Figure 2.

Under normal conditions, KRAS drives the controlled activation of different proliferation and growth intracellular pathways. When activated by a receptor tyrosine kinase, KRAS releases GDP and binds GTP. When bound to GTP, KRAS will trigger the PI3 K/Akt/mTOR, MAPK, and NF-kB pathways. When mutated, KRAS will become permanently active, inducing uncontrolled cell proliferation. Drugs like sotorasib, adagrasib, and JNJ-74699157 permanently bind to the inactivated form of KRAS-G12 C, keeping KRAS from being activated by GTP. BI-1701963 inhibits the GEF protein SOS1, one of the main guanosine exchanging factors related to Ras proteins.