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

• CAT Number: I041285
• CAS Number: 2873460-70-7
• Molecular Formula: C51H56FN9O14
• Molecular Weight: 1038.04
• Purity: ≥95%
• Synonyms: 2-[[[2-[[(2S)-2-[[2-[[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]acetyl]amino]methoxy]ethyl N-[[(19S)-19-ethyl-6-fluoro-19-hydroxy-7-methyl-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-10-yl]methyl]carbamate
• InChI: InChI=1S/C51H56FN9O14/c1-3-51(72)35-20-39-46-33(26-61(39)48(69)34(35)27-75-49(51)70)32(31-18-29(2)36(52)21-37(31)59-46)22-56-50(71)74-17-16-73-28-57-42(64)24-55-47(68)38(19-30-10-6-4-7-11-30)58-43(65)25-54-41(63)23-53-40(62)12-8-5-9-15-60-44(66)13-14-45(60)67/h4,6-7,10-11,13-14,18,20-21,38,72H,3,5,8-9,12,15-17,19,22-28H2,1-2H3,(H,53,62)(H,54,63)(H,55,68)(H,56,71)(H,57,64)(H,58,65)/t38-,51-/m0/s1
• InChIKey: LMQIUJUWNKZJEB-HGWGJBHZSA-N
• SMILES: CCC1(C2=C(COC1=O)C(=O)N3CC4=C(C5=C(C=C(C(=C5)C)F)N=C4C3=C2)CNC(=O)OCCOCNC(=O)CNC(=O)C(CC6=CC=CC=C6)NC(=O)CNC(=O)CNC(=O)CCCCCN7C(=O)C=CC7=O)O

MC-GGFG-AM-(10Me-11F-Camptothecin) is a linker-payload conjugate used to synthesize ZW251. ZW251 an antibody-drug conjugate (ADC) targeting human GPC3. ZW251 consists of a humanized IgG1 antibody conjugated to a novel camptothecin-based topoisomerase 1 inhibitor, ZD06519, via a linker. The linker is the maleimide anchor and a glycyl glycyl phenylalanyl glycine (GGFG)-aminomethyl (AM) cleavable linker. ZW251 has high affinity with human and cynomolgus monkey GPC3. ZW251 displays rapid internalization in GPC3-expressing HCC cell lines, and bystander-mediated killing of GPC3 negative cancer cells[1].

Reference

[1]. Madera L, et al. ZW251, a novel glypican-3-targeting antibody drug conjugate bearing a topoisomerase 1 inhibitor payload[J]. Cancer Research, 2023, 83(7_Supplement): 2658-2658.