WSD0628 + WNC0901

WSD0628 + WNC0901 is a combination of two small-molecule kinase inhibitors designed to enhance radiosensitization in brain tumors by concurrently blocking DNA damage response pathways. WSD0628 is a brain-penetrant ATM (ataxia-telangiectasia mutated) inhibitor that potently suppresses radiation-induced ATM signaling, including phosphorylation of KAP1 and Chk2, while demonstrating high selectivity across 216 kinases, oral bioavailability, low hERG liability, and favorable CNS penetration (unbound brain partition coefficient 0.15-0.3). WNC0901 is a novel DNA-PK (DNA-dependent protein kinase) inhibitor that inhibits phosphorylation of DNA-PKcs, complementing ATM inhibition to disrupt non-homologous end joining repair. Developed by Wayshine Biopharm, this pairing targets glioblastoma and other high-grade gliomas, showing preclinical synergy with radiation therapy in enhancing tumor cell killing while raising considerations for normal tissue toxicity.[1][2][9][13]