Debio-0513

Debio-0513 is a potent, highly selective, and reversible small molecule inhibitor of Ubiquitin-Specific Protease 1 (USP1), currently under development by Debiopharm. USP1 is a key deubiquitinating enzyme involved in the DNA damage response (DDR), specifically regulating the Fanconi Anemia (FA) pathway and translesion synthesis (TLS) by deubiquitinating FANCD2 and PCNA. By inhibiting USP1, Debio-0513 promotes the accumulation of ubiquitinated substrates, leading to genomic instability and cell death, particularly in cancers with homologous recombination deficiencies (HRD). It is being evaluated in Phase 1/2 clinical trials for advanced solid tumors, both as a monotherapy and in combination with PARP inhibitors or chemotherapy, aiming to overcome resistance mechanisms in DDR-deficient cancers.