neurotrophic receptor tyrosine kinase 2

Target id: 1818

Nomenclature: neurotrophic receptor tyrosine kinase 2

Abbreviated Name: trkB

Family: Type VII RTKs: Neurotrophin receptor/Trk family

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for neurotrophic receptor tyrosine kinase 2 in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 477 9q22.1 NTRK2 neurotrophic receptor tyrosine kinase 2
Mouse 1 821 13 Ntrk2 neurotrophic tyrosine kinase, receptor, type 2
Rat 1 821 17p14 Ntrk2 neurotrophic receptor tyrosine kinase 2
Previous and Unofficial Names
BDNF/NT-3 growth factors receptor | Neural receptor protein-tyrosine kinase (trkB) | TRKB1 | neurotrophic tyrosine kinase, receptor, type 2 | neurotrophic tyrosine kinase receptor type 2 | neurotrophic tyrosine kinase
Database Links
BRENDA
CATH/Gene3D
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  The crystal structures of TrkA and TrkB suggest key regions for achieving selective inhibition.
PDB Id:  4ASZ
Resolution:  1.7Å
Species:  Human
References:  4
Image of receptor 3D structure from RCSB PDB
Description:  Ligand binding domain of human TRKB receptor.
PDB Id:  1WWB
Resolution:  2.1Å
Species:  Human
References:  11
Enzyme Reaction
EC Number: 2.7.10.1
Endogenous ligands (Human)
BDNF (BDNF, P23560), neurotrophin-4 (NTF4, P34130) > neurotrophin-3 (NTF3, P20783)

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
GW-2580 Hs Inhibition 7.4 pKd 5
pKd 7.4 (Kd 3.6x10-8 M) [5]
compound 8e [PMID: 24432909] Hs Inhibition 8.4 pIC50 7
pIC50 8.4 (IC50 4x10-9 M) [7]
AZD1332 Hs Inhibition >8.3 pIC50 3
pIC50 >8.3 (IC50 <5x10-9 M) [3]
Description: NIH3T3 cells over expressing TrkB
CEP-11981 Hs Inhibition 8.3 pIC50 8
pIC50 8.3 (IC50 5x10-9 M) [8]
GNF-5837 Hs Inhibition 8.1 pIC50 1
pIC50 8.1 (IC50 9x10-9 M) [1]
MK-2461 Hs Inhibition 7.2 pIC50 10
pIC50 7.2 (IC50 6.1x10-8 M) [10]
DiscoveRx KINOMEscan® screen
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: 5,12

Key to terms and symbols Click column headers to sort
Target used in screen: TRKB
Ligand Sp. Type Action Affinity Units
staurosporine Hs Inhibitor Inhibition 8.4 pKd
foretinib Hs Inhibitor Inhibition 8.4 pKd
lestaurtinib Hs Inhibitor Inhibition 7.8 pKd
GW-2580 Hs Inhibitor Inhibition 7.4 pKd
crizotinib Hs Inhibitor Inhibition 7.4 pKd
JNJ-28312141 Hs Inhibitor Inhibition 6.9 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.9 pKd
KW-2449 Hs Inhibitor Inhibition 6.8 pKd
AST-487 Hs Inhibitor Inhibition 6.7 pKd
tozasertib 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
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: 2,6

Key to terms and symbols Click column headers to sort
Target used in screen: TrkB/TRKB
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 0.4 14.5 -6.0
Gö 6976 Hs Inhibitor Inhibition 0.8 44.0 -12.0
indirubin derivative E804 Hs Inhibitor Inhibition 1.6 -2.0 0.0
K-252a Hs Inhibitor Inhibition 2.1 0.0 0.0
aminopurvalanol A Hs Inhibitor Inhibition 3.0 10.0 1.0
indirubin-3'-monoxime Hs Inhibitor Inhibition 4.1 0.0 0.0
GSK-3 inhibitor XIII Hs Inhibitor Inhibition 4.4 1.0 0.0
Syk inhibitor Hs Inhibitor Inhibition 4.8 23.0 -12.0
dovitinib Hs Inhibitor Inhibition 5.7
SB 218078 Hs Inhibitor Inhibition 6.9 19.0 14.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Obesity, hyperphagia, and developmental delay; OBHD
OMIM: 613886
Disease:  Pilocytic astrocytoma
Disease Ontology: DOID:4851
Orphanet: ORPHA251612
References:  9

References

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1. Albaugh P, Fan Y, Mi Y, Sun F, Adrian F, Li N, Jia Y, Sarkisova Y, Kreusch A, Hood T et al.. (2012) Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models. ACS Med Chem Lett3 (2): 140-5. [PMID:24900443]

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. AstraZeneca. AZD1332. Accessed on 11/09/2014. Modified on 11/09/2014. AstraZeneca.com, http://openinnovation.astrazeneca.com/what-we-offer/compound/azd1332/

4. Bertrand T, Kothe M, Liu J, Dupuy A, Rak A, Berne PF, Davis S, Gladysheva T, Valtre C, Crenne JY et al.. (2012) The crystal structures of TrkA and TrkB suggest key regions for achieving selective inhibition. J. Mol. Biol.423 (3): 439-53. [PMID:22902478]

5. 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]

6. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem. J.451 (2): 313-28. [PMID:23398362]

7. Huang Q, Johnson TW, Bailey S, Brooun A, Bunker KD, Burke BJ, Collins MR, Cook AS, Cui JJ, Dack KN et al.. (2014) Design of potent and selective inhibitors to overcome clinical anaplastic lymphoma kinase mutations resistant to crizotinib. J. Med. Chem.57 (4): 1170-87. [PMID:24432909]

8. Hudkins RL, Becknell NC, Zulli AL, Underiner TL, Angeles TS, Aimone LD, Albom MS, Chang H, Miknyoczki SJ, Hunter K et al.. (2012) Synthesis and biological profile of the pan-vascular endothelial growth factor receptor/tyrosine kinase with immunoglobulin and epidermal growth factor-like homology domains 2 (VEGF-R/TIE-2) inhibitor 11-(2-methylpropyl)-12,13-dihydro-2-methyl-8-(pyrimidin-2-ylamino)-4H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one (CEP-11981): a novel oncology therapeutic agent. J. Med. Chem.55 (2): 903-13. [PMID:22148921]

9. Jones DT, Hutter B, Jäger N, Korshunov A, Kool M, Warnatz HJ, Zichner T, Lambert SR, Ryzhova M, Quang DA et al.. (2013) Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nat. Genet.45 (8): 927-32. [PMID:23817572]

10. Pan BS, Chan GK, Chenard M, Chi A, Davis LJ, Deshmukh SV, Gibbs JB, Gil S, Hang G, Hatch H et al.. (2010) MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res.70 (4): 1524-33. [PMID:20145145]

11. Ultsch MH, Wiesmann C, Simmons LC, Henrich J, Yang M, Reilly D, Bass SH, de Vos AM. (1999) Crystal structures of the neurotrophin-binding domain of TrkA, TrkB and TrkC. J. Mol. Biol.290 (1): 149-59. [PMID:10388563]

12. 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]

How to cite this page

Type VII RTKs: Neurotrophin receptor/Trk family: neurotrophic receptor tyrosine kinase 2. Last modified on 30/03/2016. Accessed on 24/11/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1818.