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Target not currently curated in GtoImmuPdb
Target id: 2184
Nomenclature: Raf-1 proto-oncogene, serine/threonine kinase
Abbreviated Name: c-Raf
Family: RAF family
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 648 | 3p25.2 | RAF1 | Raf-1 proto-oncogene, serine/threonine kinase | |
Mouse | - | 648 | 6 53.62 cM | Raf1 | v-raf-leukemia viral oncogene 1 | |
Rat | - | 648 | 4q42 | Raf1 | Raf-1 proto-oncogene, serine/threonine kinase |
Previous and Unofficial Names |
Raf-1 proto-oncogene | RAF proto-oncogene serine/threonine-protein kinase |
Database Links | |
Alphafold | P04049 (Hs), Q99N57 (Mm), P11345 (Rn) |
BRENDA | 2.7.11.1 |
ChEMBL Target | CHEMBL1906 (Hs), CHEMBL3804748 (Mm) |
DrugBank Target | P04049 (Hs) |
Ensembl Gene | ENSG00000132155 (Hs), ENSMUSG00000000441 (Mm), ENSRNOG00000010153 (Rn) |
Entrez Gene | 5894 (Hs), 110157 (Mm), 24703 (Rn) |
Human Protein Atlas | ENSG00000132155 (Hs) |
KEGG Enzyme | 2.7.11.1 |
KEGG Gene | hsa:5894 (Hs), mmu:110157 (Mm), rno:24703 (Rn) |
OMIM | 164760 (Hs) |
Orphanet | ORPHA138722 (Hs) |
Pharos | P04049 (Hs) |
RefSeq Nucleotide | NM_002880 (Hs), NM_029780 (Mm), NM_012639 (Rn) |
RefSeq Protein | NP_002871 (Hs), NP_084056 (Mm), NP_036771 (Rn) |
UniProtKB | P04049 (Hs), Q99N57 (Mm), P11345 (Rn) |
Wikipedia | RAF1 (Hs) |
Selected 3D Structures | |||||||||||
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Enzyme Reaction | ||||
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Download all structure-activity data for this target as a CSV file
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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DiscoveRx KINOMEscan® screen | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform. http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan Reference: 9,29 |
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Target used in screen: RAF1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service. A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform. http://www.millipore.com/techpublications/tech1/pf3036 http://www.reactionbiology.com/webapps/main/pages/kinase.aspx Reference: 1,12 |
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Target used in screen: c-RAF/RAF1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
Immuno Process Associations | ||
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Clinically-Relevant Mutations and Pathophysiology | ||||||||||||||||||||||||||||||||||||
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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]
2. Aoki T, Hyohdoh I, Furuichi N, Ozawa S, Watanabe F, Matsushita M, Sakaitani M, Morikami K, Takanashi K, Harada N et al.. (2014) Optimizing the Physicochemical Properties of Raf/MEK Inhibitors by Nitrogen Scanning. ACS Med Chem Lett, 5 (4): 309-14. [PMID:24900832]
3. Bae IH, Son JB, Han SM, Kwak EJ, Kim HS, Song JY, Byun EY, Jun SA, Ahn YG, Suh KH. (2013) THIENO[3,2-d]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES. Patent number: WO2013100632A1. Assignee: Hanmi Pharm Co. Priority date: 30/12/2011. Publication date: 04/07/2013.
4. Bain J, McLauchlan H, Elliott M, Cohen P. (2003) The specificities of protein kinase inhibitors: an update. Biochem J, 371 (Pt 1): 199-204. [PMID:12534346]
5. Berger DM, Powell DW, Wu B. (2009) 3-quinolinecarbonitrile protein kinase inhibitors. Patent number: US20090062281A1. Assignee: Wyeth LLC. Priority date: 20/02/2004. Publication date: 05/03/2009.
6. Bouhana K, Anderson D, DeWolf W, Brown S, Williams L, Ren L, Moreno D, Wallace R, Fell JB, Hartley D et al.. (2021) Abstract 1473: Nonclinical development of PF-07284890 (ARRY-461), a potent, brain-penetrant, small molecule inhibitor of BRAF V600-mutation-driven tumors in vitro and in vivo. Cancer Research, 81: 1473. DOI: 10.1158/1538-7445.AM2021-1473
7. Chen YK, Kanouni T, Arnold LD, Cox JM, Gardiner E, Grandinetti K, Jiang P, Kaldor SW, Lee C, Li C et al.. (2024) The Discovery of Exarafenib (KIN-2787): Overcoming the Challenges of Pan-RAF Kinase Inhibition. J Med Chem,. DOI: 10.1021/acs.jmedchem.3c01830
8. Chin PC, Liu L, Morrison BE, Siddiq A, Ratan RR, Bottiglieri T, D'Mello SR. (2004) The c-Raf inhibitor GW5074 provides neuroprotection in vitro and in an animal model of neurodegeneration through a MEK-ERK and Akt-independent mechanism. J Neurochem, 90 (3): 595-608. [PMID:15255937]
9. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]
10. Dolente C, Hewings DS, Hunziker D, Krummenacher D, Pettazzoni PFT, Wichmann J. (2021) New braf inhibitors as paradox breakers. Patent number: WO2021116050A1. Assignee: Hoffmann-La Roche. Priority date: 28/12/2020. Publication date: 17/06/2021.
11. Fedorov O, Marsden B, Pogacic V, Rellos P, Müller S, Bullock AN, Schwaller J, Sundström M, Knapp S. (2007) A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci USA, 104 (51): 20523-8. [PMID:18077363]
12. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]
13. Garton AJ, Crew AP, Franklin M, Cooke AR, Wynne GM, Castaldo L, Kahler J, Winski SL, Franks A, Brown EN et al.. (2006) OSI-930: a novel selective inhibitor of Kit and kinase insert domain receptor tyrosine kinases with antitumor activity in mouse xenograft models. Cancer Res, 66 (2): 1015-24. [PMID:16424037]
14. Girotti MR, Lopes F, Preece N, Niculescu-Duvaz D, Zambon A, Davies L, Whittaker S, Saturno G, Viros A, Pedersen M et al.. (2015) Paradox-breaking RAF inhibitors that also target SRC are effective in drug-resistant BRAF mutant melanoma. Cancer Cell, 27 (1): 85-96. [PMID:25500121]
15. Hart AC, Abell L, Guo J, Mertzman ME, Padmanabha R, Macor JE, Chaudhry C, Lu H, O'Malley K, Shaw PJ et al.. (2019) Identification of RIPK3 Type II Inhibitors Using High-Throughput Mechanistic Studies in Hit Triage. ACS Med Chem Lett, Article ASAP. DOI: 10.1021/acsmedchemlett.9b00065
16. Hatzivassiliou G, Song K, Yen I, Brandhuber BJ, Anderson DJ, Alvarado R, Ludlam MJ, Stokoe D, Gloor SL, Vigers G et al.. (2010) RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature, 464 (7287): 431-5. [PMID:20130576]
17. Jones DT, Kocialkowski S, Liu L, Pearson DM, Ichimura K, Collins VP. (2009) Oncogenic RAF1 rearrangement and a novel BRAF mutation as alternatives to KIAA1549:BRAF fusion in activating the MAPK pathway in pilocytic astrocytoma. Oncogene, 28 (20): 2119-23. [PMID:19363522]
18. Kaldor SW, Kanouni T, Tyhonas J, Murphy EA. (2021) Inhibitors of raf kinases. Patent number: WO2021081375A1. Assignee: Kinnate Biopharma Inc.. Priority date: 24/10/2019. Publication date: 29/04/2021.
19. King AJ, Patrick DR, Batorsky RS, Ho ML, Do HT, Zhang SY, Kumar R, Rusnak DW, Takle AK, Wilson DM et al.. (2006) Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885. Cancer Res, 66 (23): 11100-5. [PMID:17145850]
20. Okaniwa M, Hirose M, Arita T, Yabuki M, Nakamura A, Takagi T, Kawamoto T, Uchiyama N, Sumita A, Tsutsumi S et al.. (2013) Discovery of a selective kinase inhibitor (TAK-632) targeting pan-RAF inhibition: design, synthesis, and biological evaluation of C-7-substituted 1,3-benzothiazole derivatives. J Med Chem, 56 (16): 6478-94. [PMID:23906342]
21. Pandit B, Sarkozy A, Pennacchio LA, Carta C, Oishi K, Martinelli S, Pogna EA, Schackwitz W, Ustaszewska A, Landstrom A et al.. (2007) Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nat Genet, 39 (8): 1007-12. [PMID:17603483]
22. Peng SB, Henry JR, Kaufman MD, Lu WP, Smith BD, Vogeti S, Rutkoski TJ, Wise S, Chun L, Zhang Y et al.. (2015) Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers. Cancer Cell, 28 (3): 384-98. [PMID:26343583]
23. Ramurthy S, Taft BR, Aversa RJ, Barsanti PA, Burger MT, Lou Y, Nishiguchi GA, Rico A, Setti L, Smith A et al.. (2020) Design and Discovery of N-(3-(2-(2-Hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methylphenyl)-2-(trifluoromethyl)isonicotinamide, a Selective, Efficacious, and Well-Tolerated RAF Inhibitor Targeting RAS Mutant Cancers: The Path to the Clinic. J Med Chem, 63 (5): 2013-2027. [PMID:31059256]
24. Razzaque MA, Nishizawa T, Komoike Y, Yagi H, Furutani M, Amo R, Kamisago M, Momma K, Katayama H, Nakagawa M et al.. (2007) Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nat Genet, 39 (8): 1013-7. [PMID:17603482]
25. Rowbottom MW, Faraoni R, Chao Q, Campbell BT, Lai AG, Setti E, Ezawa M, Sprankle KG, Abraham S, Tran L et al.. (2012) Identification of 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea hydrochloride (CEP-32496), a highly potent and orally efficacious inhibitor of V-RAF murine sarcoma viral oncogene homologue B1 (BRAF) V600E. J Med Chem, 55 (3): 1082-105. [PMID:22168626]
26. Ryan MB, Quade B, Schenk N, Fang Z, Zingg M, Cohen SE, Swalm BM, Li C, Özen A, Ye C et al.. (2024) The Pan-RAF-MEK Nondegrading Molecular Glue NST-628 Is a Potent and Brain-Penetrant Inhibitor of the RAS-MAPK Pathway with Activity across Diverse RAS- and RAF-Driven Cancers. Cancer Discov, 14 (7): 1190-1205. [PMID:38588399]
27. Wang X, Kim J. (2012) Conformation-specific effects of Raf kinase inhibitors. J Med Chem, 55 (17): 7332-41. [PMID:22808911]
28. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M et al.. (2004) BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res, 64 (19): 7099-109. [PMID:15466206]
29. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]
30. Zhang C, Spevak W, Zhang Y, Burton EA, Ma Y, Habets G, Zhang J, Lin J, Ewing T, Matusow B et al.. (2015) RAF inhibitors that evade paradoxical MAPK pathway activation. Nature, 526 (7574): 583-6. [PMID:26466569]
31. Zhou C, Zhang G. (2014) Fused tricyclic urea compounds as raf kinase and/or raf kinase dimer inhibitors. Patent number: WO2014206343A1. Assignee: Beigene, Ltd.. Priority date: 27/06/2014. Publication date: 31/12/2014.
32. Zhu T, Jiao Y, Chen YD, Wang X, Li HF, Zhang LY, Lu T. (2008) Pharmacophore identification of Raf-1 kinase inhibitors. Bioorg Med Chem Lett, 18 (7): 2346-50. [PMID:18346893]
RAF family: Raf-1 proto-oncogene, serine/threonine kinase. Last modified on 15/08/2024. Accessed on 18/01/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2184.