Target Information
| Target General Information | Top | |||||
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| Target ID |
T99089
(Former ID: TTDS00346)
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| Target Name |
Serine/threonine-protein kinase B-raf (BRAF)
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| 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
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| Gene Name |
BRAF
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Melanoma [ICD-11: 2C30] | |||||
| 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.
Click to Show/Hide
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.11.1
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| Sequence |
MAALSGGGGGGAEPGQALFNGDMEPEAGAGAGAAASSAADPAIPEEVWNIKQMIKLTQEH
IEALLDKFGGEHNPPSIYLEAYEEYTSKLDALQQREQQLLESLGNGTDFSVSSSASMDTV TSSSSSSLSVLPSSLSVFQNPTDVARSNPKSPQKPIVRVFLPNKQRTVVPARCGVTVRDS LKKALMMRGLIPECCAVYRIQDGEKKPIGWDTDISWLTGEELHVEVLENVPLTTHNFVRK TFFTLAFCDFCRKLLFQGFRCQTCGYKFHQRCSTEVPLMCVNYDQLDLLFVSKFFEHHPI PQEEASLAETALTSGSSPSAPASDSIGPQILTSPSPSKSIPIPQPFRPADEDHRNQFGQR DRSSSAPNVHINTIEPVNIDDLIRDQGFRGDGGSTTGLSATPPASLPGSLTNVKALQKSP GPQRERKSSSSSEDRNRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDV AVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQLAIVTQWCEGSSLYHH LHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATV KSRWSGSHQFEQLSGSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSNIN NRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKRDERPLFPQILASIELLARS LPKIHRSASEPSLNRAGFQTEDFSLYACASPKTPIQAGGYGAFPVH Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T59C5R | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 3 Approved Drugs | + | ||||
| 1 | Dabrafenib | Drug Info | Approved | Melanoma | [2] | |
| 2 | LGX818 | Drug Info | Approved | Melanoma | [3] | |
| 3 | Vemurafenib | Drug Info | Approved | Melanoma | [4], [5], [6] | |
| Clinical Trial Drug(s) | [+] 8 Clinical Trial Drugs | + | ||||
| 1 | PLX8394 | Drug Info | Phase 2 | Solid tumour/cancer | [7] | |
| 2 | BGB-283 | Drug Info | Phase 1/2 | Solid tumour/cancer | [8] | |
| 3 | CEP-32496 | Drug Info | Phase 1/2 | Solid tumour/cancer | [9], [10] | |
| 4 | ABM-1310 | Drug Info | Phase 1 | Solid tumour/cancer | [11] | |
| 5 | ARQ 736 | Drug Info | Phase 1 | Solid tumour/cancer | [12] | |
| 6 | ASN003 | Drug Info | Phase 1 | Solid tumour/cancer | [7] | |
| 7 | BMS-908662 | Drug Info | Phase 1 | Solid tumour/cancer | [13], [14] | |
| 8 | RO-5212054 | Drug Info | Phase 1 | Solid tumour/cancer | [15] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | RG-7256 | Drug Info | Discontinued in Phase 1 | Melanoma | [16] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 11 Inhibitor drugs | + | ||||
| 1 | Dabrafenib | Drug Info | [1], [17] | |||
| 2 | PLX8394 | Drug Info | [19] | |||
| 3 | BGB-283 | Drug Info | [20] | |||
| 4 | CEP-32496 | Drug Info | [21] | |||
| 5 | ABM-1310 | Drug Info | [22] | |||
| 6 | ASN003 | Drug Info | [7] | |||
| 7 | BMS-908662 | Drug Info | [14] | |||
| 8 | RO-5212054 | Drug Info | [24] | |||
| 9 | RG-7256 | Drug Info | [25] | |||
| 10 | AR-00341677 | Drug Info | [26] | |||
| 11 | AZ-628 | Drug Info | [27] | |||
| Modulator | [+] 3 Modulator drugs | + | ||||
| 1 | LGX818 | Drug Info | [18] | |||
| 2 | Vemurafenib | Drug Info | [5] | |||
| 3 | ARQ 736 | Drug Info | [23] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Drug Resistance Mutation (DRM) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Clinical pipeline report, company report or official report of GlaxoSmithKline (2011). | |||||
| REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 3 | 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89. | |||||
| REF 4 | 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: 5893). | |||||
| REF 5 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 6 | ClinicalTrials.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 7 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 8 | ClinicalTrials.gov (NCT03905148) Study of the Safety and Pharmacokinetics of BGB-283 (Lifirfenib) and PD-0325901 (Mirdametinib) in Participants With Advanced or Refractory Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 9 | 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: 7880). | |||||
| REF 10 | ClinicalTrials.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 11 | ClinicalTrials.gov (NCT04190628) Safety of ABM-1310 Monotherapy in Patients With Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 12 | ClinicalTrials.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 13 | 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: 7968). | |||||
| REF 14 | Clinical pipeline report, company report or official report of Exelixis (2011). | |||||
| REF 15 | ClinicalTrials.gov (NCT01143753) A Study of RO5212054 (PLX3603) in Patients With BRAF V600-mutated Advanced Solid Tumours. U.S. National Institutes of Health. | |||||
| REF 16 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022593) | |||||
| REF 17 | Caspase inhibitors: a review of recently patented compounds (2013-2015).Expert Opin Ther Pat. 2018 Jan;28(1):47-59. | |||||
| REF 18 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
| REF 19 | Identification of PLX4032-resistance mechanisms and implications for novel RAF inhibitors. Pigment Cell Melanoma Res. 2014 Mar;27(2):253-62. | |||||
| REF 20 | 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. | |||||
| REF 21 | Clinical pipeline report, company report or official report of Ambit Biosciences. | |||||
| REF 22 | Clinical pipeline report, company report or official report of ABM Therapeutics. | |||||
| REF 23 | National Cancer Institute Drug Dictionary (drug id 688029). | |||||
| REF 24 | National Cancer Institute Drug Dictionary (drug id 680347). | |||||
| REF 25 | 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. | |||||
| REF 26 | 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). | |||||
| REF 27 | 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). | |||||
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