ICT2700

ICT2700 is a preclinical-stage, tumor-selective duocarmycin prodrug (specifically a chloromethylpyrroloindoline bioprecursor) designed for bioactivation by cytochrome P450 enzymes, primarily CYP1A1. It was developed by the Institute of Cancer Therapeutics at the University of Bradford and its spinout company, Incanthera. ICT2700 lacks the phenolic hydroxyl group of active duocarmycins, rendering it relatively non-toxic. Upon entering tumor cells expressing CYP1A1, it undergoes regioselective aryl oxidation (hydroxylation) to generate an active seco-duocarmycin metabolite (ICT2740), which rapidly undergoes spirocyclization to form an ultrapotent DNA minor groove alkylating agent. This active species binds to DNA and causes double-strand breaks, leading to cell death. ICT2700 has been investigated for the treatment of CYP1A1-expressing malignancies, including bladder cancer, head and neck cancer, and breast cancer (particularly in combination with PARP inhibitors like olaparib).

Other names

(1-chloromethyl-1,6-dihydro-2H-3,6-diaza-as-indacen-3-yl)-(6-methoxy-1H-indol-2-yl)-methanonede OH CPI MIde-OH-CPI-MIdeOHCPIMI