N10-(p-nitrobenzylcarbamate) PBD prodrug

N10-(p-nitrobenzylcarbamate) PBD prodrug is a bioreductive pyrrolobenzodiazepine (PBD) derivative designed for use in Gene-Directed Enzyme Prodrug Therapy (GDEPT). Developed by Spirogen Ltd in collaboration with the University of London, this prodrug features a bulky p-nitrobenzylcarbamate protecting group at the N10-position of the PBD scaffold. This modification sterically hinders the molecule's ability to form a covalent aminal bond with the C2-NH2 of guanine bases in the DNA minor groove, thereby significantly reducing its systemic toxicity. In the presence of the nitroreductase (NTR) enzyme—often delivered via a tumor-specific promoter like telomerase in GDEPT strategies—the nitro group is reduced to an amine. The resulting p-aminobenzylcarbamate undergoes spontaneous self-immolation, releasing the potent, DNA-alkylating parent PBD. Preclinical studies have demonstrated significant sensitization in NTR-transfected human cancer cell lines (ovarian, lung, cervical, and bladder) and anti-tumor activity in mouse xenograft models.

Other names

N10-protected pyrrolobenzodiazepine prodrugN-10-protected pyrrolobenzodiazepine prodrugN 10-protected pyrrolobenzodiazepine prodrugbioreductive PBD prodrug