SS008871

SS008871 is a novel, potent small molecule inhibitor of DNA polymerase theta (Polθ), an enzyme critical for the microhomology-mediated end joining (MMEJ) DNA repair pathway. Developed by Simcere (Simcere Zaiming), the compound targets tumors with homologous recombination (HR) deficiency, such as those harboring BRCA1 or BRCA2 mutations, through a synthetic lethality approach. SS008871 demonstrates an IC50 of 22 nM and shows high selectivity (>125-fold) for HR-deficient cells over wild-type cells. In preclinical models, it has shown significant anti-tumor activity both as a monotherapy and in combination with PARP inhibitors like olaparib, where it can induce tumor regression. It is currently being investigated for the treatment of HR-deficient solid tumors, including gynecologic cancers.