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A-Raf proto-oncogene, serine/threonine kinase

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Target id: 1933

Nomenclature: A-Raf proto-oncogene, serine/threonine kinase

Abbreviated Name: A-Raf

Family: RAF family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 606 Xp11.3 ARAF A-Raf proto-oncogene, serine/threonine kinase
Mouse - 604 X 16.3 cM Araf Araf proto-oncogene, serine/threonine kinase
Rat - 604 Xq11 Araf A-Raf proto-oncogene, serine/threonine kinase
Previous and Unofficial Names Click here for help
ARAF1 | proto-oncogene A-Raf-1 | Raf related protein | Ras-binding protein | A-Raf proto-oncogene | Araf proto-oncogene, serine/threonine kinase | Araf proto-oncogene
Database Links Click here for help
Alphafold P10398 (Hs), P04627 (Mm), P14056 (Rn)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL1169596 (Hs)
Ensembl Gene ENSG00000078061 (Hs), ENSMUSG00000001127 (Mm), ENSRNOG00000010838 (Rn)
Entrez Gene 369 (Hs), 11836 (Mm), 64363 (Rn)
Human Protein Atlas ENSG00000078061 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:369 (Hs), mmu:11836 (Mm), rno:64363 (Rn)
OMIM 311010 (Hs)
Pharos P10398 (Hs)
RefSeq Nucleotide NM_001256196 (Hs), NM_009703 (Mm), NM_022532 (Rn)
RefSeq Protein NP_001645 (Hs), NP_033833 (Mm), NP_071977 (Rn)
UniProtKB P10398 (Hs), P04627 (Mm), P14056 (Rn)
Wikipedia ARAF (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Solution structure of the N-terminal Ras-binding domain (RBD) in human a-Raf kinase.
PDB Id:  1WXM
Resolution:  0.0Å
Species:  Human
References: 
Enzyme Reaction Click here for help
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
exarafenib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.6 pIC50 2
⤷ pIC50 8.6 (IC50 2.4x10-9 M) [2]
lifirafenib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.3 pIC50 4
⤷ pIC50 8.3 (IC50 5.6x10-9 M) [4]
LY3009120 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pIC50 3
⤷ pIC50 7.4 (IC50 4.4x10-8 M) [3]
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
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
Key to terms and symbols Click column headers to sort
Target used in screen: nd/ARAF
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
sorafenib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.0
SB202190 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 31.1
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 33.8
PD 169316 Small molecule or natural product Hs Inhibitor Inhibition 39.1
PKR inhibitor, negative control Small molecule or natural product Hs Inhibitor Inhibition 39.8
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 42.7
p38 MAP kinase inhibitor Small molecule or natural product Hs Inhibitor Inhibition 49.8
Lck inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 53.0
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 55.6
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 57.3
Displaying the top 10 most potent ligands  View all ligands in screen »

References

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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. 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

3. 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]

4. Tang Z, Yuan X, Du R, Cheung SH, Zhang G, Wei J, Zhao Y, Feng Y, Peng H, Zhang Y et al.. (2015) BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF-Mutated Colorectal Cancers. Mol Cancer Ther, 14 (10): 2187-97. [PMID:26208524]

How to cite this page

RAF family: A-Raf proto-oncogene, serine/threonine kinase. Last modified on 17/01/2024. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1933.