Abstract
KRAS is the most commonly mutated isoform in RAS-driven cancers. In the early stage, KRAS was deemed as an "undruggable" cancer target due to the lack of suitable binding pockets. With the development of KRAS inhibitors in recent years, strategies that directly suppress oncogenic KRAS have achieved significant breakthroughs. In this review, we summarize recent advances in direct small-molecule KRAS inhibitors used for cancer therapy, highlighting their medicinal chemistry optimization processes. Moreover, new PROTACs targeting the KRAS mutation are also presented. Additionally, we put forward the challenges and prospects for the development of future KRAS inhibitors.