QLS5308

QLS5308 is an orally bioavailable small molecule inhibitor of Ubiquitin-Specific Peptidase 1 (USP1), developed by Qilu Pharmaceutical. USP1 is a deubiquitinating enzyme that plays a critical role in the DNA damage response (DDR) pathway, specifically by regulating the Fanconi Anemia (FA) and translesion synthesis (TLS) pathways through the deubiquitination of substrates such as FANCD2 and PCNA. By inhibiting USP1, QLS5308 prevents the removal of ubiquitin from these key proteins, leading to the accumulation of DNA damage and inducing synthetic lethality in cancer cells with existing homologous recombination repair deficiencies (e.g., BRCA1/2 mutations). QLS5308 is currently being evaluated in Phase I clinical trials for the treatment of advanced solid tumors, both as a monotherapy and potentially in combination with other DNA damage repair-targeting agents.