AG14361

AG14361 is a **potent and selective inhibitor of poly(ADP-ribose) polymerase 1 (PARP-1)**, a nuclear enzyme essential for DNA base excision repair. Its inhibitory constant (Ki) is less than 5 nM, and it is over 1000-fold more potent than classical benzamide PARP inhibitors[7][10][1]. By blocking PARP-1 activity, AG14361 impairs DNA repair in cancer cells, especially those already deficient in homologous recombination (such as BRCA-deficient tumors), leading to enhanced cell death when combined with DNA-damaging agents or radiation[1][2][3][6]. AG14361 has shown strong **chemosensitization and radiosensitization** properties, enhancing the antitumor effects of drugs like temozolomide, irinotecan, and topotecan, and inducing complete regression in some tumor xenograft models[2][3][6][5]. The molecule is water-soluble and was developed through structure-based drug design to improve potency, specificity, and pharmacokinetics over earlier PARP inhibitors[2][3][6][10]. Preclinical studies have demonstrated its effectiveness in overcoming chemoresistance tied to DNA repair deficits, particularly in mismatch repair-deficient and BRCA2-deficient models[1][5].

Other names

AG14361AG-14361AG 14361