Mefuparib (CVL218) is a potent, highly selective, competitive PARP1/2 inhibitor with IC50 of 3.2/1.9 nM, respectively. Mefuparib displays >406-fold over other major nuclear PARPs including PARP3, TNKS1, TNKS2 and PARP6. Mefuparib reduces poly(ADP-ribose) formation, enhances γH2AX levels, induces G2/M arrest and subsequent apoptosis in homologous recombination repair (HR)-deficient cells. Mefuparib shows potent in vitro and in vivo proliferation and growth inhibition against HR-deficient cancer cells and synergistic sensitization of HR-proficient xenografts to the anticancer drug temozolomide.
