MC-GGFG-AM- (10Me-11F-Camptothecin)

MC-GGFG-AM- (10Me-11F-Camptothecin) serves as a linker-payload conjugate in the synthesis of ZW251, an antibody-drug conjugate (ADC) targeting human GPC3. ZW251 comprises a humanized IgG1 antibody linked to ZD06519, a novel camptothecin-based topoisomerase 1 inhibitor, through a maleimide-anchor and a cleavable glycyl glycyl phenylalanyl glycine (GGFG) -aminomethyl (AM) linker. ZW251 demonstrates strong affinity for GPC3 in both human and cynomolgus monkey cells, characterized by rapid internalization in GPC3-positive Hepatocellular Carcinoma (HCC) cell lines and induces bystander-mediated killing of GPC3-negative cancer cells [1].

C(NC(OCCOCNC(CNC([C@H](CC1=CC=CC=C1)NC(CNC(CNC(CCCCCN2C(=O)C=CC2=O)=O)=O)=O)=O)=O)=O)C3=C4C(C=5N(C4)C(=O)C6=C(C5)[C@](CC)(O)C(=O)OC6)=NC=7C3=CC(C)=C(F)C7