TH-302

TH-302 is a hypoxia-activated prodrug and DNA alkylating agent with anticancer activity. It is selectively cytotoxic to H460 human non-small cell lung cancer (NSCLC) cells grown under hypoxic over normoxic conditions (IC50s = 0.019 and 5.1 µM, respectively). Under hypoxic conditions, TH-302 undergoes a one-electron reduction to form an active radical intermediate that is then further reduced to form a DNA-intercalating hydroxylamine. Under normoxic conditions, the radical intermediate is quenched and induces reformation of the inactive nitroazole prodrug. TH-302 reduces survival of H460 and HT-29 cells in a clonogenic assay (IC50s = 0.2 and 0.2 µM, respectively). In vivo, TH-302 (33 mg/kg per day) inhibits primary tumor growth by 41% in an MIA PaCa-2-RFP mouse orthotopic xenograft model. It inhibits tumor growth by greater than 40% in Calu-6 NSCLC, H82 small cell lung, A375 melanoma, PC-3 prostate, and BxPC-3 pancreatic cancer mouse xenograft models when administered at 50 mg/kg.Formal Name: N,N'-bis(2-bromoethyl)-phosphorodiamidic acid, (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester. CAS Number: 918633-87-1. Synonyms: Evofosfamide. Molecular Formula: C9H16Br2N5O4P. Formula Weight: 449.0. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/mL, DMSO: 30 mg/mL, Ethanol: 30 mg/mL, PBS (pH 7.2): 0.3 mg/mL. lambdamax: 314 nm. SMILES: BrCCNP(OCC1=CN=C([N+]([O-])=O)N1C)(NCCBr)=O. InChi Code: InChI=1S/C9H16Br2N5O4P/c1-15-8(6-12-9(15)16(17)18)7-20-21(19,13-4-2-10)14-5-3-11/h6H,2-5,7H2,1H3,(H2,13,14,19). InChi Key: UGJWRPJDTDGERK-UHFFFAOYSA-N.