1has at most 7 sarcosines. In some cases, K1has at most 6 sarcosines. In some cases, K1has at most 5 sarcosines. In some cases, K1has at most 4 sarcosines. In some cases, K1has at most 3 sarcosines. In some cases, K1has at most 2 sarcosines. In some cases, K1has at most 1sarcosine. In some cases, K1has at most 9 glycines. In some cases, K1has at most 8 glycines. In some cases, K1has at most 7 glycines. In some cases, K1has at most 6 glycines. In some cases, K1has at most 5 glycines. In some cases, K1has at most 4 glycines. In some cases, K1has at most 3 glycines. In some cases, K1has at most 2 glycines. In some cases, K1has at most 1 glycine. In some cases, the amino acids of K1are 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 K1are 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 K1are 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 K1are selected from a group consisting of glycine, sarcosine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of K1is selected from a group consisting of glycine, proline, serine, alanine, and β -Alanine. In some cases, the amino acids of K1are selected from a group consisting of proline, serine, alanine, and β-Alanine. In some cases, the amino acids of K1includes at least one glycine and at least one other amino acid. In some cases, the amino acids of K1includes at least one glycine and at least one sarcosine. In some cases, the amino acids of K1includes 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 K1are selected from a group consisting of glycine, proline, serine, alanine, and β - Alanine. In some cases, K1includes at least one glycine. In some cases, K1includes at least one proline. In some cases, K1includes at least one serine. In some cases, K1includes at least one alanine. In some cases, K1includes at least one β-Alanine.

[0217] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each K1independently includes 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, each K1independently includes 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, each K1independently includes PASylation of lessthan PAS50. In some cases, each K1independently includes PASylation of less than PAS25. In some cases, each K1independently includes PASylation of more than PAS5. In some cases, each K1independently includes PASylation of more than PAS9. In some cases, each K1independently includes PASylation of more than PAS15. In some cases, each K1independently includes PASylation of PAS5 to PAS25. In some cases, each K1independently includes PASylation of PAS10 to PAS20. In some cases, each K1independently includes PASylation of PAS10. In some cases, each K1independently includes PASylation of PAS20. In some cases, each K1independently includes a beta-alanine that links the 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 witho ut generating secondary structures. In some cases, PASylation is

[0218] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), K1includes 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, K1includes 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, K1includes PASylation of less than PAS50. In some cases, K1includes PASylation of less than PAS25. In some cases, K1includes PASylation of more than PAS5. In some cases, K1includes PASylation of more than PAS9. In some cases, K1includes PASylation of more than PAS15. In some cases, K1includes PASylation of PAS5 to PAS25. In some cases, K1includesPASylation of PAS10 to PAS20. In some cases, K1includes PASylation of PAS10. In some cases, K1includes PASylation of PAS20. In some cases, K1includes a beta-alanine that links the 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 is

[0219] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each K1is independently selected from. In some cases, each K1is independently selected fromIn some cases, each K1is independently selected fromIn some cases, each K1is independently selected from. In some cases, each K1is independently selected fromIn 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.

[0220] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), K1is selected from,In somecases, 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.

[0221] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), the peptide unit of each K1independently has a terminus unit. In some cases, each K1is independently selected from, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, each K1is independently selected from,, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30.In some cases, each K1is 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 -OR7and -NHR7, 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 -OH, -NH2, and. In some cases, each R6is independently selected from -OH and -NH2. In some cases, each R6is -OH. In some cases, each R6is -NH2. In some cases, each R6is

[0222] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), the peptide unit of K1has a terminus unit. In some cases, K1is selected from, wherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, K1is selected fromwherein the terminus unit is represented by R6, and each j is selected from 1 to 30. In some cases, each K1is independently selected fromwherein 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, R6is selected from -OR7and -NHR7, 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, C3-10carbocycle and 3- to 10-membered heterocycle. 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.

[0223] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each K1is independently selected fromcases, each K1is independently selected fromIn some cases, each K1is independently selected fromcases, each K1is independently selected from ,. In some cases, each K1is independently selected from.

[0224] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), K1is selected from, , , ,,In some cases, K1is selected fromIn somesome cases, K1isIn some cases, K1is

[0225] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), each K1is independently 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 isIn some cases, each K1is independently selected from: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 some cases, each K1is independentlyselected fromIn some cases, each S2isIn some cases, each S2-K1is

[0226] In some embodiments, for a Drug-Linker or salt of Formula (X), Formula (X-D), Formula (X-D-I), Formula (X-D-II), Formula (X-M), Formula (X-M-I), or Formula (X-M-II), or for a conjugate or salt of Formula (XX), Formula (XX-D), Formula (XX-D-I), Formula (XX-D- II), Formula (XX-M), Formula (XX-M-I), or Formula (XX-M-II), K1is 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, K1is selected from, 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 some cases, K1is selected fromIn some cases, S2isIn some cases, S2-K1is

[0227] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each K2is independently selected from KBand KL. In some cases, each K2is independently selected from KB. In some cases, each KBis independently 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 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, each KBis independently 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, each KBis independently 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, each KBis independently selected from a peptide unit,, , In some cases, each KBis independently selected fromIn some cases, each peptide unit is independently a residue.

[0228] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), K2is selected from KBand KL. In some cases, K2is 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 selected from a peptide unit,andIn some cases, KBis selected fromandIn some cases, the peptide unit is a residue.

[0229] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each K2is independently selected from KBand KL. In some cases, each K2is independently selected from KL. In some cases, each KLisindependently 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 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, each KLis independently 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, each KLis independently 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, each KLis independently selected from a peptide unit,In some cases, each KL is independentlyselected from a peptide unit. In some cases, each peptide unit is independently a residue.

[0230] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), K2is selected from KBand KL. In some cases, K2is selected from KL. In some cases, KLis 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, 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 selected from a peptide unit,. In some cases, KLis selected from a peptide unit, In some cases, the peptide unit is a residue.

[0231] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each K2is independently selected from KBand KL. In some cases, each K2is independently selected from KB. In some cases, the peptide unit of each KBindependently has 1 to 50 amino acids. In some cases, the peptide unit of each KBindependently has 1 to 20 amino acids. In some cases, the peptide unit of each KBindependently has 1 to 10 amino acids. In some cases, the peptide unit of each KBindependently has 2 to 50 amino acids. In some cases, the peptide unit of each KBindependently has 2 to 40 amino acids. In some cases, the peptide unit of each KBindependently has 2 to 30 amino acids. In some cases, the peptide unit of each KBindependently has 2 to 20 amino acids. In some cases, the peptide unit of each KBindependently has 2 to 10 amino acids. In some cases, the peptide unit of each KBindependently has 5 to 10 amino acids. In some cases, the peptide unit of each KBindependently has at least 1 amino acid. In some cases, the peptide unit of each KBindependently has 1 amino acid. In some cases, the peptide unit of each KBindependently has at least 2 amino acids. In some cases, the peptide unit of each KBindependently has at least 5 amino acids. In some cases, the peptide unit of each KBindependently has at least 8 amino acids. In some cases, the peptide unit of each KBindependently has at least 10 amino acids. In some cases, the peptide unit of each KBindependently has at most 10 amino acids. In some cases, the peptide unit of each KBindependently has 10 amino acids. In some cases, the peptide unit of each KBindependently has at least 12 amino acids. In some cases, the peptide unit of each KBindependently has at most 12 amino acids. In some cases, the peptide unit of each KBindependently has at least 20 amino acids. In some cases, the peptide unit of each KBindependently has at most 20 amino acids. In some cases, the peptide unit of each KBindependently has 20 amino acids. In some cases, the peptide unit of each KBindependently has at most 30 amino acids. In some cases, the peptide unit of each KBindependently has at least 30 amino acids. In some cases, the amino acids of each KBare independently 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, theamino acids of each KBare independently 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 each KBare independently 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 each KBare independently selected from a group consisting of glycine, sarcosine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of each KBare independently selected from a group consisting of glycine, proline, serine, alanine, and β - Alanine. In some cases, the amino acids of each KBindependently are selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, each KBindependently includes at least one glycine. In some cases, each KBindependently includes at least one proline. In some cases, each KBindependently includes at least one serine. In some cases, each KBindependently includes at least one alanine. In some cases, each KBindependently includes at least one β-Alanine. In some cases, each KBis independently a polysarcosine. In some cases, each KBis independently a polysarcosine with ten repeating sarcosine units.

[0232] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), K2is selected from KBand KL. In some cases, K2is 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, the peptide unit of KBhas at least 12amino 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, 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 acids of KBare selected from a group consisting of glycine, sarcosine, 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, 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.

[0233] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each K2is independently selected from KBand KL. In some cases, each K2is independently selected from KL. In some cases, the peptide unit of each KLindependently has 1 to 50 amino acids. In some cases, the peptide unit of each KLindependently has 1 to 20 amino acids. In some cases, the peptide unit of each KLindependently has 1 to 10 amino acids. In some cases, the peptide unit of each KLindependently has 2 to 50 amino acids. In some cases, the peptide unit of each KLindependently has 2 to 40 amino acids. In some cases, the peptide unit of each KLindependently has 2 to 30 amino acids. In some cases, the peptide unit of each KLindependently has 2 to 20 amino acids. In some cases, the peptide unit of each KLindependently has 2 to 10 amino acids. In some cases, the peptide unit of eachKLindependently has 5 to 10 amino acids. In some cases, the peptide unit of each KLindependently has at least 1 amino acid. In some cases, the peptide unit of each KLindependently has 1 amino acid. In some cases, the peptide unit of each KLindependently has at least 2 amino acids. In some cases, the peptide unit of each KLindependently has at least 5 amino acids. In some cases, the peptide unit of each KLindependently has at least 8 amino acids. In some cases, the peptide unit of each KLindependently has at least 10 amino acids. In some cases, the peptide unit of each KLindependently has at most 10 amino acids. In some cases, the peptide unit of each KLindependently has 10 amino acids. In some cases, the peptide unit of each KLindependently has at least 12 amino acids. In some cases, the peptide unit of each KLindependently has at most 12 amino acids. In some cases, the peptide unit of each KLindependently has at least 20 amino acids. In some cases, the peptide unit of each KLindependently has at most 20 amino acids. In some cases, the peptide unit of each KLindependently has 20 amino acids. In some cases, the peptide unit of each KLindependently has at most 30 amino acids. In some cases, the peptide unit of each KLindependently has at least 30 amino acids. In some cases, the amino acids of each KLare independently 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 each KLare independently 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 each KLare independently 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 each KLare independently selected from a group consisting of glycine, sarcosine, proline, serine, alanine, and β-Alanine. In some cases, the amino acids of each KLare independently selected from a group consisting of glycine, proline, serine, alanine, and β- Alanine. In some cases, the amino acids of each KLindependently are selected from a group consisting of glycine, proline, serine, alanine, and β-Alanine. In some cases, each KLindependently includes at least one glycine. In some cases, each KLindependently includes at least one proline. In some cases, each KLindependently includes at least one serine. In some cases, each KLindependently includes at least one alanine. In some cases, each KLindependently includes at least one β-Alanine. In some cases, each KLis independently a polysarcosine. In some cases, each KLis independently a polysarcosine with ten repeating sarcosine units.

[0234] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), K2is selected from KBand KL. In some cases, K2is 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, 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 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.

[0235] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each K2is independently selected from KBand KL. In some cases, each K2is independently selected from KB. In some cases, each KBis independently selected from a peptide unit, wherein the peptide unit has a terminal -NH2. In some cases, each KBindependently is selected from a peptide unit, wherein the peptide unit has a terminal -OH. In some cases, each KBindependently is selected from a peptide unit, wherein the peptide unit has a terminalIn some cases, each KBindependently is selected from a peptide unit, wherein the peptide unit has a terminal. In some cases, each KBindependently is selected from a peptide, wherein the peptide has a terminal -NH2. In some cases, each KBindependently is selected from a peptide, wherein the peptide has a terminal -OH. In some cases, each KBindependently is selected from a peptide, wherein the peptide has a terminal. In some cases, each KBindependently is selected from a peptide, wherein the peptide has a terminal

[0236] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), K2is selected from KBand KL. In some cases, K2is 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 unithas a terminal. In some cases, KBis selected from a peptide unit, wherein the peptide unit has a terminalIn 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 terminalIn some cases, KBis selected from a peptide, wherein the peptide has a terminal.

[0237] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT-M-II), each K2is independently selected from KBand KL. In some cases, each K2is independently selected from KL. In some cases, each KLis independently selected from a peptide unit, wherein the peptide unit has a terminal -NH2. In some cases, each KLindependently is selected from a peptide unit, wherein the peptide unit has a terminal -OH. In some cases, each KLindependently is selected from a peptide unit, wherein the peptide unit has a terminalIn some cases, each KLindependently is selected from a peptide unit, wherein the peptide unit has a terminal. In some cases, each KLindependently is selected from a peptide, wherein the peptide has a terminal -NH2. In some cases, each KLindependently is selected from a peptide, wherein the peptide has a terminal -OH. In some cases, each KLindependently is selected from a peptide, wherein the peptide has aterminal. In some cases, each KLindependently is selected from a peptide, wherein the peptide has a terminal

[0238] In some embodiments, for a Drug-Linker or salt of Formula (X*), Formula (XT), Formula (XT-D), Formula (XT-D-I), Formula (XT-D-II), Formula (XT-M), Formula (X-M-I) or Formula (XT-M-II), or for a conjugate or salt of Formula (XXX*), Formula (XX*), Formula (XXT), Formula (XXT-D), Formula (XXT-D-I), Formula (XXT-D-II), Formula (XXT-M), Formula (XXT-M-I), or Formula (XXT...

Claims

1. CLAIMS WHAT IS CLAIMED IS:

1. A Drug-Linker of Formula (X*):or a pharmaceutically acceptable salt thereof, wherein; each D is independently a Drug unit; each Y1is independently absent or independently selected from -O-T1and -NH-T2; each T1is independently a sugar cleavable unit; each T2is independently a peptide cleavable unit; each S1is independently 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, and –P(O)(R20)2–; each S2is independently 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–; S3is 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–; each S4is independently absent or independently 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–; J is 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, S4, and J, 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 click group wherein the click group comprises at least one click handle selected from azidyl, alkynyl, and alkynylene; each K1is independently selected from: (i) a peptide unit, (ii) an oligosaccharide; and (iii) a polyether; each K2is independently selected from KBand KL; each KBis independently 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 KLis independently 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; 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; z is selected from 0 and 1; and each w is independently selected from 0 and 1 and each v is independently selected from 0 and 1, provided that: when at least one w is 1, then each v is 0 and when at least one v is selected 1, then each w is 0.

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

3. The Drug-Linker or salt of claim 1, wherein Formula (X*) or Formula (X) is represented by the structure of Formula (X-D):or a pharmaceutically acceptable salt thereof.

4. The Drug-Linker or salt of any one of claims 1 to 3, wherein S3is5. The Drug-Linker or salt of any one of claims 1 to 4, wherein S3is6. The Drug-Linker or salt of any one of claims 1 to 5, wherein J is selected from C8-C30alkylene wherein one or more alkylene units of the alkylene are independently replaced by – N(R20)–, and –O–.

7. The Drug-Linker or salt of any one of claims 1 to 6, wherein J is selected from8. The Drug-Linker or salt of any one of claims 1 to 7, wherein J is9. The Drug-Linker or salt of any one of claims 1 to 8, wherein J-S3is10. The Drug-Linker or salt of any one of claims 1 to 9, wherein each S1is independently 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)–.

11. The Drug-Linker or salt of any one of claims 1 to 10, wherein each S1is independently selected from12. The Drug-Linker or salt of any one of claims 1 to 11, wherein each S1-S2-K1is independently selected from.

13. The Drug-Linker or salt of any one of claims 1 to 12, whereinis selected from.

14. The Drug-Linker or salt of any one of claims 1 to 13, wherein each S2is.

15. The Drug-Linker or salt of any one of claims 1 to 14, whereinis selected from.

16. The Drug-Linker or salt of any one of claims 1 to 15, wherein K1is a peptide unit.

17. The Drug-Linker or salt of claim 16, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

18. The Drug-Linker or salt of claim 16 or claim 17, wherein the peptide unit has a terminus unit represented by R6, wherein R6is selected from -OH, -NH2, and.

19. The Drug-Linker or salt of any one of claims 1 to 18, wherein each K1is independently selected from.

20. The Drug-Linker or salt of claim 1, wherein Formula (X*) or Formula (X) is represented by the structure of Formula (X-M):or a pharmaceutically acceptable salt thereof.

21. The Drug-Linker or salt of any one of claims 1 to 2, or 20, wherein S3is22. The Drug-Linker or salt of claim 21, wherein S3is23. The Drug-Linker or salt of claim 20 or claim 21, wherein J is selected from C5-C18alkylene wherein one or more alkylene units of the alkylene are independently replaced by N(R20)-, and -O-.

24. The Drug-Linker or salt of any one of claims 20 to 23, wherein J is25. The Drug-Linker or salt of any one of claims 20 to 24, wherein J is26. The Drug-Linker or salt of any one of claims 20 to 25, wherein J-S3is27. The Drug-Linker or salt of any one of claims 20 to 26, wherein each S1is independently 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)-.

28. The Drug-Linker or salt of any one of claims 20 to 27, wherein each S1is independently selected from29. The Drug-Linker or salt of any one of claims 20 to 28, wherein S1-S2-K1is selected from30. The Drug-Linker or salt of any one of claims 20 to 29, whereinis selected from31. The Drug-Linker or salt of any one of claims 20 to 30, wherein S2is.

32. The Drug-Linker or salt of any one of claims 20 to 31, whereinselected from33. The Drug-Linker or salt of any one of claims 20 to 32, wherein K1is a peptide unit.

34. The Drug-Linker or salt of any one of claims 20 to 33, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

35. The Drug-Linker or salt of any one of claims 20 to 34, wherein the peptide unit has a terminus unit represented by R6, wherein R6is selected from -OH, -NH2, and.

36. The Drug-Linker or salt of any one of claims 20 to 35, wherein K1is selected from ,,.

37. The Drug-Linker or salt of any one of claims 20 to 36, wherein Y1is.

38. The Drug-Linker or salt of any one of claims 20 to 36, wherein Y1is39. The Drug-Linker or salt of claim 1, wherein Formula (X*) is represented by the structure of Formula (XT):or a pharmaceutically acceptable salt thereof.

40. The Drug-Linker or salt of claims 1 or 39, wherein Formula (X*) or Formula (XT) is represented by the structure of Formula (XT-D):or a pharmaceutically acceptable salt thereof.

41. The Drug-Linker or salt of claim 39 or claim 40, wherein S3is42. The Drug-Linker or salt of any one of claims 39 to 41, wherein S3is.

43. The Drug-Linker or salt of any one of claims 39 to 42, wherein J is selected from C8-C30alkylene wherein one or more alkylene units of the alkylene are independently replaced by – N(R20)–, and –O–.

44. The Drug-Linker or salt of any one of claims 39 to 43, wherein J is selected from.

45. The Drug-Linker or salt of any one of claims 39 to 44, wherein J is.

46. The Drug-Linker or salt of any one of claims 39 to 45, wherein J-S3is selected from.

47. The Drug-Linker or salt of any one of claims 39 to 46, wherein.

48. The Drug-Linker or salt of any one of claims 1, or 39 to 47, wherein each Y1-S4-K2is independently selected from49. The Drug-Linker or salt of any one of claim 48, wherein each S4is50. The Drug-Linker or salt of claim 48 or claim 49, wherein each Y1-S4-K2is independently selected from51. The Drug-Linker or salt of any one of claims 48 to 50, wherein KBis a peptide unit.

52. The Drug-Linker or salt of any one of claims 48 to 51, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

53. The Drug-Linker or salt of any one of claims 48 to 52, wherein the peptide unit has a terminus unit represented by R6, wherein R6is selected from -OH, -NH2, and.

54. The Drug-Linker or salt of any one of claims 48 to 53, wherein each KBis independently selected from ,,.

55. The Drug-Linker or salt of any one of claims 39 to 54, wherein each Y1-S4-K2is independently selected fromand.

56. The Drug-Linker or salt of any one of claim 48, wherein each S4is.

57. The Drug-Linker or salt of any one of claims 51, wherein each Y1-S4-K2is independently selected from.

58. The Drug-Linker or salt of claim 53 or claim 54, wherein each KBis independently selected from59. The Drug-Linker or salt of any one of claims 53 to 55, wherein each Y1-S4-K2is independently selected from,60. The Drug-Linker or salt of any one of claims 1, or 39 to 47, wherein each Y1-S4-K2is independently selected from.

61. The Drug-Linker or salt of claim 60, wherein each S4is absent.

62. The Drug-Linker or salt of claim 60 or claim 61, wherein KLis a peptide unit.

63. The Drug-Linker or salt of any one of claims 60 to 62, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

64. The Drug-Linker or salt of any one of claims 60 to 63, wherein the peptide unit has a capping moiety, wherein the capping moiety is65. The Drug-Linker or salt of any one of claims 60 to 64, wherein each KLis independently selected from.

66. The Drug-Linker or salt of any one of claims 39 to 47, or 60 to 64, wherein each Y1-S4- K2is independently selected from,.

67. The Drug-Linker or salt of claim 60, wherein each S4is.

68. The Drug-Linker or salt of claim 67, wherein each S4is.

69. The Drug-Linker or salt of claims 67 or 68, wherein each Y1-S4-K2is independently selected from70. The Drug-Linker or salt of any one of claims 67 to 69, wherein KLis a peptide unit.

71. The Drug-Linker or salt of any one of claims 67 to 70, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

72. The Drug-Linker or salt of any one of claims 67 to 71, wherein the peptide unit has a terminus unit represented by R6, wherein R6is selected from -OH, and -NH2.

73. The Drug-Linker or salt of any one of claims 67 to 72, wherein each KLis independently selected from74. The Drug-Linker or salt of any one of claims 67 to 73, wherein each Y1-S4-K2is independently selected from.

75. The Drug-Linker or salt of claim 1, wherein Formula (X*) or Formula (XT) is represented by the structure of Formula (XT-M):or a pharmaceutically acceptable salt thereof.

76. The Drug-Linker or salt of claim 75, wherein S3is77. The Drug-Linker or salt of claim 76, wherein S3is78. The Drug-Linker or salt of any one of claims 75 to 77, wherein J is selected from C5-C18alkylene wherein one or more alkylene units of the alkylene are independently replaced by – N(R20)–, and –O–.

79. The Drug-Linker or salt of any one of claims 75 to 78, wherein J is80. The Drug-Linker or salt of any one of 75 to 79, wherein J is.

81. The Drug-Linker or salt of any one of claims 75 to 80, wherein J-S3is82. The Drug-Linker or salt of any one of claims 75 to 81, wherein each S1is independently 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)–.

83. The Drug-Linker or salt of any one of claims 75 to 82, wherein each S1is independently selected from84. The Drug-Linker or salt of any one of claims 75 to 83, wherein85. The Drug-Linker or salt of any one of claims 75 to 84, wherein Y1-S4-K2is selected from.

86. The Drug-Linker or salt of any one of claims 75 to 85, wherein S4is87. The Drug-Linker or salt of any one of claims 75 to 86, wherein Y1-S4-K2is selected from.

88. The Drug-Linker or salt of any one of claims 85 to 87, wherein KBis a peptide unit.

89. The Drug-Linker or salt of any one of claims 85 to 88, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

90. The Drug-Linker or salt of any one of claims 85 to 89, wherein the peptide unit has a terminus unit represented by R6, wherein R6is selected from -OH, -NH2, and.

91. The Drug-Linker or salt of any one of claims 85 to 90, wherein KBis selected from ,92. The Drug-Linker or salt of any one of claims 75 to 91, wherein Y1-S4-K2is selected from93. The Drug-Linker or salt of claim 85, wherein S4is94. The Drug-Linker or salt of claim 93, wherein Y1-S4-K2is selected from.

95. The Drug-Linker or salt of claim 94, wherein KBis selected from96. The Drug-Linker or salt of any one of claims 93 to 95, wherein Y1-S4-K2is selected from.

97. The Drug-Linker or salt of any one of claims 75 to 84, wherein Y1-S4-K2is selected from.

98. The Drug-Linker or salt of claim 97, wherein S4is absent.

99. The Drug-Linker or salt of claim 97 or claim 98, wherein KLis a peptide unit.

100. The Drug-Linker or salt of any one of claims 97 to 99, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine proline, and serine.

101. The Drug-Linker or salt of any one of claims 97 to 100, wherein the peptide unit has a capping moiety, wherein the capping moiety is.

102. The Drug-Linker or salt of any one of claims 97 to 101, wherein KLis selected from.

103. The Drug-Linker or salt of any one of claims 97 to 102, wherein Y1-S4-K2is selected,.

104. The Drug-Linker or salt of claim 82, wherein S4is.

105. The Drug-Linker or salt of claim 86, wherein S4is.

106. The Drug-Linker or salt of claim 87, wherein Y1-S4-K2is selected from.

107. The Drug-Linker or salt of any one of claims 104 to 106, wherein KLis a peptide unit.

108. The Drug-Linker or salt of any one of claims 104 to 107, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

109. The Drug-Linker or salt of any one of claims 104 to 108, wherein the peptide unit has a terminus unit represented by R6, wherein R6is selected from -OH, -NH2, and110. The Drug-Linker or salt of any one of claims 104 to 109, wherein KLis selected from111. The Drug-Linker or salt of any one of claims 104 to 110, wherein Y1-S4-K2is selected from,112. The Drug-Linker or salt of any one of claims 1 to 111, wherein D is selected from113. The Drug-Linker or salt of any one of claims 1 to 112, wherein D is selected from114. The Drug-Linker or salt of any one of claims 1 to 113, wherein D is selected from.

115. The Drug-Linker or salt of any one of claims 1 to 113, wherein D is selected from116. The Drug-Linker or salt of any one of claims 1 to 115, wherein M1is117. A Conjugate of Formula (XX*):or a pharmaceutically acceptable salt thereof, wherein; each D is independently a Drug unit; each Y1is independently absent or independently selected from -O-T1and -NH-T2; each T1is independently a sugar cleavable unit; each T2is independently a peptide cleavable unit;L is a Targeting unit; each S1is independently 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–; each S2is independently 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–; S3is 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–; each S4is independently absent or independently 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, S4, and L, 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; M2is a connector unit formed from a click group; each K1is independently selected from:(i) a peptide unit, (ii) an oligosaccharide; and (iii) a polyether; each K2is independently selected from KBand KL; each KBis independently 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 KLis independently 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; 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; z is selected from 0 and 1; and each w is independently selected from 0 and 1 and each v is independently selected from 0 and 1, provided that:when at least one w is 1, then each v is 0 and when at least one v is selected 1, then each w is 0.

118. The Conjugate or salt of claim 117, wherein Formula (XX*) is represented by the structure of Formula (XX):or a pharmaceutically acceptable salt thereof .

119. The Conjugate or salt of claims 117 or 118, wherein Formula (XX*) or Formula (XX) is represented by the structure of Formula (XX-D):or a pharmaceutically acceptable salt thereof.

120. The Conjugate or salt of any one of claims 117 to 119, wherein S3is121. The Conjugate or salt of any one of claims 117 to 120, wherein S3is.

122. The Conjugate or salt of any one of claims 117 to 121, wherein J is selected from C8-C30alkylene wherein one or more alkylene units of the alkylene are independently replaced by – N(R20)–, and –O–.

123. The Conjugate or salt of any one of claims 117 to 122, wherein J is selected from.

124. The Conjugate or salt of any one of claims 117 to 123, wherein J is125. The Conjugate or salt of any one of claims 117 to 124, wherein J-S3is.

126. The Conjugate or salt of any one of claims 117 to 125, wherein each S1is independently 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)–.

127. The Conjugate or salt of any one of claims 117 to 126, wherein each S1is independently selected from.

128. The Conjugate or salt of any one of claims 117 to 127, wherein each S1-S2-K1is independently selected from.

129. The Conjugate or salt of any one of claims 117 to 128, whereinis selected from.

130. The Conjugate or salt of any one of claims 117 to 129, wherein each S2is .

131. The Conjugate or salt of any one of claims 117 to 130, whereinis selected from.

132. The Conjugate or salt of any one of claims 117 to 131, wherein K1is a peptide unit.

133. The Conjugate or salt of claim 132, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

134. The Conjugate or salt of any one of claims 117 to 133, wherein the peptide unit has a terminus unit represented by R6, wherein R6is selected from -OH, -NH2, and.

135. The Conjugate or salt of any one of claims 117 to 134, wherein each K1is independently selected from136. The Conjugate or salt of claim 117, wherein Formula (XX) is represented by the structure of Formula (XX-M):or a pharmaceutically acceptable salt thereof.

137. The Conjugate or salt of claim 136, wherein S3is138. The Conjugate or salt of claim 136 or claim 137, wherein S3is139. The Conjugate or salt of any one of claims 136 to 138, wherein J is selected from C5-C18alkylene wherein one or more alkylene units of the alkylene are independently replaced by – N(R20)–, and –O–.

140. The Conjugate or salt of any one of claims 136 to 139, wherein J is.

141. The Conjugate or salt of any one of claims 136 to 140, wherein J is142. The Conjugate or salt of any one of claims 136 to 141, wherein J-S3is143. The Conjugate or salt of any one of claims 136 to 142, wherein each S1is independently 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)–.

144. The Conjugate or salt of any one of claims 136 to 143, wherein each S1is independently selected from.

145. The Conjugate or salt of any one of claims 136 to 144, wherein S1-S2-K1is selected from.

146. The Conjugate or salt of any one of claims 136 to 145, whereinis selected from147. The Conjugate or salt of any one of claims 136 to 146, wherein S2is148. The Conjugate or salt of any one of claims 136 to 147, whereinisselected from149. The Conjugate or salt of any one of claims 136 to 148, wherein K1is a peptide unit.

150. The Conjugate or salt of claim 149, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

151. The Conjugate or salt of any one of claims 136 to 150, wherein the peptide unit has a terminus unit represented by R6, wherein R6is selected from -OH, -NH2, and152. The Conjugate or salt of any one of claims 136 to 151 , wherein K1is selected from,.

153. The Conjugate or salt of any one of claims 136 to 152, wherein Y1is.

154. The Conjugate or salt of any one of claims 136 to 152, wherein Y1is155. The Conjugate or salt of claim 136, wherein Formula (XX*) is represented by the structure of Formula (XXT):or a pharmaceutically acceptable salt thereof .

156. The Conjugate or salt of claims 136 or 155, wherein Formula (XX*) or Formula (XXT) is represented by the structure of Formula (XXT-D):or a pharmaceutically acceptable salt thereof.

157. The Conjugate or salt of any one of claims 155 to 156, wherein S3is158. The Conjugate or salt of any one of claims 155 to 157, wherein S3is.

159. The Conjugate or salt of any one of claims 155 to 158, wherein J is selected from C8-C30alkylene wherein one or more alkylene units of the alkylene are independently replaced by – N(R20)–, and –O–.

160. The Conjugate or salt of any one of claims 155 to 159, wherein J is selected from.

161. The Conjugate or salt of any one of claims 155 to 160, wherein J is162. The Conjugate or salt of any one of claims 155 to 161, wherein J-S3is.

163. The Conjugate or salt of any one of claims 155 to 162, wherein.

164. The Conjugate or salt of any one of claims 155 to 163, wherein each Y1-S4-K2is independently selected from.

165. The Conjugate or salt of any one of claims 155 to 164, wherein each S4is.

166. The Conjugate or salt of any one of claims 155 to 165, wherein each Y1-S4-K2is independently selected from.

167. The Conjugate or salt of any one of claims 164 to 166, wherein KBis a peptide unit.

168. The Conjugate or salt of any one of claims 164 to 167, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

169. The Conjugate or salt of claim 167 or claim 168, wherein the peptide unit has a terminus unit represented by R6, wherein R6is selected from -OH, -NH2, and170. The Conjugate or salt of any one of claims 164 to 169, wherein each KBis independently selected from,.

171. The Conjugate or salt of any one of claims 164 to 170, wherein each Y1-S4-K2is independently selected from,.

172. The Conjugate or salt of claim 164, wherein each S4is.

173. The Conjugate or salt of claim 172, wherein each Y1-S4-K2is independently selected from.

174. The Conjugate or salt of claim 173, wherein each KBis independently selected from175. The Conjugate or salt of any one of claims 172 to 174, wherein each Y1-S4-K2is independently selected from,176. The Conjugate or salt of any one of claims 155 to 163, wherein each Y1-S4-K2is independently selected from.

177. The Conjugate or salt of claim 176, wherein each S4is absent.

178. The Conjugate or salt of claim 176 or claim 177, wherein KLis a peptide unit.

179. The Conjugate or salt of claim 178, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

180. The Conjugate or salt of any one of claims 176 to 179, wherein the peptide unit has a capping moiety, wherein the capping moiety is.

181. The Conjugate or salt of any one of claims 176 to 180, wherein each KLis independently selected from182. The Conjugate or salt of any one of claims 176 to 181, wherein each YJ-S4-K2is independently selected from183. The Conjugate or salt of claim 176, wherein each S4iso o184. The Conjugate or salt of claim 183, wherein each S4is185. The Conjugate or salt of claim 183 or claim 184, wherein each Y1-S4-K2is independently selected from.

186. The Conjugate or salt of claim 185, wherein KLis a peptide unit.

187. The Conjugate or salt of claim 186, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine proline, and serine.

188. The Conjugate or salt of claim 186 or claim 187, wherein the peptide unit has a terminus unit represented by R6, wherein R6is selected from -OH, and -NH2.

189. The Conjugate or salt of any one of claims 185 to 188, wherein each KLis independently selected from190. The Conjugate or salt of any one of claims 185 to 188, wherein each Y1-S4-K2is independently selected from.

191. The Conjugate or salt of claim 117, wherein Formula (XX*) or Formula (XXT) is represented by the structure of Formula (XXT-M):or a pharmaceutically acceptable salt thereof.

192. The Conjugate or salt of claim 191, wherein S3is193. The Conjugate or salt of claim 192, wherein S3is194. The Conjugate or salt of any one of claims 190 to 193, wherein J is selected from C5-C18alkylene wherein one or more alkylene units of the alkylene are independently replaced by – N(R20)–, and –O–.

195. The Conjugate or salt of any one of claims 191 to 194, wherein J is196. The Conjugate or salt of any one of claims 190 to 195, wherein J is197. The Conjugate or salt of any one of claims 191 to 196, wherein J-S3is198. The Conjugate or salt of any one of claims 191 to 197, wherein each S1is independently 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)–.

199. The Conjugate or salt of any one of claims 191 to 198, wherein each S1is independently selected from200. The Conjugate or salt of any one of claims 191 to 199, whereinis.

201. The Conjugate or salt of any one of claims 191 to 200, wherein Y1-S4-K2is selected from.

202. The Conjugate or salt of any one of claims 191 to 201, wherein S4is.

203. The Conjugate or salt of any one of claims 191 to 202, wherein Y1-S4-K2is selected from.

204. The Conjugate or salt of claim 203, wherein each KBis a peptide unit.

205. The Conjugate or salt of claim 204, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

206. The Conjugate or salt of claim 205, wherein the peptide unit has a terminus unit represented by R6, wherein R6is selected from -OH, -NH2, and.

207. The Conjugate or salt of any one of claims 191 to 206, wherein KBis selected from, and208. The Conjugate or salt of any one of claims 191 to 207, wherein Y1-S4-K2is selected from209. The Conjugate or salt of claim 201, wherein S4is210. The Conjugate or salt of claim 209, wherein Y1-S4-K2is selected from.

211. The Conjugate or salt of claim 209 or claim 210, wherein KBis selected from212. The Conjugate or salt of any one of claims 209 to 211, wherein Y1-S4-K2is selected from.

213. The Conjugate or salt of any one of claims 191 to 200, wherein Y1-S4-K2is selected from.

214. The Conjugate or salt of claim 213, wherein S4is absent.

215. The Conjugate or salt of claim 213 or claim 214, wherein KLis a peptide unit.

216. The Conjugate or salt of claim 215, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine proline, and serine.

217. The Conjugate or salt of any one of claims 213 to 216, wherein the peptide unit has a capping moiety, wherein the capping moiety is218. The Conjugate or salt of any one of claims 213 to 217, wherein KLis selected from219. The Conjugate or salt of any one of claims 213 to 218, wherein Y1-S4-K2is selected from.

220. The Conjugate or salt of claim 213, wherein S4is221. The Conjugate or salt of claim 220, wherein Y1-S4-K2is selected from.

222. The Conjugate or salt of claim 221, wherein KLis a peptide unit.

223. The Conjugate or salt of claim 222, wherein the peptide unit has one or more amino acids selected from sarcosine, glycine, β-Alanine, alanine, proline, and serine.

224. The Conjugate or salt of any one of claims 221 to 223, wherein the peptide unit has a terminus unit represented by R6, wherein R6is selected from -OH, -NH2, and225. The Conjugate or salt of any one of claims 221 to 224, wherein KLis selected from226. The Conjugate or salt of any one of claims 221 to 225, wherein Y1-S4-K2is selected from, and227. The Conjugate or salt of any one of claims 117 to 226, wherein D is selected from ,228. The Conjugate or salt of any one of claims 117 to 226, wherein D is selected from229. The Conjugate or salt of any one of claims 117 to 226, wherein D is selected from230. The Conjugate or salt of any one of claims 117 to 226, wherein D is selected from.

231. The Conjugate or salt of any one of claims 117 to 230, wherein M2is selected from.

232. The conjugate or salt of any one of claims 117 to 231, wherein the Targeting unit comprises an antibody or an antigen-binding portion thereof.

233. The conjugate of claim 232, wherein the antibody is a monoclonal antibody.

234. The conjugate or salt of claim 232 to claim 233, wherein the Targeting unit further comprises a spacer, wherein the spacer is in between the antibody and M2.

235. The conjugate or salt of any one of claims 117 to 231, having an average ratio of Drug- Linker to Targeting unit (DAR) of about 1 to about 2.

236. The conjugate or salt of any one of claims 117 to 231, having an average ratio of Drug- Linker to Targeting unit (DAR) of about 2.

237. The conjugate or salt of any one of claims 117 to 231, having an average ratio of Drug- Linker to Targeting unit (DAR) of about 1.

238. A Conjugate selected from Table AA-M, Table AA-D, AA-M-TB, AA-D-TB, AA-M- TL, and AA-D-TL.

239. A Conjugate selected from Table AA-M.

240. A Conjugate selected from Table AA-D.

241. A Conjugate selected from Table AA-M-TB.

242. A Conjugate selected from Table AA-D-TB.

243. A Conjugate selected from Table AA-M-TL.

244. A Conjugate selected from Table AA-D-TL.

245. A pharmaceutical composition comprising a conjugate of any one of claims 117 to 244 and a pharmaceutically acceptable excipient.

246. 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 117 to 244 or a pharmaceutical composition of claim 245.

247. The method of claim 246, wherein the disease or disorder is a cancer.

248. A method of treating a subject with a cancer, comprising administering to the subject in need thereof a conjugate of any one of claims 117 to 244 or a pharmaceutical composition of claim 245.

249. A method of treating a subject with a tumor, comprising administering to the subject in need thereof a conjugate of any one of claims 117 to 244 or a pharmaceutical composition of claim 245.

250. The method of claim 249, wherein the tumor is associated with a cancer.

251. 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 117 to 244 or a pharmaceutical composition of claim 245.

252. The use of claim 251, wherein the disease or disorder is a cancer.

253. The method or use of any one of claims 247 to 252, 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; intestinal cancers, particularly colorectal cancer; ovarian cancer; small cell and non -small cell lung cancer (SCLC and NSCLC); breast cancer sarcomas, such as fibrosarcoma, malignant fibrous histiocytoma, embryonal rhabdomyosarcoma, 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.

254. The method of any one of claims 247 to 252, 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, nasopharyngeal cancer, breast cancer (e.g., triple negative breast cancer), lung cancer (e.g., non-small cell lung cancer (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.

255. The method of any one of claims 247 to 252, wherein the cancer is selected from cell lymphoma, non-small cell lung cancer, large-cell lung cancer, breast cancer, and small -cell lung cancer.

256. The method of any one of claims 247 to 252, wherein the cancer is cell lymphoma.

257. The method of any one of claims 247 to 252, wherein the cancer is non-small cell lung cancer.

258. The method of any one of claims 247 to 252, wherein the cancer is large-cell lung cancer.

259. The method of any one of claims 247 to 252, wherein the cancer is breast cancer.

260. The method of any one of claims 247 to 252, wherein the cancer is small-cell lung cancer.

261. A Drug-Linker selected from Table A-M, Table A-D, A-M-TB, A-D-TB, A-M-TL, and A-D-TL.

262. A Drug-Linker selected from Table A-M.

263. A Drug-Linker selected from Table A-D.

264. A Drug-Linker selected from Table A-M-TB.

265. A Drug-Linker selected from Table A-D-TB.

266. A Drug-Linker selected from Table A-M-TL.

267. A Drug-Linker selected from Table A-D-TL.

268. A conjugate of Formula (XXX*):or a pharmaceutically acceptable salt thereof, wherein; p is selected from 1 to 2; each D is independently a Drug unit; each Y1is independently absent or independently selected from -O-T1and -NH-T2; each T1is independently a sugar cleavable unit; each T2is independently a peptide cleavable unit; L is a Targeting unit; B is a Scaffold unit; each S1is independently 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–; each S2is independently 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–; S3is 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–; each S4is independently absent or independently 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, S4, and L, 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; M2is a connector unit formed from a click group; each K1is independently selected from: (i) a peptide unit, (ii) an oligosaccharide; and (iii) a polyether; each K2is independently selected from KBand KL; each KBis independently 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 KLis independently 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; 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; z is selected from 0 and 1; and each w is independently selected from 0 and 1 and each v is independently selected from 0 and 1, provided that: when at least one w is 1, then each v is 0 and when at least one v is selected 1, then each w is 0.

269. The conjugate or salt of claim 268, wherein A1iswherein t represents the connection to the linker and 1, 2, 3, and 4, represent the connection to L; and q is an integer selected from 1 to 8.

270. The conjugate or salt of claim 268, wherein A1iswherein t represents the connection to the linker and 1, 2, 3, and 4, represent the connection to L.

271. The conjugate of any one of claims 268 to 270, wherein L is an antibody or antigen binding portion thereof.

272. The conjugate of any one of claims 268 to 270, wherein L is UC-961.

273. The conjugate or salt of claim 268, wherein A1iswherein t represents a connection to the linker and 1, 2, 3, 4, 5, 6, 7, and 8, represent a connection to L; q is an integer selected from 1 to 8.

274. The conjugate or salt of claim 273, wherein q is 2.

275. The conjugate or salt of claim 273, wherein q is 3.

276. The conjugate or salt of claim 273, wherein q is 4.

277. The conjugate or salt of claim 268, wherein A1iswherein t represents a connection to the linker and 1, 2, 3, 4, 5, 6, 7, and 8, represent a connection to L.

278. The conjugate of any one of claims 273 to 277, wherein L is a VHH fusion Fc.

279. The conjugate of any one of claims 273 to 277, wherein L is an Anti ROR1 VHH fusion Fc.

280. The conjugate or salt of claim 268, wherein the conjugate is selected from Table AAA- M, Table AAA-M-TB, and Table AAA-M-TL.

281. The conjugate or salt of claim 268, wherein the conjugate is selected from Table AAA- M.

282. The conjugate or salt of claim 268, wherein the conjugate is selected from Table AAA- M-TB.

283. The conjugate or salt of claim 268, wherein the conjugate is selected from Table AAA- M-TL.

284. A pharmaceutical composition comprising a conjugate of any one of claims 268 to 283 and a pharmaceutically acceptable excipient.

285. A method of treating a subject with a cancer, comprising administering to the subject in need thereof a conjugate of any one of claims 268 to 283 or a pharmaceutical composition of claim 284.

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