KRAS genes belong to the most frequently mutated family of oncogenes in cancer. 
The G12C mutation, found in a third of lung, half of colorectal and pancreatic 
cancer cases, is believed to be responsible for a substantial number of cancer 
deaths. For 30 years, KRAS has been the subject of extensive drug-targeting 
efforts aimed at targeting KRAS protein itself, but also its post-translational 
modifications, membrane localization, protein-protein interactions and 
downstream signalling pathways. So far, most KRAS targeting strategies have 
failed, and there are no KRAS-specific drugs available. However, clinical 
candidates targeting the KRAS G12C protein have recently been developed. MRTX849 
and recently approved Sotorasib are covalent binders targeting the mutated 
cysteine 12, occupying Switch II pocket.Herein, we describe two fragment 
screening drug discovery campaigns that led to the identification of binding 
pockets on the KRAS G12C surface that have not previously been described. One 
screen focused on non-covalent binders to KRAS G12C, the other on covalent 
binders.