Cytotoxic and anti-mitotic compounds, and methods of using the same

A conjugate having the following structure:

• (T)-(L)-(PT) (VII)
• wherein (T) is a targeting moiety, wherein the targeting moiety comprises an antibody or an antigen-binding antibody fragment,
• (L) is a linker, and
• (PT) is a hemiasterlin analog, and
• wherein (T)-(L)-(PT) has the following structure:
• wherein:
• R15 is selected from the group consisting of optionally substituted alkyl, optionally substituted alkylamino, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl and optionally substituted heteroaryl;
• R16 and R17 are independently selected from the group consisting of H and C1-6 alkyl;
• R18 and R30 are independently selected from the group consisting of H, C1-6 alkyl and —SH, with the proviso that R18 and R30 cannot both be H;
• R32 is:
• Z is selected from the group consisting of:
• —OH;
• —OR;
• —SH;
• —SR;
• —NH2;
• —NRCH(R11)COOH;
• and —NHCH(R11)COOH, wherein R11 is R or —(CH2)nNR12R13, wherein n=1−4 and R12 and R13 are independently selected from the group consisting of:
• H, R and —C(NH)(NH2);
• R is a saturated or unsaturated linear or branched alkyl containing one to ten carbon atoms, or a cycloalkyl or heterocyclyl containing three to ten carbon atoms and zero to four nitrogen atoms, wherein the carbon atoms are optionally independently substituted with:
• ═O, ═S, OH, —OR10, —O2CR10, —SH, —SR10, —SOCR10, —NH2, —NHR10, —N(R10)2, —NHCOR10, —NR10COR10, —I, —Br, —Cl, —F, —CN, —CO2H, —CO2R10, —CHO, —COR10, —CONH2, —CONHR10, —CON(R10)2, —COSH, —COSR10, —NO2, —SO3H, —SOR10, or —SO2R10, wherein R10 is a linear or branched one to ten carbon saturated or unsaturated alkyl group or a three to ten carbon cycloalkyl;
• Y is a linear, saturated or unsaturated, one to six carbon alkyl group, optionally substituted with R, and
• R14 is selected from the group consisting of optionally substituted alkyl, optionally substituted alkylamino, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl.