Characterization of the binding of MRTX1133 as an avenue for the discovery of potential KRAS^G12D inhibitors for cancer therapy.

ABSTRACT: The Kirsten rat sarcoma (KRAS) oncoprotein has been on drug hunters list for decades now. Initially considered undruggable, recent advances have successfully broken the jinx through covalent inhibition that exploits the mutated cys12 in the switch II binding pocket (KRAS^G12C). Though this approach has achieved some level of success, patients with mutations other than cys12 are still uncatered for. KRAS^G12D is the most frequent KRAS mutated oncoprotein. It is only until recently, MRTX1133 has been discovered as a potential inhibitor of KRAS^G12D. This study seeks to unravel the structural binding mechanism of MRTX1133 as well as identify potential drug leads of KRAS^G12D based on structural binding characteristics of MRTX1133. It was revealed that M

SUBMITTER: Issahaku AR 

PROVIDER: S-EPMC9588042 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature