(R)-Odafosfamide

(R)-Odafosfamide (OBI-3424) is a proagent that is selectively converted by AKR1C3 (aldo-keto reductase 1C3) to a potent DNA-alkylating agent. (R)-Odafosfamide can be used for hepatocellular carcinoma, castrate-resistant prostate cancer, and acute lymphoblastic leukemia (ALL) research^[1]. In Vitro:(R)-Odafosfamide (OBI-3424) exerts potent cytotoxicity against the H460 lung cancer cell line (IC₅₀ of 4.0 nM). (R)-Odafosfamide exhibits potent cytotoxicity, in particular against cell lines derived from T-ALL with high AKR1C3 expression, with IC₅₀ values in the low nM range^[1].
(R)-Odafosfamide also exerts potent cell killing against ALL PDXs, and the median IC₅₀ values were 60.3 nM for B-ALL, 9.7 nM for T-ALL and 31.5 nM for ETP-ALL^[1]. In Vivo:(R)-Odafosfamide (OBI-3424) (0.5-2.5 mg/kg; i.p.; once weekly; for 3 weeks) treatment induces regressions in PDXs mice and results in prolongation of mouse event-free survival^[1].