BR61501

BR61501 is an orally bioavailable, highly selective small molecule inhibitor of Ubiquitin-Specific Protease 1 (USP1), currently under development by Jiangsu Wengao Pharmaceutical for the treatment of advanced solid tumors. USP1 is a key deubiquitinating enzyme involved in the DNA damage response (DDR), specifically regulating the Fanconi Anemia pathway and translesion synthesis by deubiquitinating substrates such as FANCD2 and PCNA. By inhibiting USP1, BR61501 promotes the accumulation of ubiquitinated substrates, leading to genomic instability and cell death, particularly in tumors with existing defects in homologous recombination repair (e.g., BRCA1/2 mutations). This mechanism of synthetic lethality makes BR61501 a promising candidate for patients who have progressed on or are resistant to PARP inhibitors. It is currently being evaluated in Phase 1 clinical trials to assess its safety, pharmacokinetics, and preliminary anti-tumor activity.