A promising anticancer drug, AMG 510, was developed by Amgen with the help of novel structural insights gained from protein structures solved at the Advanced Light Source (ALS).
Mutations in a signaling protein, KRAS, are known to drive many human cancers. One specific KRAS mutation, KRAS(G12C), accounts for approximately 13% of non-small cell lung cancers, 3% to 5% of colorectal cancers, and 1% to 2% of numerous other solid tumors. Approximately 30,000 patients are diagnosed each year in the United States with KRAS(G12C)-driven cancers.
Despite their cancer-triggering significance, KRAS proteins have for decades resisted attempts to target their activity, leading many to regard these proteins as “undruggable.” Recently, however, a team led by researchers from Amgen identified a small molecule capable of inhibiting the activity of KRAS(G12C) and driving anti-tumor immunity. Protein crystallography studies at the ALS provided crucial information about the structural interactions between the potential drug molecule and KRAS(G12C).
Image: A structural map of KRAS(G12C), showing the AMG 510 molecule in the binding pocket. The yellow region depicts where AMG 510 covalently attaches to the KRAS protein.