Evofosfamide

Evofosfamide is a hypoxia-activated prodrug of the cytotoxin bromo-isophosphoramide mustard (Br-IPM). Evofosfamide is stable under normoxic conditions but is activated by cellular reductases in hypoxic conditions (IC₅₀ values are 5.1 μM and 0.019 μM, in NSCLC cells under normoxic and hypoxic conditions, respectively). Br-IPM acts as a DNA alkylating agent, inducing intrastrand and interstrand crosslinks. Evofosfamide inhibits NEPC PDX tumor growth by 84.5% in adeno-CRPC and NEPC patient-derived xenograft models. When combined with gemcitabine (Cat. No. 3259), Evofosfamide inhibits primary tumor growth by 96% and significantly extends the survival time in the MIA PaCa-2 human pancreatic cancer orthotopic xenograft model.