Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT3LH46)

DTT Name KRAS G12C mutant (KRAS G12C)
Gene Name KRAS
DTT Type
Clinical trial target
 [1]
UniProt ID
RASK_HUMAN
TTD ID
T59480
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAG
QEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDL
PSRTVDTKQAQDLARSYGIPFIETSAKTRQRVEDAFYTLVREIRQYRLKKISKEEKTPGC
VKIKKCIIM
KEGG Pathway
EGFR tyrosine kinase inhibitor resistance (hsa01521 )
Endocrine resistance (hsa01522 )
MAPK signaling pathway (hsa04010 )
ErbB signaling pathway (hsa04012 )
Ras signaling pathway (hsa04014 )
Rap1 signaling pathway (hsa04015 )
Chemokine signaling pathway (hsa04062 )
FoxO signaling pathway (hsa04068 )
Sphingolipid signaling pathway (hsa04071 )
Phospholipase D signaling pathway (hsa04072 )
Mitophagy - animal (hsa04137 )
Autophagy - animal (hsa04140 )
mTOR signaling pathway (hsa04150 )
PI3K-Akt signaling pathway (hsa04151 )
Apoptosis (hsa04210 )
Longevity regulating pathway (hsa04211 )
Longevity regulating pathway - multiple species (hsa04213 )
Cellular senescence (hsa04218 )
Axon guidance (hsa04360 )
VEGF signaling pathway (hsa04370 )
Apelin signaling pathway (hsa04371 )
Gap junction (hsa04540 )
Signaling pathways regulating pluripotency of stem cells (hsa04550 )
C-type lectin receptor signaling pathway (hsa04625 )
Natural killer cell mediated cytotoxicity (hsa04650 )
T cell receptor signaling pathway (hsa04660 )
B cell receptor signaling pathway (hsa04662 )
Fc epsilon RI signaling pathway (hsa04664 )
Thermogenesis (hsa04714 )
Long-term potentiation (hsa04720 )
Neurotrophin signaling pathway (hsa04722 )
Cholinergic synapse (hsa04725 )
Serotonergic synapse (hsa04726 )
Long-term depression (hsa04730 )
Regulation of actin cytoskeleton (hsa04810 )
Insulin signaling pathway (hsa04910 )
GnRH signaling pathway (hsa04912 )
Progesterone-mediated oocyte maturation (hsa04914 )
Estrogen signaling pathway (hsa04915 )
Melanogenesis (hsa04916 )
Prolactin signaling pathway (hsa04917 )
Thyroid hormone signaling pathway (hsa04919 )
Oxytocin signaling pathway (hsa04921 )
Relaxin signaling pathway (hsa04926 )
GnRH secretion (hsa04929 )
AGE-RAGE signaling pathway in diabetic complications (hsa04933 )
Growth hormone synthesis, secretion and action (hsa04935 )
Aldosterone-regulated sodium reabsorption (hsa04960 )
Alzheimer disease (hsa05010 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Alcoholism (hsa05034 )
Hepatitis C (hsa05160 )
Hepatitis B (hsa05161 )
Human cytomegalovirus infection (hsa05163 )
Human papillomavirus infection (hsa05165 )
Human T-cell leukemia virus 1 infection (hsa05166 )
Kaposi sarcoma-associated herpesvirus infection (hsa05167 )
Human immunodeficiency virus 1 infection (hsa05170 )
Pathways in cancer (hsa05200 )
Viral carcinogenesis (hsa05203 )
Proteoglycans in cancer (hsa05205 )
MicroRNAs in cancer (hsa05206 )
Chemical carcinogenesis - receptor activation (hsa05207 )
Chemical carcinogenesis - reactive oxygen species (hsa05208 )
Colorectal cancer (hsa05210 )
Renal cell carcinoma (hsa05211 )
Pancreatic cancer (hsa05212 )
Endometrial cancer (hsa05213 )
Glioma (hsa05214 )
Prostate cancer (hsa05215 )
Thyroid cancer (hsa05216 )
Melanoma (hsa05218 )
Bladder cancer (hsa05219 )
Chronic myeloid leukemia (hsa05220 )
Acute myeloid leukemia (hsa05221 )
Non-small cell lung cancer (hsa05223 )
Breast cancer (hsa05224 )
Hepatocellular carcinoma (hsa05225 )
Gastric cancer (hsa05226 )
Central carbon metabolism in cancer (hsa05230 )
Choline metabolism in cancer (hsa05231 )
PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235 )
Lipid and atherosclerosis (hsa05417 )
Reactome Pathway
Activation of RAS in B cells (R-HSA-1169092 )
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants (R-HSA-1236382 )
SHC1 events in ERBB2 signaling (R-HSA-1250196 )
SHC1 events in ERBB4 signaling (R-HSA-1250347 )
Signaling by SCF-KIT (R-HSA-1433557 )
Signalling to RAS (R-HSA-167044 )
p38MAPK events (R-HSA-171007 )
GRB2 events in EGFR signaling (R-HSA-179812 )
SHC1 events in EGFR signaling (R-HSA-180336 )
Downstream signal transduction (R-HSA-186763 )
GRB2 events in ERBB2 signaling (R-HSA-1963640 )
Tie2 Signaling (R-HSA-210993 )
EGFR Transactivation by Gastrin (R-HSA-2179392 )
DAP12 signaling (R-HSA-2424491 )
SHC-related events triggered by IGF1R (R-HSA-2428933 )
FCERI mediated MAPK activation (R-HSA-2871796 )
NCAM signaling for neurite out-growth (R-HSA-375165 )
Ca2+ pathway (R-HSA-4086398 )
Ras activation upon Ca2+ influx through NMDA receptor (R-HSA-442982 )
VEGFR2 mediated cell proliferation (R-HSA-5218921 )
CD209 (DC-SIGN) signaling (R-HSA-5621575 )
Constitutive Signaling by EGFRvIII (R-HSA-5637810 )
SHC-mediated cascade (R-HSA-5654688 )
FRS-mediated FGFR1 signaling (R-HSA-5654693 )
SHC-mediated cascade (R-HSA-5654699 )
FRS-mediated FGFR2 signaling (R-HSA-5654700 )
SHC-mediated cascade (R-HSA-5654704 )
FRS-mediated FGFR3 signaling (R-HSA-5654706 )
FRS-mediated FGFR4 signaling (R-HSA-5654712 )
SHC-mediated cascade (R-HSA-5654719 )
Signaling by FGFR2 in disease (R-HSA-5655253 )
Signaling by FGFR4 in disease (R-HSA-5655291 )
Signaling by FGFR1 in disease (R-HSA-5655302 )
Signaling by FGFR3 in disease (R-HSA-5655332 )
Regulation of RAS by GAPs (R-HSA-5658442 )
RAF activation (R-HSA-5673000 )
RAF/MAP kinase cascade (R-HSA-5673001 )
MAP2K and MAPK activation (R-HSA-5674135 )
Negative regulation of MAPK pathway (R-HSA-5675221 )
Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946 )
Signaling by high-kinase activity BRAF mutants (R-HSA-6802948 )
Signaling by BRAF and RAF1 fusions (R-HSA-6802952 )
RAS signaling downstream of NF1 loss-of-function variants (R-HSA-6802953 )
Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955 )
Insulin receptor signalling cascade (R-HSA-74751 )
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases (R-HSA-8849471 )
MET activates RAS signaling (R-HSA-8851805 )
RUNX3 regulates p14-ARF (R-HSA-8951936 )
Activated NTRK2 signals through RAS (R-HSA-9026519 )
Erythropoietin activates RAS (R-HSA-9027284 )
Activated NTRK2 signals through FRS2 and FRS3 (R-HSA-9028731 )
Activated NTRK3 signals through RAS (R-HSA-9034864 )
FLT3 Signaling (R-HSA-9607240 )
Constitutive Signaling by Overexpressed ERBB2 (R-HSA-9634285 )
Estrogen-stimulated signaling through PRKCZ (R-HSA-9634635 )
RAS processing (R-HSA-9648002 )
Signaling downstream of RAS mutants (R-HSA-9649948 )
Signaling by RAF1 mutants (R-HSA-9656223 )
Signaling by ERBB2 KD Mutants (R-HSA-9664565 )
Signaling by ERBB2 ECD mutants (R-HSA-9665348 )
Signaling by ERBB2 TMD/JMD mutants (R-HSA-9665686 )
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants (R-HSA-9670439 )
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants (R-HSA-9673767 )
Signaling by PDGFRA extracellular domain mutants (R-HSA-9673770 )
Signaling by CSF3 (G-CSF) (R-HSA-9674555 )
Signaling by FLT3 fusion proteins (R-HSA-9703465 )
Signaling by FLT3 ITD and TKD mutants (R-HSA-9703648 )
Signaling by RAS GAP mutants (R-HSA-9753510 )
Signaling by RAS GTPase mutants (R-HSA-9753512 )
SOS-mediated signalling (R-HSA-112412 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
2 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Adagrasib DMDV4EP Non-small-cell lung cancer 2C25 Approved [2]
Sotorasib DMLSV74 Non-small-cell lung cancer 2C25 Approved [1]
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4 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
JDQ443 DMHI7CQ Non-small-cell lung cancer 2C25 Phase 3 [3]
LY3499446 DMA1CSR Solid tumour/cancer 2A00-2F9Z Phase 1/2 [4]
JNJ-74699157 DMY7CW1 Solid tumour/cancer 2A00-2F9Z Phase 1 [4]
RG6330 DMSX5NJ Solid tumour/cancer 2A00-2F9Z Phase 1 [5]
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References

1 Clinical pipeline report, company report or official report of Amgen.
2 Clinical pipeline report, company report or official report of Mirati Therapeutics.
3 Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, and Selective Covalent Oral Inhibitor of KRASG12C. Cancer Discov. 2022 Jun 2;12(6):1500-1517.
4 KRAS: From undruggable to a druggable Cancer Target. Cancer Treat Rev. 2020 Sep;89:102070.
5 Clinical pipeline report, company report or official report of Roche.