ONT-093 is an orally bioavailable substituted diarylimidazole inhibitor of P-glycoprotein ATPase activity (IC50 = 0.16 μM).1 It reverses drug resistance to doxorubicin , vinblastine , and paclitaxel in human lymphoma, breast, ovarian, uterine, and colorectal cancer cell lines in vitro (EC50s = 9-38 nM). It is not cytotoxic to 15 normal, non-transformed, or tumor cell lines when used at concentrations up to 100 μM and exhibits weak cytostatic activity (average IC50 = >60 μM). ONT-093 (30 mg/kg) reverses paclitaxel drug resistance in an HCT15 human colon carcinoma mouse xenograft model.
|1. Newman, M.J., Rodarte, J.C., Benbatoul, K.D., et al. Discovery and characterization of OC144-093, a novel inhibitor of P-glycoprotein-mediated multidrug resistance. Cancer Res. 60(11), 2964-2972 (2000).