Odafosfamide ((S)-OBI-3424) is a highly selective prodrug bi-alkylating agent activated by aldo-keto reductase 1C3 (AKR1C3). It exhibits potent cytotoxicity in cell lines with high AKR1C3 expression. Odafosfamide demonstrates antitumor activity in various tumors with elevated AKR1C3 expression, such as liver cancer, non-small cell lung cancer, and leukemia. It is applicable for cancer research.

Odafosfamide demonstrates cytotoxic effects on liver cancer cells (SNU-475, SNU-449, C3A) with high AKR1C3 protein and RNA expression levels, exhibiting IC50 values of 15 nM, 45 nM, and 5 nM, respectively, as well as on non-small cell lung cancer cells (NSCLC) such as NCI-H1944, NCI-H2228, NCI-H1755, NCI-H1563, NCI-H2110, and NCI-H1792, with IC50 values of 2.3 nM, 0.21 nM, 8.2 nM, 2.5 nM, 1.1 nM, and 4.5 nM. Additionally, odafosfamide shows potential anti-leukemic activity against 19 leukemia cell lines representing B-ALL, T-ALL, and ETP-ALL, with IC50 values of 60.3 nmol/L, 9.7 nmol/L, and 31.5 nmol/L, respectively.

Odafosfamide, administered via intravenous injection at doses ranging from 1.25 to 5 mg/kg weekly for 2 weeks, effectively inhibits tumor growth in the HepG2 orthotopic xenograft model. Similarly, doses of 0.625 to 1.25 mg/kg weekly for 2 cycles, followed by a one-week break and then 2 additional cycles, suppress tumor growth in the H460 subcutaneous graft model. In doses of 2.5 mg/kg to 5 mg/kg, given intravenously once a week for 4 to 5 weeks, it suppresses tumors in (CRPC) VCaP, SNU-16, and A498 xenograft models. Odafosfamide, at 1.25 to 5 mg/kg weekly for 3 weeks, inhibits tumor growth in PA1280, GA6201, and LU2505 xenograft models. Administered via intraperitoneal injection at 2.5 mg/kg once a week for 3 weeks, it induces a marked and sustained regression in pediatric ALL PDX models.