HEC228032

HEC228032 is an orally bioavailable small molecule designed as a molecular glue pan-RAS (ON) inhibitor. Developed by HEC Pharma, it functions by binding to Cyclophilin A (CypA) to form a complex that subsequently binds to the active (ON) state of various RAS mutants, including KRAS G12C, G12D, G12V, and G13D. This interaction sterically hinders the binding of RAS to its downstream effectors, such as RAF, thereby inhibiting oncogenic signaling. In preclinical studies, HEC228032 has demonstrated potent anti-proliferative activity across multiple RAS-mutant cell lines with sub-nanomolar IC50 values and induced dose-dependent tumor regression in xenograft models of pancreatic and lung cancer. It is being developed for the treatment of malignancies driven by diverse RAS mutations, including pancreatic ductal adenocarcinoma, colorectal carcinoma, and non-small cell lung cancer.