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B-Raf proto-oncogene, serine/threonine kinase

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Target id: 1943

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

Abbreviated Name: B-Raf

Family: RAF family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 766 7q34 BRAF B-Raf proto-oncogene, serine/threonine kinase
Mouse - 804 6 18.43 cM Braf Braf transforming gene
Rat - 804 4q21-q22 Braf B-Raf proto-oncogene, serine/threonine kinase
Previous and Unofficial Names Click here for help
BRAF1 | Braf2 | v-raf murine sarcoma viral oncogene homolog B1 | v-raf murine sarcoma viral oncogene homolog B | B-Raf proto-oncogene
Database Links Click here for help
Alphafold P15056 (Hs), P28028 (Mm)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL5145 (Hs), CHEMBL2331061 (Mm)
DrugBank Target P15056 (Hs)
Ensembl Gene ENSG00000157764 (Hs), ENSMUSG00000002413 (Mm), ENSRNOG00000010957 (Rn)
Entrez Gene 673 (Hs), 109880 (Mm), 114486 (Rn)
Human Protein Atlas ENSG00000157764 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:673 (Hs), mmu:109880 (Mm), rno:114486 (Rn)
OMIM 164757 (Hs)
Orphanet ORPHA119066 (Hs)
Pharos P15056 (Hs)
RefSeq Nucleotide NM_004333 (Hs), NM_139294 (Mm), XM_231692 (Rn)
RefSeq Protein NP_004324 (Hs), NP_647455 (Mm), XP_231692 (Rn)
SynPHARM 82209 (in complex with AZ628)
83246 (in complex with BGB-283)
81173 (in complex with CHIR-265)
79043 (in complex with dabrafenib)
81065 (in complex with GDC-0879)
83194 (in complex with LY3009120)
81219 (in complex with PLX-4720)
81218 (in complex with PLX-4720)
81311 (in complex with sorafenib)
79553 (in complex with vemurafenib)
UniProtKB P15056 (Hs), P28028 (Mm)
Wikipedia BRAF (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the RBD domain of serine/threonine-protein kinase B-raf from Homo sapiens. Northeast Structural Genomics Consortium Target HR4694F.
PDB Id:  3NY5
Resolution:  1.99Å
Species:  Human
References: 
Image of receptor 3D structure from RCSB PDB
Description:  The complex of wild type B-RAF and BAY439006.
PDB Id:  1UWH
Ligand:  sorafenib
Resolution:  2.95Å
Species:  Human
References:  24
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Human B-raf bound to a DFG-out Inhibitor TAK-632.
PDB Id:  4KSP
Ligand:  TAK-632
Resolution:  2.93Å
Species:  Human
References:  15
Image of receptor 3D structure from RCSB PDB
Description:  BRAF in complex with N-(3-(2-(2-hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methylphenyl)-2-(trifluoromethyl)isonicotinamide (LXH254)
PDB Id:  6N0P
Ligand:  naporafenib
Resolution:  2.37Å
Species:  Human
References:  18
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
naporafenib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.9 pKd 18
⤷ pKd 8.9 (Kd 1.3x10-9 M) [18]
Description: Binding affinity determined using the KinomeScan® platform.
TAK-632 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.8 pKd 15
⤷ pKd 8.8 (Kd 1.6x10-9 M) [15]
Description: Dissociation constant determined using Surface Plasmon Resonance.
agerafenib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.4 pKd 19
⤷ pKd 7.4 (Kd 3.6x10-8 M) [19]
Description: Inhibition of wild type BRAF activity.
PLX-4720 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.5 pKd 6
⤷ pKd 6.5 (Kd 3.3x10-7 M) [6]
compound 2 [PMID: 26061392] Small molecule or natural product Hs Inhibition 6.3 pKd 9
⤷ pKd 6.3 (Kd 4.44x10-7 M) [9]
CHIR-265 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 5.9 pKd 6
⤷ pKd 5.9 (Kd 1.2x10-6 M) [6]
SB590885 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.8 pKi 11
⤷ pKi 9.8 (Ki 1.6x10-10 M) [11]
Description: In a cell-free assay
GDC-0879 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 9.7 – 9.9 pIC50 6,8
⤷ pIC50 9.7 – 9.9 (IC50 1.9x10-10 – 1.3x10-10 M) [6,8]
dabrafenib Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.5 pIC50 13
⤷ pIC50 8.5 (IC50 3.2x10-9 M) [13]
TAK-632 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.1 pIC50 15
⤷ pIC50 8.1 (IC50 8.3x10-9 M) [15]
Description: Biochemical enzyme inhibition assay.
LY3009120 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.0 pIC50 17
⤷ pIC50 8.0 (IC50 9.1x10-9 M) [17]
L779450 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.0 pIC50 21
⤷ pIC50 8.0 (IC50 1x10-8 M) [21]
LUT014 Small molecule or natural product Hs Inhibition 7.9 – 7.9 pIC50 12
⤷ pIC50 7.9 (IC50 1.17x10-8 M) [12]
Description: Inhibition of wild type BRAF
pIC50 7.9 (IC50 1.33x10-8 M) [12]
Description: Inhibition of BRAFV600E mutant kinase
PLX8394 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.8 pIC50 29
⤷ pIC50 7.8 (IC50 1.4x10-8 M) [29]
vemurafenib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.0 – 8.5 pIC50 12,25
⤷ pIC50 8.5 (IC50 2.87x10-9 M) [12]
Description: Inhibition of wild type BRAF
pIC50 7.0 (IC50 1x10-7 M) [25]
belvarafenib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 – 8.1 pIC50 3
⤷ pIC50 8.1 (IC50 7x10-9 M) [3]
Description: In vitro Inhibition of BRAFV600E
pIC50 7.3 (IC50 5.6x10-8 M) [3]
Description: In vitro Inhibition of wild type BRAF
sorafenib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pIC50 26
⤷ pIC50 7.7 (IC50 2.2x10-8 M) [26]
regorafenib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.6 pIC50 28
⤷ pIC50 7.6 (IC50 2.8x10-8 M) [28]
CCT241161 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.5 pIC50 7
⤷ pIC50 7.5 (IC50 3x10-8 M) [7]
lifirafenib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pIC50 22
⤷ pIC50 7.5 (IC50 3.2x10-8 M) [22]
Description: Inhibition of wild type BRAF kinase domain (aa416-766)
CCT196969 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.0 pIC50 7
⤷ pIC50 7.0 (IC50 1x10-7 M) [7]
PLX-4720 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pIC50 23
⤷ pIC50 6.8 (IC50 1.6x10-7 M) [23]
SZM594 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.5 pIC50 4
⤷ pIC50 6.5 (IC50 3.22x10-7 M) [4]
Description: Determined in a Latha screen assay.
tovorafenib Small molecule or natural product Ligand has a PDB structure Hs Inhibition 5.7 pIC50 20
⤷ pIC50 5.7 (IC50 1.895x10-6 M) [20]
GSK329 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition <5.7 pIC50 16
⤷ pIC50 <5.7 (IC50 >2x10-6 M) [16]
AZ628 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition - - 10
⤷ [10]
Inhibitor Comments
See the ChEMBL link on the Summary tab of the ligand page to view additional kinase targets for regorafenib.
CEP-32496 binds BRAFV600E with a Kd of 14nM, which is lower than its affinity for wild type BRAF [19]. Both CCT196969 and CCT241161 inhibit BRAFV600E with increased potency compared to wild-type- IC50 values vs. V600E are 40nM and 15nM respectively [7].
DiscoveRx KINOMEscan® screen Click here for help
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: 6,27
Key to terms and symbols Click column headers to sort
Target used in screen: BRAF
Ligand Sp. Type Action Value Parameter
GDC-0879 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.7 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.2 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.6 pKd
PLX-4720 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.3 pKd
sorafenib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.3 pKd
motesanib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 6.2 pKd
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 6.1 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
Target used in screen: BRAF(V600E)
Ligand Sp. Type Action Value Parameter
GDC-0879 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.7 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.4 pKd
PLX-4720 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.9 pKd
sorafenib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
motesanib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
CHIR-265 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.4 pKd
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 6.4 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 6.3 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
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: ...2
Key to terms and symbols Click column headers to sort
Target used in screen: nd/BRAF
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
PKR inhibitor, negative control Small molecule or natural product Hs Inhibitor Inhibition 10.2
nilotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 11.5
sorafenib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 19.4
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 52.1
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 53.2
JNJ-7706621 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 55.0
SB202190 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 60.5
PD 169316 Small molecule or natural product Hs Inhibitor Inhibition 72.0
EGFR/ErbB-2 inhibitor Small molecule or natural product Hs Inhibitor Inhibition 75.6
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 78.8
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
BRAFV600E- immuno-oncology [1]
Immuno Process Associations
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 5 GO processes, IEA only
GO:0043368 positive T cell selection IMP
GO:0046632 alpha-beta T cell differentiation IMP
click arrow to show/hide IEA associations
GO:0043367 CD4-positive, alpha-beta T cell differentiation IEA
GO:0043369 CD4-positive or CD8-positive, alpha-beta T cell lineage commitment IEA
GO:0045580 regulation of T cell differentiation IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0045580 regulation of T cell differentiation IEA
GO:0050852 T cell receptor signaling pathway IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 7 GO processes, IEA only
GO:0043368 positive T cell selection IMP
GO:0046632 alpha-beta T cell differentiation IMP
click arrow to show/hide IEA associations
GO:0002318 myeloid progenitor cell differentiation IEA
GO:0043367 CD4-positive, alpha-beta T cell differentiation IEA
GO:0043369 CD4-positive or CD8-positive, alpha-beta T cell lineage commitment IEA
GO:0045580 regulation of T cell differentiation IEA
GO:0048538 thymus development IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 6 GO processes, IEA only
GO:0043368 positive T cell selection IMP
GO:0046632 alpha-beta T cell differentiation IMP
click arrow to show/hide IEA associations
GO:0043367 CD4-positive, alpha-beta T cell differentiation IEA
GO:0043369 CD4-positive or CD8-positive, alpha-beta T cell lineage commitment IEA
GO:0045580 regulation of T cell differentiation IEA
GO:0050852 T cell receptor signaling pathway IEA
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Cardiofaciocutaneous syndrome 1; CFC1
Synonyms: Cardiofaciocutaneous syndrome [Orphanet: ORPHA1340]
OMIM: 115150
Orphanet: ORPHA1340
Disease:  Colorectal cancer
Disease Ontology: DOID:9256
OMIM: 114500
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human V600E The oncogenic V600E non-synonymous mutation is a transforming mutation, and accounts for 80% of BRAF mutations in colorectal cancers. 5
Disease:  Craniopharyngioma
Disease Ontology: DOID:3840
Orphanet: ORPHA54595
Disease:  Hairy cell leukemia
Disease Ontology: DOID:285
Orphanet: ORPHA58017
Disease:  Hashimoto-Pritzker syndrome
Orphanet: ORPHA99872
Disease:  LEOPARD syndrome 3; LPRD3
Synonyms: LEOPARD syndrome [Orphanet: ORPHA500] [Disease Ontology: DOID:14291]
Disease Ontology: DOID:14291
OMIM: 613707
Orphanet: ORPHA500
Disease:  Lung cancer
Disease Ontology: DOID:1324
OMIM: 211980
Role:  Mutations in BRAF are associated with lung adenocarcinoma
Disease:  Lymphoma, non-hodgkin, familial
Description: A lymphoma that is characterized as any kind of lymphoma except Hodgkin's lymphoma. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and lethargy.
Synonyms: Non-Hodgkin lymphoma [Disease Ontology: DOID:0060060]
Disease Ontology: DOID:0060060
OMIM: 605027
References:  14
Disease:  Noonan syndrome 7; NS7
Synonyms: Noonan syndrome [Orphanet: ORPHA648] [Disease Ontology: DOID:3490]
Disease Ontology: DOID:3490
OMIM: 613706
Orphanet: ORPHA648
Disease:  Pilocytic astrocytoma
Disease Ontology: DOID:4851
Orphanet: ORPHA251612

References

Show »

1. Adams JL, Smothers J, Srinivasan R, Hoos A. (2015) Big opportunities for small molecules in immuno-oncology. Nat Rev Drug Discov, 14 (9): 603-22. [PMID:26228631]

2. 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]

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. Chen X, Zhuang C, Ren Y, Zhang H, Qin X, Hu L, Fu J, Miao Z, Chai Y, Liu ZG et al.. (2019) Identification of the Raf kinase inhibitor TAK-632 and its analogues as potent inhibitors of necroptosis by targeting RIPK1 and RIPK3. Br J Pharmacol, 176 (12): 2095-2108. [PMID:30825190]

5. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W et al.. (2002) Mutations of the BRAF gene in human cancer. Nature, 417 (6892): 949-54. [PMID:12068308]

6. 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]

7. 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]

8. Hansen JD, Grina J, Newhouse B, Welch M, Topalov G, Littman N, Callejo M, Gloor S, Martinson M, Laird E et al.. (2008) Potent and selective pyrazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett, 18 (16): 4692-5. [PMID:18676143]

9. Horbert R, Pinchuk B, Davies P, Alessi D, Peifer C. (2015) Photoactivatable Prodrugs of Antimelanoma Agent Vemurafenib. ACS Chem Biol, 10 (9): 2099-107. [PMID:26061392]

10. Khazak V, Astsaturov I, Serebriiskii IG, Golemis EA. (2007) Selective Raf inhibition in cancer therapy. Expert Opin Ther Targets, 11 (12): 1587-609. [PMID:18020980]

11. 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]

12. Lacouture ME, Wainberg ZA, Patel AB, Anadkat MJ, Stemmer SM, Shacham-Shmueli E, Medina E, Zelinger G, Shelach N, Ribas A. (2021) Reducing skin toxicities from EGFR inhibitors with topical BRAF inhibitor therapy. Cancer Discov, [Epub ahead of print]. DOI: 10.1158/2159-8290.CD-20-1847 [PMID:33910927]

13. Laquerre S, Arnone M, Moss K, Yang J, Fisher K, Kane-Carson LS, Smitheman K, Ward J, Heidrich B, Rheault T et al. (2009) Abstract B88: A selective Raf kinase inhibitor induces cell death and tumor regression of human cancer cell lines encoding B-RafV600E mutation. Mol Cancer Ther, 8 (12) Meeting Abstract.

14. Lee JW, Yoo NJ, Soung YH, Kim HS, Park WS, Kim SY, Lee JH, Park JY, Cho YG, Kim CJ et al.. (2003) BRAF mutations in non-Hodgkin's lymphoma. Br J Cancer, 89 (10): 1958-60. [PMID:14612909]

15. 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]

16. Patterson JR, Graves AP, Stoy P, Cheung M, Desai TA, Fries H, Gatto Jr GJ, Holt DA, Shewchuk L, Totoritis R et al.. (2021) Identification of Diarylurea Inhibitors of the Cardiac-Specific Kinase TNNI3K by Designing Selectivity Against VEGFR2, p38α, and B-Raf. J Med Chem, 64 (21): 15651-15670. [PMID:34699203]

17. 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]

18. 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]

19. 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]

20. Sun Y, Alberta JA, Pilarz C, Calligaris D, Chadwick EJ, Ramkissoon SH, Ramkissoon LA, Garcia VM, Mazzola E, Goumnerova L et al.. (2017) A brain-penetrant RAF dimer antagonist for the noncanonical BRAF oncoprotein of pediatric low-grade astrocytomas. Neuro-oncology, 19 (6): 774-785. [PMID:28082416]

21. Takle AK, Brown MJ, Davies S, Dean DK, Francis G, Gaiba A, Hird AW, King FD, Lovell PJ, Naylor A et al.. (2006) The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett, 16 (2): 378-81. [PMID:16260133]

22. 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]

23. Tsai J, Lee JT, Wang W, Zhang J, Cho H, Mamo S, Bremer R, Gillette S, Kong J, Haass NK et al.. (2008) Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci USA, 105 (8): 3041-6. [PMID:18287029]

24. Wan PT, Garnett MJ, Roe SM, Lee S, Niculescu-Duvaz D, Good VM, Jones CM, Marshall CJ, Springer CJ, Barford D et al.. (2004) Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell, 116 (6): 855-67. [PMID:15035987]

25. Wang X, Kim J. (2012) Conformation-specific effects of Raf kinase inhibitors. J Med Chem, 55 (17): 7332-41. [PMID:22808911]

26. 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]

27. 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]

28. Zambon A, Niculescu-Duvaz I, Niculescu-Duvaz D, Marais R, Springer CJ. (2012) Small molecule inhibitors of BRAF in clinical trials. Bioorg Med Chem Lett, 22 (2): 789-92. [PMID:22222036]

29. 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]

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RAF family: B-Raf proto-oncogene, serine/threonine kinase. Last modified on 17/11/2021. Accessed on 25/05/2022. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1943.