KRAS Mutant

Class

small molecule

Notes

original target text: KRAS Mutant Inhibitor

KRAS is a small enzyme called a GTPase that acts as a molecular switch in cells, cycling between an active, signal-transmitting state (bound to GTP) and an inactive state (bound to GDP). It sits at the top of the RAS-RAF-MEK-ERK pathway, which relays growth signals from receptors on the cell surface to the nucleus, driving cell division. In many cancers, point mutations in KRAS (commonly at codon 12) impair its ability to switch off, leaving it locked in the active state and producing continuous, unregulated growth signaling. Because KRAS mutations are among the most frequent oncogenic drivers across solid tumors, including cancers of the lung, colon, and pancreas, developing agents that selectively inhibit the mutant protein while sparing normal KRAS has been a long-standing goal. Mutant-selective small molecules aim to shut down this aberrant signaling directly at its source, distinguishing tumor cells from healthy tissue that relies on normal RAS function. This approach broadly matters wherever a driving mutation of this kind confers a tumor's proliferative and survival advantage, making direct inhibition of the mutant protein a rational strategy rather than only targeting downstream pathway components.