Target Information

Target General Infomation
Target ID
T99089
Former ID
TTDS00346
Target Name
B-Raf proto-oncogene serine/threonine-protein kinase
Gene Name
BRAF
Synonyms
B-Raf; B-raf protein; BRAF serine/threonine kinase; BRAF(V599E); P94; V-Raf murine sarcoma viral oncogene homolog B1; BRAF
Target Type
Successful
Disease Cancer [ICD9: 140-229; ICD10: C00-C96]
Late-stage solid tumors [ICD9: 140-199, 210-229; ICD10: C00-C75, C7A, C7B, D10-D36, D3A]
Metastatic melanoma; Solid tumors [ICD9: 140-199, 172, 210-229; ICD10: C00-C75, C43, C7A, C7B, D10-D36, D3A]
Melanoma [ICD9: 172; ICD10: C43]
Metastatic melanoma; Thyroid cancer [ICD9:172, 140-229, 193; ICD10: C43, C73]
Function
Involved inthe transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron.
BioChemical Class
Kinase
Target Validation
T99089
UniProt ID
P15056
EC Number
EC 2.7.11.1
Sequence
MAALSGGGGGGAEPGQALFNGDMEPEAGAGAGAAASSAADPAIPEEVWNIKQMIKLTQEH
IEALLDKFGGEHNPPSIYLEAYEEYTSKLDALQQREQQLLESLGNGTDFSVSSSASMDTV
TSSSSSSLSVLPSSLSVFQNPTDVARSNPKSPQKPIVRVFLPNKQRTVVPARCGVTVRDS
LKKALMMRGLIPECCAVYRIQDGEKKPIGWDTDISWLTGEELHVEVLENVPLTTHNFVRK
TFFTLAFCDFCRKLLFQGFRCQTCGYKFHQRCSTEVPLMCVNYDQLDLLFVSKFFEHHPI
PQEEASLAETALTSGSSPSAPASDSIGPQILTSPSPSKSIPIPQPFRPADEDHRNQFGQR
DRSSSAPNVHINTIEPVNIDDLIRDQGFRGDGGSTTGLSATPPASLPGSLTNVKALQKSP
GPQRERKSSSSSEDRNRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDV
AVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQLAIVTQWCEGSSLYHH
LHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATV
KSRWSGSHQFEQLSGSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSNIN
NRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKRDERPLFPQILASIELLARS
LPKIHRSASEPSLNRAGFQTEDFSLYACASPKTPIQAGGYGAFPVH
Structure
1UWH; 1UWJ; 2FB8; 2L05; 3C4C; 3D4Q; 3IDP; 3II5; 3NY5; 3OG7; 3PPJ; 3PPK; 3PRF; 3PRI; 3PSB; 3PSD; 3Q4C; 3Q96; 3SKC; 3TV4; 3TV6; 4DBN; 4E26; 4E4X; 4EHE; 4EHG; 4FC0; 4FK3; 4G9C; 4G9R; 4H58; 4JVG; 4KSP; 4KSQ; 4MBJ; 4MNE; 4MNF; 4PP7; 4WO5; 1UWH; 1UWJ;2FB8; 2L05; 3C4C; 3D4Q; 3IDP; 3II5; 3NY5; 3OG7; 3PPJ; 3PPK; 3PRF; 3PRI; 3PSB; 3PSD; 3Q4C; 3Q96; 3SKC; 3TV4; 3TV6; 4DBN; 4E26; 4E4X; 4EHE; 4EHG; 4FC0; 4FK3; 4G9C; 4G9R; 4H58; 4JVG; 4KSP; 4KSQ; 4MBJ; 4MNE; 4MNF; 4PP7; 4WO5
Drugs and Mode of Action
Drug(s) Vemurafenib Drug Info Approved Metastatic melanoma; Thyroid cancer [524363], [541191], [551871]
LGX818 Drug Info Phase 2 Melanoma [524517], [542830]
CEP-32496 Drug Info Phase 1/2 Cancer [524329], [542805]
GSK2118436 Drug Info Phase 1/2 Metastatic melanoma; Solid tumors [550960]
PLX8394 Drug Info Phase 1/2 Melanoma [525176]
ARQ 736 Drug Info Phase 1 Late-stage solid tumors [523220]
BGB-283 Drug Info Phase 1 Cancer [549516]
BMS-908662 Drug Info Phase 1 Cancer [542884], [550635]
RO-5212054 Drug Info Phase 1 Cancer [523074]
RG-7256 Drug Info Discontinued in Phase 1 Melanoma [548158]
Inhibitor AR-00341677 Drug Info [541025]
AZ-628 Drug Info [543161]
BGB-283 Drug Info [533295]
BMS-908662 Drug Info [550635]
CEP-32496 Drug Info [550245]
GSK2118436 Drug Info [550960]
PLX8394 Drug Info [532568]
RG-7256 Drug Info [533309]
RO-5212054 Drug Info [550461]
Modulator ARQ 736 Drug Info [550466]
LGX818 Drug Info [1572591]
Vemurafenib Drug Info [551871]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
DRM DRM Info
Pathways
KEGG Pathway MAPK signaling pathway
ErbB signaling pathway
Rap1 signaling pathway
cAMP signaling pathway
Chemokine signaling pathway
FoxO signaling pathway
mTOR signaling pathway
Vascular smooth muscle contraction
Focal adhesion
Natural killer cell mediated cytotoxicity
Long-term potentiation
Neurotrophin signaling pathway
Serotonergic synapse
Long-term depression
Regulation of actin cytoskeleton
Insulin signaling pathway
Progesterone-mediated oocyte maturation
Alcoholism
Hepatitis C
Pathways in cancer
Proteoglycans in cancer
Colorectal cancer
Renal cell carcinoma
Pancreatic cancer
Endometrial cancer
Glioma
Prostate cancer
Thyroid cancer
Melanoma
Bladder cancer
Chronic myeloid leukemia
Acute myeloid leukemia
Non-small cell lung cancer
NetPath Pathway IL-7 Signaling Pathway
PANTHER Pathway Angiogenesis
Integrin signalling pathway
Interleukin signaling pathway
PDGF signaling pathway
T cell activation
VEGF signaling pathway
Ras Pathway
CCKR signaling map ST
Pathway Interaction Database CDC42 signaling events
mTOR signaling pathway
Ras signaling in the CD4+ TCR pathway
ErbB1 downstream signaling
PDGFR-beta signaling pathway
Signaling events mediated by VEGFR1 and VEGFR2
Trk receptor signaling mediated by the MAPK pathway
PathWhiz Pathway Intracellular Signalling Through Adenosine Receptor A2a and Adenosine
Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
Reactome Spry regulation of FGF signaling
Frs2-mediated activation
ARMS-mediated activation
CREB phosphorylation through the activation of Ras
RAF activation
MAP2K and MAPK activation
Negative feedback regulation of MAPK pathway
Negative regulation of MAPK pathway
WikiPathways Serotonin Receptor 4/6/7 and NR3C Signaling
Serotonin HTR1 Group and FOS Pathway
Estrogen signaling pathway
Senescence and Autophagy in Cancer
Regulation of Actin Cytoskeleton
EGF/EGFR Signaling Pathway
MAPK Cascade
MAPK Signaling Pathway
Focal Adhesion
Bladder Cancer
Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell
Polycystic Kidney Disease Pathway
Corticotropin-releasing hormone
B Cell Receptor Signaling Pathway
Signaling Pathways in Glioblastoma
TSH signaling pathway
Integrated Breast Cancer Pathway
Signaling by FGFR
NGF signalling via TRKA from the plasma membrane
Integrin-mediated Cell Adhesion
References
Ref 523074ClinicalTrials.gov (NCT01143753) A Study of RO5212054 (PLX3603) in Patients With BRAF V600-mutated Advanced Solid Tumours. U.S. National Institutes of Health.
Ref 523220ClinicalTrials.gov (NCT01225536) Dose Escalation Study of ARQ 736 in Adult Subjects With Advanced Solid Tumors Harboring BRAF and/or NRAS Mutations. U.S. National Institutes of Health.
Ref 524329ClinicalTrials.gov (NCT01877811) CEP-32496 in Patients With Advanced Solid Tumors in Phase 1 and Advanced Melanoma and Metastatic Colorectal Cancer in Phase 2. U.S. National Institutes of Health.
Ref 524363ClinicalTrials.gov (NCT01898585) An Open-Label Study of Zelboraf (Vemurafenib) in Patients With Braf V600 Mutation Positive Metastatic Melanoma. U.S. National Institutes of Health.
Ref 524517ClinicalTrials.gov (NCT01981187) LGX818 for Patients With BRAFV600 Mutated Tumors. U.S. National Institutes of Health.
Ref 525176ClinicalTrials.gov (NCT02428712) A Study of PLX8394 as a Single Agent in Patients With Advanced, Unresectable Solid Tumors. U.S. National Institutes of Health.
Ref 541191(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: 5893).
Ref 542805(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: 7880).
Ref 542830(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: 7908).
Ref 542884(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: 7968).
Ref 548158Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022593)
Ref 549516Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800039268)
Ref 550635Clinical pipeline report, company report or official report of Exelixis (2011).
Ref 550960Clinical pipeline report, company report or official report of GlaxoSmithKline (2011).
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref
Ref 532568Identification of PLX4032-resistance mechanisms and implications for novel RAF inhibitors. Pigment Cell Melanoma Res. 2014 Mar;27(2):253-62.
Ref 533295BGB-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.
Ref 533309First-in-Man Dose-Escalation Study of the Selective BRAF Inhibitor RG7256 in Patients with BRAF V600-Mutated Advanced Solid Tumors. Target Oncol. 2015 Aug 27.
Ref 541025(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).
Ref 543161(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).
Ref 550245Clinical pipeline report, company report or official report of Ambit Biosciences.
Ref 550461National Cancer Institute Drug Dictionary (drug id 680347).
Ref 550466National Cancer Institute Drug Dictionary (drug id 688029).
Ref 550635Clinical pipeline report, company report or official report of Exelixis (2011).
Ref 550960Clinical pipeline report, company report or official report of GlaxoSmithKline (2011).
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 1572591Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
Ref 1587926URL: https://www.ebi.ac.uk/chembl/ The ChEMBL database in 2017

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