nst-628

NST-628 is a novel, fully brain-permeable, non-degrading pan-RAF/MEK molecular glue developed by Nested Therapeutics. It acts by binding to RAF kinases and preventing the formation of BRAF–CRAF and BRAF–ARAF heterodimers, thereby inhibiting the RAS-MAPK pathway. This mechanism blocks downstream MEK and ERK phosphorylation, effectively shutting down MAPK signaling in tumor cells with RAS or RAF mutations. Preclinical studies have shown that NST-628 has broad antitumor activity across various KRAS-mutant cancer models and can overcome resistance mechanisms seen with other targeted therapies. The drug is being evaluated as an oral agent for advanced solid tumors harboring genetic alterations in the MAPK pathway, including glioma, melanoma, non-small cell lung cancer (NSCLC), pancreatic cancer, colorectal cancer, and others[1][2][3][4][5][6].