bromo-isophosphoramide mustard

Bromo-isophosphoramide mustard (BR-IPM) is a bifunctional alkylating agent of the nitrogen mustard class, structurally related to isophosphoramide mustard but with increased cytotoxicity due to the substitution of bromine for chlorine atoms. It is primarily known as the cytotoxic "warhead" released from the hypoxia-activated prodrug evofosfamide (TH-302). Under hypoxic conditions, evofosfamide undergoes bioreductive activation, resulting in the release of BR-IPM, which then forms highly reactive aziridinium ion intermediates. These intermediates alkylate DNA at the N7 position of guanine, leading to both intrastrand and interstrand DNA crosslinks. The extensive DNA damage induced by BR-IPM activates cellular DNA damage response pathways, cell cycle arrest, and ultimately triggers apoptosis if the damage is irreparable. BR-IPM itself is not administered directly as a stand-alone therapeutic agent in clinical use; its relevance is as the active metabolite responsible for the antitumor activity of its prodrug, evofosfamide, especially targeting hypoxic regions of tumors, where conventional treatments are less effective[1][3][5][7].

Other names

bromo-isophosphoramide mustard