SDT-101

SDT-101 is an orally bioavailable, potent, and selective small molecule inhibitor of Ubiquitin-specific protease 1 (USP1), currently under development by Suzhou Jinsheng Pharmaceutical for the treatment of advanced solid tumors. USP1 is a key deubiquitinating enzyme that plays a critical role in DNA damage repair (DDR) by regulating the ubiquitination status of proteins in the Fanconi Anemia (FA) pathway and translesion synthesis (TLS), such as FANCD2 and PCNA. By inhibiting USP1, SDT-101 prevents the deubiquitination of these substrates, thereby disrupting DNA repair mechanisms and inducing genomic instability. This approach is particularly promising for treating tumors with homologous recombination deficiency (HRD), including those with BRCA mutations, where it can induce synthetic lethality or enhance the efficacy of PARP inhibitors.