| abstract |
A conjugate having the formula I: A- (L-D) p (I) or a solvate or pharmaceutically acceptable salt thereof, wherein: A is an antibody that selectively binds to FAP (fibroblast activating protein); L is a linker, said linker comprising a spacer comprising - (OCH2CH2) n-, where n = 2 a and where L comprises a linking group for binding to A and a protease cleavable portion comprising a valine-citrulline unit; p is 1 to 10; and D is a drug comprising a cytolysin of formula IV: ** (See formula) ** wherein R2 is H or C1-C4 alkyl; R6 is C1-C6 alkyl; R7 is C1-C6 alkyl, CH2OR19 or CH2OCOR20, where R19 is alkyl, R20 is C2-C6 alkenyl, phenyl or CH2-phenyl; R9 is C1-C6 alkyl; R10 is H, OH, O-alkyl or O-acetyl; f is 1 or 2; R11 has the following structure: ** (See formula) ** where: R21 is H, OH, halogen, NH2, alkyloxy, phenyl, alkylamino or dialkylamino; R16 is H or a C1-C6 alkyl group; R17 is a direct bond to linker L or R17 is C (O) X, CONHNHX, OX, NHX, or SX, where X is a bond to linker L; and q is 0, 1, 2, or 3. |