JRF101

JRF101 is a potent and selective small molecule inhibitor of ubiquitin-specific protease 1 (USP1), currently being developed by Shenzhen Jinruijiye Biotechnology for the treatment of advanced solid tumors and brain tumors. USP1 is a critical deubiquitinating enzyme that regulates key DNA damage response (DDR) pathways, including the Fanconi Anemia (FA) pathway and translesion synthesis (TLS), by deubiquitinating substrates such as FANCD2 and PCNA. By inhibiting USP1, JRF101 promotes the accumulation of ubiquitinated substrates, which disrupts efficient DNA repair and replication, leading to synthetic lethality in cancer cells with existing DDR deficiencies, such as those with BRCA1/2 mutations. JRF101 is currently in Phase 1/2 clinical development, where it is being evaluated as a monotherapy and in combination with other agents, including PD-1 inhibitors.