ZM-2311

ZM-2311 is a novel, highly potent, small-molecule inhibitor of DNA polymerase theta (Polθ, encoded by POLQ) with an IC50 of 24 nM. Developed by Simcere Zaiming, ZM-2311 targets the microhomology-mediated end joining (MMEJ) pathway, which is up-regulated as a backup double-strand break repair mechanism in homologous recombination (HR)-deficient cells. By inhibiting Polθ, ZM-2311 induces synthetic lethality in HR-deficient tumors, such as those with BRCA1/2 mutations. Preclinical studies demonstrate that ZM-2311 has robust monotherapy anti-tumor activity and exhibits strong synergistic effects when combined with PARP inhibitors, ATR inhibitors, chemotherapy, or radiotherapy, while maintaining a low risk of hematotoxicity.