Is RAS a druggable target?
Small molecules that bind in the DCAI pocket prevent SOS1-mediated guanine exchange and so RAS proteins cannot adopt the GTP-bound active state, making this pocket a desirable drug target.
Why is it hard to target RAS?
Activated Ras is an extremely challenging direct drug target due to the inherent difficulties in disrupting the protein:protein interactions that underlie its activation and function. Major investments have been made to target Ras through indirect routes.
Is RAS Druggable?
ABSTRACT. RAS mutations are the most common oncogenic drivers across human cancers, but there remains a paucity of clinically-validated pharmacological inhibitors of RAS, as druggable pockets have proven difficult to identify.
Is RAS a target protein?
Ras genes are frequently mutated in human cancers, and the proteins they encode have been considered drug targets since they were first identified and characterized 30 years ago.
Why are Ras targeted therapies called undruggable?
RAS-targeted therapies: is the undruggable drugged? RAS (KRAS, NRAS and HRAS) is the most frequently mutated gene family in cancers, and, consequently, investigators have sought an effective RAS inhibitor for more than three decades. Even 10 years ago, RAS inhibitors were so elusive that RAS was termed ‘undruggable’.
Are there any new therapies for Ras driven cancer?
Now, with the success of allele-specific covalent inhibitors against the most frequently mutated version of RAS in non-small-cell lung cancer, KRASG12C, we have the opportunity to evaluate the best therapeutic strategies to treat RAS-driven cancers.
Are there any Ras targeted therapies on the market?
However, a clinically approved mutant selective KRAS therapy is now within sight as the FDA has granted an allele-specific covalent inhibitor, AMG 510, Fast Track designation 1. AMG 510 binds to KRAS-G12C, the RAS mutatant most commonly found in non-small-cell lung tumours.
Are there any targeted therapies for kras-g12c?
This successful inhibition of KRAS-G12C, has given hope that a range of mutant RAS allele-specific targeted therapies could become therapeutically tractable. In normal cells, RAS is activated at the membrane downstream of growth factor receptors, including members of the epidermal growth factor receptor (EGFR) family (Fig. 1 ).
