XZP-6924

XZP-6924 is a potent and highly selective small molecule inhibitor of ubiquitin-specific protease 1 (USP1) being developed by Shandong XuanZhu Pharmaceutical (also known as Xuanzhu Biopharmaceutical). USP1 is a deubiquitinase that plays a critical role in the DNA damage response (DDR) pathway, specifically in the deubiquitination of substrates such as PCNA and FANCD2 within the Fanconi Anemia pathway and translesion synthesis. By inhibiting USP1, XZP-6924 promotes the accumulation of mono-ubiquitinated substrates, leading to genomic instability, DNA double-strand breaks, and apoptosis in cancer cells. The drug is primarily being investigated for the treatment of advanced solid tumors, including breast, ovarian, prostate, and pancreatic cancers. Preclinical evidence suggests that XZP-6924 may act synergistically with PARP inhibitors like olaparib and has the potential to overcome resistance to PARP inhibitor therapy in homologous recombination deficient (HRD) tumors. It is currently in Phase 1 clinical development.