Albumin-binding prodrugs of auristatin E derivatives

A compound having the structure of Formula I or II:

• or a pharmaceutically acceptable salt, hydrate, solvate, or isomer thereof;
• wherein:
• R′ is H or —CH3,
• M is H or a pharmaceutically acceptable counterion;
• Y is absent or selected from an optionally substituted C1-C6 alkyl, —NH—C(O)—, —C(O)—NH—, —NH—C(O)—NH—, —C(O)—O—, and —O—C(O)—;
• R1 is absent or an optionally substituted C1-C18 alkyl wherein optionally up to six carbon atoms in said C1-C18 alkyl are each independently replaced with —OCH2CH2—;
• X is H or selected from halogen, —NO2, —NR2R3, —OR2, —NHCOR2 and —OCOR2, wherein R2 and R3 are each independently selected from H and C1-C4 alkyl;
• TBG is a thiol-binding group selected from an optionally substituted maleimide group, an optionally substituted haloacetamide group, an optionally substituted haloacetate group, an optionally substituted pyridylthio group, an optionally substituted isothiocyanate group, an optionally substituted vinylcarbonyl group, an optionally substituted aziridine group, an optionally substituted disulfide group, and an optionally substituted acetylene group.