COH34

COH34 is a **novel, potent, and cell-active small molecule inhibitor** of poly(ADP-ribose) glycohydrolase (**PARG**), the major dePARylation enzyme involved in DNA repair. It binds specifically to the catalytic domain of PARG, inhibiting its activity with high selectivity (IC50 ≈ 0.37 nM). By blocking dePARylation, COH34 causes prolonged PARylation at DNA lesions and traps DNA repair factors. This mechanism results in selective lethality in cancer cells harboring DNA repair defects, particularly those with BRCA1/2 mutations, and demonstrates strong anti-cancer activity both in vitro and in vivo. Additionally, COH34 is effective against cancer cells that are resistant to PARP inhibitors and can synergistically enhance the efficacy of DNA-damaging chemotherapy agents such as cisplatin, doxorubicin, temozolomide, and camptothecin. COH34 was first identified via computational screening from the NCI database, with its preclinical development pioneered by researchers at City of Hope and characterized by low toxicity in animal models[1][3][4][5][10][13].

Other names

1-[(E)-(4-methylphenyl)sulfanyliminomethyl]naphthalen-2-ol