General Information of Drug Therapeutic Target (DTT) (ID: TTQ9K3Y)

DTT Name Serine/threonine-protein kinase Raf (RAF)
Synonyms Proto-oncogene Raf
Gene Name ARAF
DTT Type
Clinical trial target
[1]
UniProt ID
ARAF_HUMAN ; BRAF_HUMAN ; RAF1_HUMAN
TTD ID
T51883
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MEPPRGPPANGAEPSRAVGTVKVYLPNKQRTVVTVRDGMSVYDSLDKALKVRGLNQDCCV
VYRLIKGRKTVTAWDTAIAPLDGEELIVEVLEDVPLTMHNFVRKTFFSLAFCDFCLKFLF
HGFRCQTCGYKFHQHCSSKVPTVCVDMSTNRQQFYHSVQDLSGGSRQHEAPSNRPLNELL
TPQGPSPRTQHCDPEHFPFPAPANAPLQRIRSTSTPNVHMVSTTAPMDSNLIQLTGQSFS
TDAAGSRGGSDGTPRGSPSPASVSSGRKSPHSKSPAEQRERKSLADDKKKVKNLGYRDSG
YYWEVPPSEVQLLKRIGTGSFGTVFRGRWHGDVAVKVLKVSQPTAEQAQAFKNEMQVLRK
TRHVNILLFMGFMTRPGFAIITQWCEGSSLYHHLHVADTRFDMVQLIDVARQTAQGMDYL
HAKNIIHRDLKSNNIFLHEGLTVKIGDFGLATVKTRWSGAQPLEQPSGSVLWMAAEVIRM
QDPNPYSFQSDVYAYGVVLYELMTGSLPYSHIGCRDQIIFMVGRGYLSPDLSKISSNCPK
AMRRLLSDCLKFQREERPLFPQILATIELLQRSLPKIERSASEPSLHRTQADELPACLLS
AARLVP
Function
Participate in the RAS-RAF-MEK-ERK signal transduction cascade, also referred to as the mitogen-activated protein kinase (MAPK) cascade. Activation of RAF kinases requires interaction with RAS-GTPases.
KEGG Pathway
EGFR tyrosine kinase inhibitor resistance (hsa01521 )
Endocrine resistance (hsa01522 )
MAPK signaling pathway (hsa04010 )
ErbB signaling pathway (hsa04012 )
FoxO signaling pathway (hsa04068 )
Vascular smooth muscle contraction (hsa04270 )
Natural killer cell mediated cytotoxicity (hsa04650 )
Long-term potentiation (hsa04720 )
Serotonergic synapse (hsa04726 )
Long-term depression (hsa04730 )
Regulation of actin cytoskeleton (hsa04810 )
Insulin signaling pathway (hsa04910 )
Progesterone-mediated oocyte maturation (hsa04914 )
Parathyroid hormone synthesis, secretion and action (hsa04928 )
Alzheimer disease (hsa05010 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Alcoholism (hsa05034 )
Hepatitis C (hsa05160 )
Hepatitis B (hsa05161 )
Pathways in cancer (hsa05200 )
Proteoglycans in cancer (hsa05205 )
Chemical carcinogenesis - reactive oxygen species (hsa05208 )
Colorectal cancer (hsa05210 )
Renal cell carcinoma (hsa05211 )
Pancreatic cancer (hsa05212 )
Endometrial cancer (hsa05213 )
Glioma (hsa05214 )
Prostate cancer (hsa05215 )
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 )
Reactome Pathway
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 )
Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955 )
Signaling downstream of RAS mutants (R-HSA-9649948 )
Signaling by RAF1 mutants (R-HSA-9656223 )
SHOC2 M1731 mutant abolishes MRAS complex function (R-HSA-9726840 )
Gain-of-function MRAS complexes activate RAF signaling (R-HSA-9726842 )
RAF activation (R-HSA-5673000 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
3 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
MLN2480 DMBR8NF Solid tumour/cancer 2A00-2F9Z Phase 2 [1]
RO-5126766 DM3U9BY Non-small-cell lung cancer 2C25 Phase 2 [2]
LY3009120 DM6PFCN Solid tumour/cancer 2A00-2F9Z Phase 1 [3]
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References

1 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2 The dual RAF/MEK inhibitor CH5126766/RO5126766 may be a potential therapy for RAS-mutated tumor cells.PLoS One.2014 Nov 25;9(11):e113217.
3 Company report (eli lily)