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neurotrophic receptor tyrosine kinase 1

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Target not currently curated in GtoImmuPdb

Target id: 1817

Nomenclature: neurotrophic receptor tyrosine kinase 1

Abbreviated Name: trkA

Family: Type VII RTKs: Neurotrophin receptor/Trk family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 796 1q23.1 NTRK1 neurotrophic receptor tyrosine kinase 1
Mouse 1 799 3 38.62 cM Ntrk1 neurotrophic tyrosine kinase, receptor, type 1
Rat 1 799 2q34 Ntrk1 neurotrophic receptor tyrosine kinase 1
Previous and Unofficial Names Click here for help
high affinity nerve growth factor receptor | high-affinity, slow-dissociating NGF receptor | MTC | neurotrophic tyrosine kinase | p140-TrkA | Tkr | TRK | tropomyosin-related kinase A
Database Links Click here for help
Alphafold P04629 (Hs), Q3UFB7 (Mm), P35739 (Rn)
BRENDA 2.7.10.1
CATH/Gene3D 3.80.10.10, 2.60.40.10
ChEMBL Target CHEMBL2815 (Hs), CHEMBL4220 (Rn)
DrugBank Target P04629 (Hs)
Ensembl Gene ENSG00000198400 (Hs), ENSMUSG00000028072 (Mm), ENSRNOG00000013953 (Rn)
Entrez Gene 4914 (Hs), 18211 (Mm), 59109 (Rn)
Human Protein Atlas ENSG00000198400 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:4914 (Hs), mmu:18211 (Mm), rno:59109 (Rn)
OMIM 191315 (Hs)
Orphanet ORPHA123961 (Hs)
Pharos P04629 (Hs)
RefSeq Nucleotide NM_001007792 (Hs), NM_001033124 (Mm), NM_021589 (Rn)
RefSeq Protein NP_001007793 (Hs), NP_001028296 (Mm), NP_067600 (Rn)
UniProtKB P04629 (Hs), Q3UFB7 (Mm), P35739 (Rn)
Wikipedia NTRK1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Identification and structure of the nerve growth factor binding site on TrkA.
PDB Id:  1HE7
Resolution:  2.0Å
Species:  Human
References:  32
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the inactive TrkA kinase domain.
PDB Id:  4gt5
Resolution:  2.4Å
Species:  Human
References:  4
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of apo TrkA.
PDB Id:  4F0I
Resolution:  2.3Å
Species:  Human
References:  6
Enzyme Reaction Click here for help
EC Number: 2.7.10.1
Endogenous ligands (Human)
NGF (NGF, P01138) > neurotrophin-3 (NTF3, P20783)

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
DDR1/2 inhibitor 5n Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.0 pKd 36
⤷ pKd 7.0 (Kd 1x10-7 M) [36]
GW-2580 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.2 pKd 10
⤷ pKd 6.2 (Kd 6.3x10-7 M) [10]
zidesamtinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.3 – 7.3 pKi 15
⤷ pKi 6.3 – 7.3 (Ki 5x10-7 – 5x10-8 M) [15]
Description: Inhibitin of WT TRKA
GR-389988 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 9.5 pIC50 20
⤷ pIC50 9.5 (IC50 3x10-10 M) [20]
Description: In a biochemical assay measuring inhibition of peptide substrate phosphorylation by the test compound in the presence ot recombinant human TrkA.
zurletrectinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.1 – 9.6 pIC50 22,31
⤷ pIC50 9.6 (IC50 2.4x10-10 M) [22]
pIC50 9.1 (IC50 8.1x10-10 M) [31]
selitrectinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition >9.3 pIC50 27
⤷ pIC50 >9.3 (IC50 <5x10-10 M) [27]
repotrectinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.3 pIC50 11
⤷ pIC50 9.3 (IC50 5.3x10-10 M) IC50 for TRKAG595R is 2.7 nM [11]
taletrectinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.2 pIC50 21
⤷ pIC50 9.2 (IC50 6.2x10-10 M) [21]
emzeltrectinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition >9.0 pIC50 25
⤷ pIC50 >9.0 (IC50 <1x10-9 M) [25]
gilteritinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition ~9.0 pIC50 23
⤷ pIC50 ~9.0 (IC50 ~1.1x10-9 M) [23]
anizatrectinib Small molecule or natural product Hs Inhibition 9.0 pIC50 2
⤷ pIC50 9.0 (IC50 1.1x10-9 M) [2]
Description: Binding activity was determined in a TrkA LanthaScreen™ Eu kinase binding assay
CH7057288 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.9 pIC50 19
⤷ pIC50 8.9 (IC50 1.2x10-9 M) [19]
compound 2c [PMID: 24900538] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.9 pIC50 35
⤷ pIC50 8.9 (IC50 1.4x10-9 M) [35]
compound 1d [PMID: 21493067] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pIC50 34
⤷ pIC50 8.5 (IC50 3x10-9 M) [34]
CEP-11981 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pIC50 16
⤷ pIC50 8.5 (IC50 3x10-9 M) [16]
utatrectinib Small molecule or natural product Hs Inhibition 8.5 pIC50 9
⤷ pIC50 8.5 (IC50 3x10-9 M) [9]
Description: In an Alphascreen assay using intracellular domain of a HIS-tagged human Trk A kinase (amino acids 442-796).
AZD1332 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition >8.3 pIC50 5
⤷ pIC50 >8.3 (IC50 <5x10-9 M) [5]
Description: NIH3T3 cells over expressing TrkA
sitravatinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.3 pIC50 30
⤷ pIC50 8.3 (IC50 5x10-9 M) [30]
Description: In a biochemical enzyme activity assay.
larotrectinib Small molecule or natural product Approved drug Hs Inhibition 8.0 pIC50 14
⤷ pIC50 8.0 (IC50 9.7x10-9 M) [14]
Description: Measured using a TrkA ELISA.
paltimatrectinib Small molecule or natural product Hs Inhibition >8.0 pIC50 28
⤷ pIC50 >8.0 (IC50 <1x10-8 M) [28]
GNF-5837 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.0 pIC50 1
⤷ pIC50 8.0 (IC50 1.1x10-8 M) [1]
K-252a Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.9 pIC50 17
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [17]
JNJ-28312141 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.8 pIC50 26
⤷ pIC50 7.8 (IC50 1.5x10-8 M) [26]
RIPK1 inhibitor 22b Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 24
⤷ pIC50 7.6 (IC50 2.6x10-8 M) [24]
MK-2461 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pIC50 29
⤷ pIC50 7.3 (IC50 4.6x10-8 M) [29]
milciclib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pIC50 7
⤷ pIC50 7.3 (IC50 5.3x10-8 M) [7]
CZS-241 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.6 pIC50 33
⤷ pIC50 5.6 (IC50 2.741x10-6 M) [33]
ONO-7579 Small molecule or natural product N/A Inhibition - - 18
⤷ [18]
View species-specific inhibitor tables
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
D5261 Small molecule or natural product Hs Inhibition 5.5 – 5.5 pIC50 13
⤷ pIC50 5.5 (IC50 2.91x10-6 M) [13]
Description: Antiproliferative activity against Ba/F3-CD74-TrkA cells.
pIC50 5.5 (IC50 3.32x10-6 M) [13]
Description: Inhibition of TrkA activity in Ba/F3-MPRIP-TrkA cells.
ponazuril Small molecule or natural product Hs Positive - - 8
⤷ [8]
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: 10,37
Key to terms and symbols Click column headers to sort
Target used in screen: TRKA
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.4 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.3 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.1 pKd
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 7.3 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.0 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 7.0 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.8 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 6.6 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: 3,12
Key to terms and symbols Click column headers to sort
Target used in screen: TrkA/TRKA
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.8 0.0 0.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.6 0.0 -1.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 2.3 0.0 1.0
indirubin derivative E804 Small molecule or natural product Hs Inhibitor Inhibition 3.8 -1.0 0.0
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 4.6
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 5.0 12.0 3.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.9 0.0 -1.0
Syk inhibitor Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 6.1 1.0 1.0
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5
SU11274 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 0.0 2.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  B cell (activation)
Immuno Process:  Immune system development
Immuno Process:  Cellular signalling
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Hereditary sensory and autonomic neuropathy type 5
Synonyms: Hereditary sensory and autonomic neuropathy [Disease Ontology: DOID:11533]
Disease Ontology: DOID:11533
Orphanet: ORPHA64752
Disease:  Insensitivity to pain, congenital, with anhidrosis; CIPA
Synonyms: Hereditary sensory and autonomic neuropathy [Disease Ontology: DOID:11533]
Hereditary sensory and autonomic neuropathy type 4 [Orphanet: ORPHA642]
Disease Ontology: DOID:11533
OMIM: 256800
Orphanet: ORPHA642
Disease:  Thyroid carcinoma, familial medullary
Synonyms: Familial medullary thyroid carcinoma [Disease Ontology: DOID:0050547]
Disease Ontology: DOID:0050547
OMIM: 155240
Orphanet: ORPHA99361
Disease:  Thyroid carcinoma, papillary
Synonyms: Differentiated thyroid carcinoma [Orphanet: ORPHA146]
Papillary thyroid carcinoma [Disease Ontology: DOID:3969]
Disease Ontology: DOID:3969
OMIM: 188550
Orphanet: ORPHA146

References

Show »

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2. Allen S, Andrews SW, Baer B, Crane Z, Liu W, Watson DJ. (2015) 1-((3s,4r)-4-(3-fluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl)-3-(4-methyl-3-(2-methylpyrimidin-5-yl)-1-phenyl-1h-pyrazol-5-yl)urea as a trka kinase inhibitor. Patent number: WO2015175788A1. Assignee: Array Biopharma Inc.. Priority date: 15/05/2014. Publication date: 19/11/2015.

3. 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]

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Type VII RTKs: Neurotrophin receptor/Trk family: neurotrophic receptor tyrosine kinase 1. Last modified on 18/07/2024. Accessed on 10/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1817.