QLS1403

QLS1403 is a potent, small-molecule inhibitor of poly (ADP-ribose) glycohydrolase (PARG) developed by Qilu Pharmaceutical. It is specifically designed to target homologous recombination deficient (HRD) cancers, including those that have acquired resistance to PARP inhibitors (PARPi) or antibody-drug conjugates like trastuzumab deruxtecan (T-Dxd). By inhibiting PARG, the drug prevents the hydrolysis of poly (ADP-ribose) (PAR) chains, which are essential for DNA repair complex turnover. This leads to persistent replication fork stalling, DNA degradation, and synthetic lethality in HRD-positive cells. Preclinical data presented at AACR 2026 demonstrated that QLS1403 has an IC50 of 0.35 nM, showing significantly higher potency than the clinical-stage PARG inhibitor IDE-161, and achieves tumor regression in various xenograft models.