WNC0901

WNC0901 is a potent and selective small molecule inhibitor of DNA-dependent protein kinase (DNA-PK), a key enzyme in the non-homologous end joining (NHEJ) pathway of DNA double-strand break repair. By inhibiting DNA-PK, WNC0901 acts as a radiosensitizer, enhancing the efficacy of radiation therapy in radioresistant solid tumors such as lung carcinoma, osteosarcoma, and colorectal cancer. In preclinical studies, it has demonstrated significant inhibition of radiation-induced DNA-PK autophosphorylation and robust delay in tumor regrowth when combined with radiation, showing superior efficacy compared to other DNA-PK inhibitors like peposertib in certain models. It is metabolized into a demethylated form, WNC0901-M, which also retains potent DNA-PK inhibitory activity.