APR-1602

APR-1602 is a potent and selective small molecule inhibitor of **Ubiquitin Specific Peptidase 1 (USP1)**, a deubiquitinating enzyme that plays a critical role in the DNA Damage Response (DDR). USP1 is responsible for the deubiquitination of key proteins involved in DNA repair pathways, including PCNA (proliferating cell nuclear antigen) and FANCD2, which are essential for translesion synthesis and the Fanconi Anemia pathway, respectively. By inhibiting USP1, APR-1602 prevents the recycling of these proteins, leading to the accumulation of ubiquitinated substrates, increased replication stress, and DNA double-strand breaks. This mechanism is designed to exploit **synthetic lethality** in cancer cells that are already deficient in homologous recombination (HR), such as those with BRCA1 or BRCA2 mutations. Developed by **Aprea Therapeutics** following its acquisition of **Atrin Pharmaceuticals**, APR-1602 is being investigated as a targeted therapy for solid tumors, particularly those with homologous recombination deficiency (HRD).