Kirsten rat sarcoma virus oncogene (KRAS) mutation accounts for approximately 
85% of RAS-driven cancers, and participates in multiple signaling pathways and 
mediates cell proliferation, differentiation and metabolism. KRAS has been 
considered as an "undruggable" target due to the lack of effective direct 
inhibitors, although high frequency of KRAS mutations have been identified in 
multiple carcinomas in the past decades. Encouragingly, the KRASG12C inhibitor 
AMG510 (sotorasib), which has been approved for treating NSCLC and CRC recently, 
makes directly targeting KRAS the most promising strategy for cancer therapy. To 
better understand the current state of KRAS inhibitors, this review summarizes 
the biological functions of KRAS, the structure-activity relationship studies of 
the small-molecule inhibitors that directly target KRAS, and highlights the 
therapeutic agents with improved selectivity, bioavailability and 
physicochemical properties. Furthermore, the combined medication that can 
enhance efficacy and overcome drug resistance of KRAS covalent inhibitors is 
also reviewed.