Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7S81XQ)

DOT Name Serine/threonine-protein kinase B-raf (BRAF)
Synonyms EC 2.7.11.1; Proto-oncogene B-Raf; p94; v-Raf murine sarcoma viral oncogene homolog B1
Gene Name BRAF
Related Disease
Cardiofaciocutaneous syndrome ( )
Cardiofaciocutaneous syndrome 1 ( )
LEOPARD syndrome 3 ( )
Noonan syndrome 7 ( )
Noonan syndrome ( )
Noonan syndrome with multiple lentigines ( )
Costello syndrome ( )
Anaplastic astrocytoma ( )
UniProt ID
BRAF_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1UWH ; 1UWJ ; 2FB8 ; 2L05 ; 3C4C ; 3D4Q ; 3IDP ; 3II5 ; 3NY5 ; 3OG7 ; 3PPJ ; 3PPK ; 3PRF ; 3PRI ; 3PSB ; 3PSD ; 3Q4C ; 3Q96 ; 3SKC ; 3TV4 ; 3TV6 ; 4CQE ; 4DBN ; 4E26 ; 4E4X ; 4EHE ; 4EHG ; 4FC0 ; 4FK3 ; 4G9C ; 4G9R ; 4H58 ; 4JVG ; 4KSP ; 4KSQ ; 4MBJ ; 4MNE ; 4MNF ; 4PP7 ; 4R5Y ; 4RZV ; 4RZW ; 4WO5 ; 4XV1 ; 4XV2 ; 4XV3 ; 4XV9 ; 4YHT ; 5C9C ; 5CSW ; 5CSX ; 5CT7 ; 5FD2 ; 5HI2 ; 5HID ; 5HIE ; 5ITA ; 5J17 ; 5J18 ; 5J2R ; 5JRQ ; 5JSM ; 5JT2 ; 5VAL ; 5VAM ; 5VR3 ; 5VYK ; 6B8U ; 6CAD ; 6N0P ; 6N0Q ; 6NSQ ; 6NYB ; 6P3D ; 6P7G ; 6PP9 ; 6Q0J ; 6Q0K ; 6Q0T ; 6U2G ; 6U2H ; 6UAN ; 6UUO ; 6V2U ; 6V2W ; 6V34 ; 6XAG ; 6XFP ; 6XLO ; 7K0V ; 7M0T ; 7M0U ; 7M0V ; 7M0W ; 7M0X ; 7M0Y ; 7M0Z ; 7MFD ; 7MFE ; 7MFF ; 7P3V ; 7SHV ; 7ZR0 ; 7ZR5 ; 7ZR6 ; 8C7X ; 8C7Y ; 8DGS ; 8DGT ; 8F7O ; 8F7P
EC Number
2.7.11.1
Pfam ID
PF00130 ; PF07714 ; PF02196
Sequence
MAALSGGGGGGAEPGQALFNGDMEPEAGAGAGAAASSAADPAIPEEVWNIKQMIKLTQEH
IEALLDKFGGEHNPPSIYLEAYEEYTSKLDALQQREQQLLESLGNGTDFSVSSSASMDTV
TSSSSSSLSVLPSSLSVFQNPTDVARSNPKSPQKPIVRVFLPNKQRTVVPARCGVTVRDS
LKKALMMRGLIPECCAVYRIQDGEKKPIGWDTDISWLTGEELHVEVLENVPLTTHNFVRK
TFFTLAFCDFCRKLLFQGFRCQTCGYKFHQRCSTEVPLMCVNYDQLDLLFVSKFFEHHPI
PQEEASLAETALTSGSSPSAPASDSIGPQILTSPSPSKSIPIPQPFRPADEDHRNQFGQR
DRSSSAPNVHINTIEPVNIDDLIRDQGFRGDGGSTTGLSATPPASLPGSLTNVKALQKSP
GPQRERKSSSSSEDRNRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDV
AVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQLAIVTQWCEGSSLYHH
LHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATV
KSRWSGSHQFEQLSGSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSNIN
NRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKRDERPLFPQILASIELLARS
LPKIHRSASEPSLNRAGFQTEDFSLYACASPKTPIQAGGYGAFPVH
Function
Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway. Phosphorylates PFKFB2. May play a role in the postsynaptic responses of hippocampal neurons.
Tissue Specificity Brain and testis.
KEGG Pathway
EGFR tyrosine ki.se inhibitor resistance (hsa01521 )
Endocrine resistance (hsa01522 )
MAPK sig.ling pathway (hsa04010 )
ErbB sig.ling pathway (hsa04012 )
Rap1 sig.ling pathway (hsa04015 )
cAMP sig.ling pathway (hsa04024 )
Chemokine sig.ling pathway (hsa04062 )
FoxO sig.ling pathway (hsa04068 )
mTOR sig.ling pathway (hsa04150 )
Vascular smooth muscle contraction (hsa04270 )
Focal adhesion (hsa04510 )
.tural killer cell mediated cytotoxicity (hsa04650 )
Long-term potentiation (hsa04720 )
Neurotrophin sig.ling pathway (hsa04722 )
Serotonergic sy.pse (hsa04726 )
Long-term depression (hsa04730 )
Regulation of actin cytoskeleton (hsa04810 )
Insulin sig.ling pathway (hsa04910 )
Progesterone-mediated oocyte maturation (hsa04914 )
Parathyroid hormone synthesis, secretion and action (hsa04928 )
Cushing syndrome (hsa04934 )
Alzheimer disease (hsa05010 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Alcoholism (hsa05034 )
Hepatitis C (hsa05160 )
Hepatitis B (hsa05161 )
Pathways in cancer (hsa05200 )
Proteoglycans in cancer (hsa05205 )
Chemical carcinogenesis - reactive oxygen species (hsa05208 )
Colorectal cancer (hsa05210 )
Re.l cell carcinoma (hsa05211 )
Pancreatic cancer (hsa05212 )
Endometrial cancer (hsa05213 )
Glioma (hsa05214 )
Prostate cancer (hsa05215 )
Thyroid cancer (hsa05216 )
Melanoma (hsa05218 )
Bladder cancer (hsa05219 )
Chronic myeloid leukemia (hsa05220 )
Acute myeloid leukemia (hsa05221 )
Non-small cell lung cancer (hsa05223 )
Breast cancer (hsa05224 )
Hepatocellular carcinoma (hsa05225 )
Gastric cancer (hsa05226 )
Reactome Pathway
Frs2-mediated activation (R-HSA-170968 )
ARMS-mediated activation (R-HSA-170984 )
Signalling to p38 via RIT and RIN (R-HSA-187706 )
RAF activation (R-HSA-5673000 )
MAP2K and MAPK activation (R-HSA-5674135 )
Negative feedback regulation of MAPK pathway (R-HSA-5674499 )
Negative regulation of MAPK pathway (R-HSA-5675221 )
Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946 )
Signaling by high-kinase activity BRAF mutants (R-HSA-6802948 )
Signaling by BRAF and RAF1 fusions (R-HSA-6802952 )
Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955 )
Signaling downstream of RAS mutants (R-HSA-9649948 )
Signaling by RAF1 mutants (R-HSA-9656223 )
SHOC2 M1731 mutant abolishes MRAS complex function (R-HSA-9726840 )
Gain-of-function MRAS complexes activate RAF signaling (R-HSA-9726842 )
Spry regulation of FGF signaling (R-HSA-1295596 )

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cardiofaciocutaneous syndrome DISZJKSC Definitive Autosomal dominant [1]
Cardiofaciocutaneous syndrome 1 DISV4HQA Definitive Autosomal dominant [2]
LEOPARD syndrome 3 DISL1MTL Definitive Autosomal dominant [3]
Noonan syndrome 7 DISZ0W7B Definitive Autosomal dominant [4]
Noonan syndrome DIS7Q7DN Moderate Autosomal dominant [1]
Noonan syndrome with multiple lentigines DIS014D0 Supportive Autosomal dominant [5]
Costello syndrome DISXVJH3 Disputed Autosomal dominant [1]
Anaplastic astrocytoma DISSBE0K Limited Autosomal dominant [6]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 5 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Vemurafenib DM62UG5 Approved Serine/threonine-protein kinase B-raf (BRAF) increases the response to substance of Vemurafenib. [34]
Dabrafenib DMX6OE3 Approved Serine/threonine-protein kinase B-raf (BRAF) increases the response to substance of Dabrafenib. [35]
PF-04691502 DMS610L Phase 2 Serine/threonine-protein kinase B-raf (BRAF) affects the response to substance of PF-04691502. [36]
Bisphenol A DM2ZLD7 Investigative Serine/threonine-protein kinase B-raf (BRAF) affects the response to substance of Bisphenol A. [37]
CI-1040 DMF3DZX Investigative Serine/threonine-protein kinase B-raf (BRAF) increases the response to substance of CI-1040. [38]
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24 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Serine/threonine-protein kinase B-raf (BRAF). [7]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Serine/threonine-protein kinase B-raf (BRAF). [8]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Serine/threonine-protein kinase B-raf (BRAF). [9]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Serine/threonine-protein kinase B-raf (BRAF). [10]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Serine/threonine-protein kinase B-raf (BRAF). [11]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Serine/threonine-protein kinase B-raf (BRAF). [12]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Serine/threonine-protein kinase B-raf (BRAF). [13]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Serine/threonine-protein kinase B-raf (BRAF). [14]
Niclosamide DMJAGXQ Approved Niclosamide decreases the expression of Serine/threonine-protein kinase B-raf (BRAF). [15]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Serine/threonine-protein kinase B-raf (BRAF). [16]
Diclofenac DMPIHLS Approved Diclofenac affects the expression of Serine/threonine-protein kinase B-raf (BRAF). [13]
Gemcitabine DMSE3I7 Approved Gemcitabine decreases the expression of Serine/threonine-protein kinase B-raf (BRAF). [17]
Sorafenib DMS8IFC Approved Sorafenib decreases the activity of Serine/threonine-protein kinase B-raf (BRAF). [18]
Famotidine DMRL3AB Approved Famotidine decreases the activity of Serine/threonine-protein kinase B-raf (BRAF). [19]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of Serine/threonine-protein kinase B-raf (BRAF). [20]
Tanespimycin DMNLQHK Phase 2 Tanespimycin increases the expression of Serine/threonine-protein kinase B-raf (BRAF). [21]
NVP-AUY922 DMTYXQF Phase 2 NVP-AUY922 decreases the expression of Serine/threonine-protein kinase B-raf (BRAF). [22]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Serine/threonine-protein kinase B-raf (BRAF). [24]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Serine/threonine-protein kinase B-raf (BRAF). [25]
PMID25656651-Compound-5 DMAI95U Patented PMID25656651-Compound-5 decreases the activity of Serine/threonine-protein kinase B-raf (BRAF). [27]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Serine/threonine-protein kinase B-raf (BRAF). [28]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Serine/threonine-protein kinase B-raf (BRAF). [29]
4-hydroxy-2-nonenal DM2LJFZ Investigative 4-hydroxy-2-nonenal decreases the expression of Serine/threonine-protein kinase B-raf (BRAF). [31]
[3H]cAMP DMZRQU7 Investigative [3H]cAMP increases the activity of Serine/threonine-protein kinase B-raf (BRAF). [32]
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⏷ Show the Full List of 24 Drug(s)
5 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Serine/threonine-protein kinase B-raf (BRAF). [23]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Serine/threonine-protein kinase B-raf (BRAF). [26]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Serine/threonine-protein kinase B-raf (BRAF). [26]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid decreases the phosphorylation of Serine/threonine-protein kinase B-raf (BRAF). [30]
Icariside II DM3DB8X Investigative Icariside II decreases the phosphorylation of Serine/threonine-protein kinase B-raf (BRAF). [33]
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References

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