
Kras is a member of the RAS protein family, which are a class of small GTPases involved in cell signaling pathways. The Ras signaling pathway regulates diverse cellular processes, including cell proliferation, differentiation, and survival. Conversion of Ras from the inactive GDP-bound state to the active GTP-bound state activates the downstream effector and promotes cell growth. RAF is a key downstream effector of RAS. Since the frequently mutated Ras genes are associated with various human tumors, the Ras-RAF signaling pathway is considered an important therapeutic target for cancer treatment. However, Ras is considered undruggable since it lacks suitable binding pockets on the surface. Recently, a discovery of a small molecule inhibitor blocks Ras-RAF signaling pathway by remolding Cyclophilin A (CYPA) and forming a CYPA:drug:KRAS ternary complex. This inhibitory strategy provides a new method for developing drugs targeting Kras for treatment of cancers.