PR-104 is a highly specific hypoxia-activated agent that cross-links DNA, enabling its application in various tumor xenograft models. Functioning as a pre-prodrug of nitrogen mustard, PR-104 undergoes efficient conversion to the dinitrobenzamide mustards alcohol form, known as PR-104A[1].

PR-104 (80 μM; 1 hour; SiHa cells) shows greater suppression of radiation-induced DNA single-strand breaks under hypoxic than aerobic conditions. PR-104 (100 μM; 1 hour; SiHa cells) results in phosphorylation of Ser139 of histone H2AX (gH2AX). PR-104 (0.266 mmol/kg; 18 h; SiHa cells) shows activity against hypoxic cells after irradiation. PR-104 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].

PR-104 (0.56 mmol/kg; i.v. or i.p.; 0~2 hours) makes the plasma area under the curve. PR-104 (0.23 mmol/kg; i.p.; 100 days) shows antitumor activity[1].