ETX-19477

ETX-19477 is a novel, potent, orally bioavailable small molecule inhibitor of poly(ADP-ribose) glycohydrolase (PARG), an enzyme involved in the regulation of DNA repair and cellular transcriptional activity. By inhibiting PARG, ETX-19477 causes accumulation of poly(ADP-ribose) (PAR) chains within cells, leading to hyperPARylation and targeted death of cancer cells experiencing replication stress. Preclinical studies have demonstrated strong antiproliferative effects across various tumor types—including ER+HER2− breast cancer, ovarian cancer, lung cancer, and gastric cancer—and favorable pharmacokinetics. The drug is being developed by 858 Therapeutics for the treatment of advanced solid tumors and entered Phase 1 clinical trials in May 2024[1][3][5][6].