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Target intelligence / Profile preview
RAS family of GTPases (HRAS, KRAS, NRAS) (RAS)
- Target
- RAS
- Molecular classification
- Small GTPase, G protein
01
Overview
The RAS family of GTPases (HRAS, KRAS, and NRAS) are small GTPases that function as molecular switches in cell signaling pathways, regulating cell proliferation, differentiation, and survival. Mutations in RAS proteins are common oncogenic drivers in human cancers. They cycle between an active GTP-bound state and an inactive GDP-bound state, regulated by GEFs and GAPs. Isoforms differ in posttranslational modifications and membrane localization, potentially leading to unique signal outputs. While HRAS and NRAS knockouts are viable, KRAS knockout is embryonically lethal.
- Other names
- HRASKRASNRASGTPase HRasGTPase KRasGTPase NRasKRAS4AKRAS4B
02
Mechanism of action
Direct inhibition of KRAS^G12C^
03
Biological functions
Signal transductionCell proliferationCell differentiationCell survivalCytoskeletal organization
04
Disease associations
CancerSquamous cell carcinomaHematologic malignanciesLeukemia
05
Safety considerations
Historically considered "undruggable" due to high nucleotide affinity and lack of deep binding pocketsTissue-specific prevalence of mutations requires careful consideration of therapeutic strategiesPotential for resistance mechanisms to emergeOn-target and off-target toxicities
06
Interacting drugs
Sotorasib (AMG510)
07
Biomarkers
KRAS^G12C^ mutationKRAS^G12D^ mutation
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