DRH-417

DRH-417 is a synthetic pyrrolobenzodiazepine (PBD) monomer, part of the anthramycin group of antitumor antibiotics. It binds covalently to the N2 position of guanine bases in the minor groove of DNA, resulting in potent antiproliferative activity[1][3][5][7]. DRH-417 demonstrated strong in vitro cytotoxicity (mean IC50 = 3 nM) with differential sensitivity towards melanoma, breast, and renal cell carcinoma. In vivo, it showed marked antitumor activity against two human renal cell cancers, one breast cancer, and a murine colon tumor model. Its plasma pharmacokinetics indicated peak concentrations above those required for in vitro activity. Genomic profiling of sensitive tumors indicated activation of the insulin-like growth factor signaling pathway. The compound was selected and developed through the European Organisation for Research and Treatment of Cancer (EORTC) Drug Discovery Committee and the NCI 60 cell line screening programs but was ultimately discontinued when the related PBD dimer SJG-136 advanced further in clinical development[3].

Other names

NSC 7091119NSC7091119NSC-7091119