General Information of the Protein
Protein ID
PT01390
Protein Name
BDNF/NT-3 growth factors receptor
Secondarily
Protein Name
GP145-TrkB
Neurotrophic tyrosine kinase receptor type 2
TrkB tyrosine kinase
Tropomyosin-related kinase B
Gene Name
NTRK2
Secondarily
Gene Name
TRKB
Sequence
MSSWIRWHGPAMARLWGFCWLVVGFWRAAFACPTSCKCSASRIWCSDPSPGIVAFPRLEPNSVDPENITEIFIANQKRLEIINEDDVEAYVGLRNLTIVDSGLKFVAHKAFLKNSNLQHINFTRNKLTSLSRKHFRHLDLSELILVGNPFTCSCDIMWIKTLQEAKSSPDTQDLYCLNESSKNIPLANLQIPNCGLPSANLAAPNLTVEEGKSITLSCSVAGDPVPNMYWDVGNLVSKHMNETSHTQGSLRITNISSDDSGKQISCVAENLVGEDQDSVNLTVHFAPTITFLESPTSDHHWCIPFTVKGNPKPALQWFYNGAILNESKYICTKIHVTNHTEYHGCLQLDNPTHMNNGDYTLIAKNEYGKDEKQISAHFMGWPGIDDGANPNYPDVIYEDYGTAANDIGDTTNRSNEIPSTDVTDKTGREHLSVYAVVVIASVVGFCLLVMLFLLKLARHSKFGMKGPASVISNDDDSASPLHHISNGSNTPSSSEGGPDAVIIGMTKIPVIENPQYFGITNSQLKPDTFVQHIKRHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMVFEYMKHGDLNKFLRAHGPDAVLMAEGNPPTELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPQEVYELMLGCWQREPHMRKNIKGIHTLLQNLAKASPVYLDILG
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
TK protein kinase group
>
Tyrosine protein kinase Trk family
Function
Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity (By similarity). Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2 (PubMed:7574684, PubMed:15494731). Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:15494731). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia.
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Uniprot ID
Primary ID:
Q16620

Secondarily ID:
B1ANZ4
B4DFV9
Q16675
Q59GJ1
Q8WXJ5
Q8WXJ6
Q8WXJ7
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Ensembl ID
ENSG00000148053
HGNC ID
HGNC:8032
Subcellular Location
Cell membrane
Endosome membrane
Early endosome membrane
Cell projection
Axon
Cell projection
Dendrite
Cytoplasm
Perinuclear region
Postsynaptic density
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000077 , Ba/F3
Compound ID Compound Name Compound Formula
CP0137907
2-(4-methylpiperazin-1-yl)-N-[4-methyl-5-[3-[(E)-2-pyridin-2-ylethenyl]-1H-indazol-6-yl]-1,3-thiazol-2-yl]acetamide
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C25H27N7OS
 2
1
EC50 = 69 nM
   TI
   LI
   LO
   TS
2
GI50 = 8.2 nM
   TI
   LI
   LO
   TS
CP0385508
2-[4-[4-[6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl]pyridin-2-yl]piperazin-1-yl]acetic acid
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C27H28FN7O2
 1
1
IC50 = 1 nM
   TI
   LI
   LO
   TS
CP0395047
6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]-3-pyridin-2-ylimidazo[1,2-b]pyridazine
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C21H18FN5
 1
1
IC50 = 1 nM
   TI
   LI
   LO
   TS
CP0385511
1-[4-[6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl]pyridin-2-yl]piperidin-4-ol
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C26H27FN6O
 1
1
IC50 = 4 nM
   TI
   LI
   LO
   TS
CP0433699
1-[6-[6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl]pyridin-2-yl]piperidin-4-ol
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C26H27FN6O
 1
1
IC50 = 4 nM
   TI
   LI
   LO
   TS
CP0859348
N-[3-(6-{[(3-Fluorophenyl)methyl]amino}imidazo[1,2-b]pyridazin-3-yl)phenyl]oxane-4-carboxamide
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C25H24FN5O2
 1
1
IC50 = 7 nM
   TI
   LI
   LO
   TS
CP0433700
4-[6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl]benzonitrile
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C23H18FN5
 1
1
IC50 = 11 nM
   TI
   LI
   LO
   TS
CP0543110
4-[6-[(3-fluorophenyl)methylamino]imidazo[1,2-b]pyridazin-3-yl]benzenesulfonamide
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C19H16FN5O2S
 1
1
IC50 = 13 nM
   TI
   LI
   LO
   TS
CP0488257
4-[6-[(3-fluorophenyl)methylamino]imidazo[1,2-b]pyridazin-3-yl]benzonitrile
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C20H14FN5
 1
1
IC50 = 21 nM
   TI
   LI
   LO
   TS
CP0510927
[4-[6-[(3-fluorophenyl)methylamino]imidazo[1,2-b]pyridazin-3-yl]phenyl]methanol
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C20H17FN4O
 1
1
IC50 = 27 nM
   TI
   LI
   LO
   TS
CP0530865
4-[6-[2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl]benzonitrile
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C23H18FN5
 1
1
IC50 = 29 nM
   TI
   LI
   LO
   TS
CP0542684
4-[6-[3-(3-fluorophenyl)morpholin-4-yl]imidazo[1,2-b]pyridazin-3-yl]benzonitrile
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C23H18FN5O
 1
1
IC50 = 47 nM
   TI
   LI
   LO
   TS
CP0561248
4-[6-[2-(3-fluorophenyl)piperidin-1-yl]imidazo[1,2-b]pyridazin-3-yl]benzonitrile
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C24H20FN5
 1
1
IC50 = 50 nM
   TI
   LI
   LO
   TS
CP0856137
4-(6-{[(2-Methoxyphenyl)methyl]amino}imidazo[1,2-b]pyridazin-3-yl)benzonitrile
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C21H17N5O
 1
1
IC50 = 120 nM
   TI
   LI
   LO
   TS
CP0510926
4-[6-[benzyl(methyl)amino]imidazo[1,2-b]pyridazin-3-yl]benzonitrile
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C21H17N5
 1
1
IC50 = 130 nM
   TI
   LI
   LO
   TS
CP0922172
3-[6-(Benzylamino)imidazo[1,2-b]pyridazin-3-yl]benzonitrile
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C20H15N5
 1
1
IC50 = 200 nM
   TI
   LI
   LO
   TS
CP0388864
4-[6-(benzylamino)imidazo[1,2-b]pyridazin-3-yl]benzonitrile
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C20H15N5
 1
1
IC50 = 270 nM
   TI
   LI
   LO
   TS
CP0388615
3-(3,4-dimethoxyphenyl)-5-(1-methylpiperidin-4-yl)oxy-6-(1,3-thiazol-2-yl)pyrazolo[1,5-a]pyrimidin-7-amine
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C23H26N6O3S
 1
1
IC50 = 770 nM
   TI
   LI
   LO
   TS
CP0418567
3-[4-amino-7-[3-(hydroxymethyl)cyclobutyl]pyrrolo[2,3-d]pyrimidin-5-yl]phenol
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C17H18N4O2
 1
1
IC50 = 1300 nM
   TI
   LI
   LO
   TS
CP0061016
3-(4-Amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-phenol
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C17H18N4O
 1
1
IC50 = 1400 nM
   TI
   LI
   LO
   TS
CP0395369
4-[6-[(2S)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl]benzonitrile
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C23H18FN5
 1
1
IC50 = 1970 nM
   TI
   LI
   LO
   TS
CP0019908
BDBM50242742
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C30H40ClN7O3S
 1
1
IC50 = 2018 nM
   TI
   LI
   LO
   TS
CP0388620
methyl N-[4-[7-amino-3-(3,4-dimethoxyphenyl)-5-(1-methylpiperidin-4-yl)oxypyrazolo[1,5-a]pyrimidin-6-yl]phenyl]carbamate
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C28H32N6O5
 1
1
IC50 = 2100 nM
   TI
   LI
   LO
   TS
CP0661487
3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea monophosphate
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C26H34Cl2N7O7P
 1
1
IC50 = 3139 nM
   TI
   LI
   LO
   TS
CP0138866
1-[4-[3-[4-amino-5-(2-fluoro-5-hydroxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclobutyl]piperazin-1-yl]ethanone
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C22H25FN6O2
 1
1
IC50 = 8500 nM
   TI
   LI
   LO
   TS
CP0388616
3-(3,4-dimethoxyphenyl)-5-(1-methylpiperidin-4-yl)oxy-6-phenylpyrazolo[1,5-a]pyrimidin-7-amine
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C26H29N5O3
 1
1
IC50 > 11000 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0137907
2-(4-methylpiperazin-1-yl)-N-[4-methyl-5-[3-[(E)-2-pyridin-2-ylethenyl]-1H-indazol-6-yl]-1,3-thiazol-2-yl]acetamide
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C25H27N7OS
 1
1 IC50 = 0.71 nM
CP0020453
US10081622, Compound 11
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C31H34F2N6O2
 3
1 IC50 = 1 nM
2 IC50 = 3 nM
3 IC50 < 10 nM
CP0053535
3-[1-(5-Methoxy-1-methyl-1H-indol-3-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-1H-indole-5-sulfonic acid amide
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C19H17N3O4S
 1
1 IC50 = 3.92 nM
CP0130033
3-[1-(5-Methoxy-1-methyl-1H-indol-3-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-1H-indole-5-sulfonic acid methylamide
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C20H19N3O4S
 1
1 IC50 = 4.52 nM
CP0130019
3-[1-(5-Methoxy-1-methyl-1H-indol-3-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-1H-indole-5-sulfonic acid dimethylamide
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C21H21N3O4S
 1
1 IC50 = 15.25 nM
CP0388864
4-[6-(benzylamino)imidazo[1,2-b]pyridazin-3-yl]benzonitrile
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C20H15N5
 1
1 IC50 = 83 nM
CP0019908
BDBM50242742
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C30H40ClN7O3S
 1
1 Kd = 130 nM
Clinical Information about the Protein
Target 1 ( BDNF/NT-3 growth factors receptor (TrkB) )
Target Type Successful Target
Disease 3 Target-related Diseases  3
1 Non-small-cell lung cancer [ICD-11: 2C25]
2 Alzheimer disease [ICD-11: 8A20]
3 Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Approved Drug(s) 2 Approved Drugs  2
1 Entrectinib Approved
Non-small-cell lung cancer
2 Larotrectinib Approved
Solid tumour/cancer
Clinical Trial Drug(s) 1 Clinical Trial Drug  1
1 MK-2461 Phase 1/2
Alzheimer disease