Review maps crystallographic binding features of class Ib c-MET inhibitors like capmatinib
- This review examines class Ib c-MET kinase inhibitors, including capmatinib, savolitinib, glumetinib and vebreltinib, using X-ray structures reported from 2008 to 2026.
- It dissects how the nitrogen-containing bicyclic core and the two peripheral aromatic groups contribute to binding in the c-MET active site.
- Binding appears dominated by a conserved network of pi-based contacts, with Met1211 and Tyr1230 as key anchor points, supported by a conserved hydrogen bond involving Asp1222.
💡 Points
If Met1211/Tyr1230 pi-stacking plus the Asp1222 H-bond is truly conserved across all four drugs, then the bicyclic core is a replaceable hinge-adjacent scaffold, and potency lives in the two aromatic arms. That's a usable design rule for scaffold hopping. What I'd want next: whether selectivity over other kinases comes from these same contacts or from the periphery.