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Target intelligence / Profile preview
KRASG12D
- Target
- KRASG12D
- Molecular classification
- Small GTPase, Oncogene
01
Overview
KRASG12D is a mutant form of the KRAS protein, where glycine at position 12 is replaced by aspartic acid (G12D). This mutation impairs intrinsic GTPase activity, resulting in constitutive activation of KRAS and persistent downstream signaling—an oncogenic driver in several cancers, especially pancreatic cancer. Therapeutic targeting focuses on noncovalent inhibitors binding to unique pockets on the mutant protein.
- Other names
- KRAS G12DKRAS(G12D)KRAS p.Gly12AspKRAS c.35G>AG12D KRAS
02
Mechanism of action
Inhibition of GDP-GTP exchange; PROTAC-mediated degradation; binding to S-II pocket
03
Biological functions
Signal transductionCell proliferationCell differentiationRegulation of GTPase activity
04
Disease associations
CancerPancreatic cancerColorectal cancer
05
Safety considerations
Potential for off-target effectsDevelopment of resistanceLimited efficacy in some tumor types
06
Interacting drugs
MRTX1133
3 more in the full profile.
07
Biomarkers
KRASG12D mutation status in tumor tissueDownstream MAPK pathway activation
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