Ontology highlight
ABSTRACT:
SUBMITTER: Lito P
PROVIDER: S-EPMC4955282 | biostudies-literature | 2016 Feb
REPOSITORIES: biostudies-literature
Science (New York, N.Y.) 20160114 6273
It is thought that KRAS oncoproteins are constitutively active because their guanosine triphosphatase (GTPase) activity is disabled. Consequently, drugs targeting the inactive or guanosine 5'-diphosphate-bound conformation are not expected to be effective. We describe a mechanism that enables such drugs to inhibit KRAS(G12C) signaling and cancer cell growth. Inhibition requires intact GTPase activity and occurs because drug-bound KRAS(G12C) is insusceptible to nucleotide exchange factors and thu ...[more]