Details of the Drug Therapeutic Target (DTT)

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

DTT Name Serine/threonine-protein kinase B-raf (BRAF)
Synonyms V-Raf murine sarcoma viral oncogene homolog B1; RAFB1; Proto-oncogene B-Raf; P94; BRAF1; BRAF(V599E); BRAF serine/threonine kinase; B-raf protein; B-Raf
Gene Name BRAF
DTT Type
Successful target
 [1]
BioChemical Class
Kinase
UniProt ID
BRAF_HUMAN
TTD ID
T99089
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.7.11.1
Sequence
MAALSGGGGGGAEPGQALFNGDMEPEAGAGAGAAASSAADPAIPEEVWNIKQMIKLTQEH
IEALLDKFGGEHNPPSIYLEAYEEYTSKLDALQQREQQLLESLGNGTDFSVSSSASMDTV
TSSSSSSLSVLPSSLSVFQNPTDVARSNPKSPQKPIVRVFLPNKQRTVVPARCGVTVRDS
LKKALMMRGLIPECCAVYRIQDGEKKPIGWDTDISWLTGEELHVEVLENVPLTTHNFVRK
TFFTLAFCDFCRKLLFQGFRCQTCGYKFHQRCSTEVPLMCVNYDQLDLLFVSKFFEHHPI
PQEEASLAETALTSGSSPSAPASDSIGPQILTSPSPSKSIPIPQPFRPADEDHRNQFGQR
DRSSSAPNVHINTIEPVNIDDLIRDQGFRGDGGSTTGLSATPPASLPGSLTNVKALQKSP
GPQRERKSSSSSEDRNRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDV
AVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQLAIVTQWCEGSSLYHH
LHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATV
KSRWSGSHQFEQLSGSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSNIN
NRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKRDERPLFPQILASIELLARS
LPKIHRSASEPSLNRAGFQTEDFSLYACASPKTPIQAGGYGAFPVH
Function
May play a role in the postsynaptic responses of hippocampal neuron. Phosphorylates MAP2K1, and thereby contributes to the MAP kinase signal transduction pathway. Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
KEGG Pathway
MAPK signaling pathway (hsa04010 )
ErbB signaling pathway (hsa04012 )
Rap1 signaling pathway (hsa04015 )
cAMP signaling pathway (hsa04024 )
Chemokine signaling pathway (hsa04062 )
FoxO signaling pathway (hsa04068 )
mTOR signaling pathway (hsa04150 )
Vascular smooth muscle contraction (hsa04270 )
Focal adhesion (hsa04510 )
Natural killer cell mediated cytotoxicity (hsa04650 )
Long-term potentiation (hsa04720 )
Neurotrophin signaling pathway (hsa04722 )
Serotonergic synapse (hsa04726 )
Long-term depression (hsa04730 )
Regulation of actin cytoskeleton (hsa04810 )
Insulin signaling pathway (hsa04910 )
Progesterone-mediated oocyte maturation (hsa04914 )
Alcoholism (hsa05034 )
Hepatitis C (hsa05160 )
Pathways in cancer (hsa05200 )
Proteoglycans in cancer (hsa05205 )
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 )
Reactome Pathway
Frs2-mediated activation (R-HSA-170968 )
ARMS-mediated activation (R-HSA-170984 )
CREB phosphorylation through the activation of Ras (R-HSA-442742 )
RAF activation (R-HSA-5673000 )
MAP2K and MAPK activation (R-HSA-5674135 )
Negative feedback regulation of MAPK pathway (R-HSA-5674499 )
Negative regulation of MAPK pathway (R-HSA-5675221 )
Spry regulation of FGF signaling (R-HSA-1295596 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
3 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Dabrafenib DMX6OE3 Melanoma 2C30 Approved [1]
LGX818 DMNQXV8 Melanoma 2C30 Approved [2]
Vemurafenib DM62UG5 Melanoma 2C30 Approved [3]
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10 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
PLX8394 DMRTD7I Solid tumour/cancer 2A00-2F9Z Phase 2 [4]
BGB-283 DMVYTG7 Solid tumour/cancer 2A00-2F9Z Phase 1/2 [5]
CEP-32496 DMAO04B Solid tumour/cancer 2A00-2F9Z Phase 1/2 [6]
ABM-1310 DMS1HR3 Solid tumour/cancer 2A00-2F9Z Phase 1 [7]
ARQ 736 DMP9ZT1 Solid tumour/cancer 2A00-2F9Z Phase 1 [8]
ASN003 DMJCX6D Solid tumour/cancer 2A00-2F9Z Phase 1 [9]
BMS-908662 DM3K8VM Solid tumour/cancer 2A00-2F9Z Phase 1 [10]
PF-07284890 DMK7XYH Melanoma 2C30 Phase 1 [11]
PF-07799933 DMHGA0S Aggressive cancer 2A00-2F9Z Phase 1 [12]
RO-5212054 DML4C3Q Solid tumour/cancer 2A00-2F9Z Phase 1 [13]
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⏷ Show the Full List of 10 Clinical Trial Drug(s)
1 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
RG-7256 DM0LXBW Melanoma 2C30 Discontinued in Phase 1 [14]
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2 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
AR-00341677 DMK2XB7 Solid tumour/cancer 2A00-2F9Z Investigative [15]
AZ-628 DMEWQHP Solid tumour/cancer 2A00-2F9Z Investigative [16]
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Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Thyroid cancer 2C82 Thyroid 3.00E-01 0.1 0.2
Melanoma 2C82 Skin 1.19E-02 0.45 0.73
Myelodysplastic syndrome 2C82 Bone marrow 7.80E-01 0.05 0.08
Breast cancer 2C82 Breast tissue 4.81E-15 0.29 0.47
Acute myelocytic leukaemia 2C82 Bone marrow 5.37E-03 -0.23 -0.36
Head and neck cancer 2C82 Head and neck tissue 5.14E-02 -0.13 -0.27
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⏷ Show the Full List of DTT Expression Under 6 Diseases

References

1 Clinical pipeline report, company report or official report of GlaxoSmithKline (2011).
2 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 Identification of PLX4032-resistance mechanisms and implications for novel RAF inhibitors. Pigment Cell Melanoma Res. 2014 Mar;27(2):253-62.
5 BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF-Mutated Colorectal Cancers. Mol Cancer Ther. 2015 Oct;14(10):2187-97.
6 Clinical pipeline report, company report or official report of Ambit Biosciences.
7 Clinical pipeline report, company report or official report of ABM Therapeutics.
8 National Cancer Institute Drug Dictionary (drug id 688029).
9 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
10 Clinical pipeline report, company report or official report of Exelixis (2011).
11 Clinical pipeline report, company report or official report of Pfzer
12 ClinicalTrials.gov (NCT05355701) A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTI TUMOR ACTIVITY OF PF-07799933 (ARRY-440) AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS 16 YEARS AND OLDER WITH ADVANCED SOLID TUMORS WITH BRAF ALTERATIONS. U.S.National Institutes of Health.
13 National Cancer Institute Drug Dictionary (drug id 680347).
14 First-in-Man Dose-Escalation Study of the Selective BRAF Inhibitor RG7256 in Patients with BRAF V600-Mutated Advanced Solid Tumors. Target Oncol. 2016 Apr;11(2):149-56.
15 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5681).
16 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8475).