SPR03

SPR03 is a small molecule inhibitor of Ubiquitin-specific protease 1 (USP1) currently in preclinical development by Shanghai Sipurui Pharmaceutical Technology for the treatment of solid tumors. USP1 is a deubiquitinating enzyme that plays a pivotal role in DNA damage response (DDR) pathways, specifically by regulating the monoubiquitination status of FANCD2 and PCNA. Inhibition of USP1 by SPR03 leads to the accumulation of ubiquitinated substrates, which disrupts DNA repair mechanisms and induces synthetic lethality in cancer cells, particularly those with homologous recombination deficiency (HRD). This approach is being explored as a potential strategy to overcome resistance to PARP inhibitors or to provide a synergistic effect when used in combination therapy.