GS-P-328

GS-P-328 is a brain-penetrant small molecule reactivator of the p53 Y220C mutant protein, developed by Changchun GeneScience Pharmaceutical. The Y220C mutation is a common oncogenic missense mutation that creates a hydrophobic pocket on the p53 DNA-binding domain, leading to thermal instability and protein unfolding under physiological conditions. GS-P-328 binds to this pocket with nanomolar potency, stabilizing the protein and restoring its wild-type tumor-suppressive transcriptional activity. This restoration leads to the upregulation of downstream targets such as MDM2 and p21, inducing apoptosis in cancer cells. In preclinical studies, GS-P-328 has demonstrated significant anti-tumor activity across various models, including small cell lung cancer (SCLC), gastric, ovarian, and colon cancers. Notably, its ability to cross the blood-brain barrier has been shown to inhibit cancer cell growth in intracranial models, potentially addressing a significant unmet need for tumors with CNS involvement.