Biochem/physiol Actions

D-I03 is a selective RAD52 inhibitor (IC50 = 5 and 8 µM, respectively, by SSA and DNA pairing (D-loop formation) assay; ﹤5% RAD51 inhibition at 80 µM) that blocks single-strand DNA (ssDNA) annealing (SSA)-, but not homology dependent recombination (HDR)-, mediated double-strand break (DSB) repair (5-30 µM using respective U2OS reporter cells) and reduces nuclear RAD52, but not RAD51, foci formation (2.5 µM) upon DNA damage by cisplatin. D-I03 selectively suppresses BRCA1-deficient over BRCA1-proficient cancer cells and exerts synergistic activity with PARP1 inhibitors against BRCA1-deficient cancer both in cultures (1 & 2.5 µM) and in mice (50 mg/kg/day i.p.) in vivo.