PR-104 (sodium)

PR-104 (sodium) is a selective hypoxia-activated DNA cross-linking agent and can be used for the research of multiple tumor xenograft models. PR-104 (sodium), as a nitrogen mustard pre-prodrug, is converted efficiently to the more lipophilic dinitrobenzamide mustards alcohol PR-104A^[1]. In Vitro: PR-104 (sodium) (80 μM; 1 hour; SiHa cells) shows greater suppression of radiation-induced DNA single-strand breaks under hypoxic than aerobic conditions. PR-104 (sodium) (100 μM; 1 hour; SiHa cells) results in phosphorylation of Ser139 of histone H2AX (gH2AX). PR-104 (sodium) (0.266 mmol/kg; 18 h; SiHa cells) shows activity against hypoxic cells after irradiation. PR-104 (sodium) varies in potency between cell lines, with the lowest IC₅₀ (0.51 μmol/L) in H460 cells and highest (7.3 μmol/L) in PC3 prostate cells^[1]. In Vivo: PR-104 (sodium) (0.56 mmol/kg; i.v. or i.p.; 0~2 hours) makes the plasma area under the curve. PR-104 (sodium) (0.23 mmol/kg; i.p.; 100 days) shows antitumor activity^[1].