neurotrophic receptor tyrosine kinase 3 | Type VII RTKs: Neurotrophin receptor/Trk family | IUPHAR Guide to IMMUNOPHARMACOLOGY

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neurotrophic receptor tyrosine kinase 3

Target not currently curated in GtoImmuPdb

Target id: 1819

Nomenclature: neurotrophic receptor tyrosine kinase 3

Abbreviated Name: trkC

Family: Type VII RTKs: Neurotrophin receptor/Trk family

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 612 15q24-q25 NTRK3 neurotrophic receptor tyrosine kinase 3
Mouse 1 825 7 Ntrk3 neurotrophic tyrosine kinase
Rat 1 864 1q31 Ntrk3 neurotrophic receptor tyrosine kinase 3
Previous and Unofficial Names
GP145-TrkC | NT-3 growth factor receptor | neural receptor protein-tyrosine kinase (trkC) | neurotrophic tyrosine kinase
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  NT3 binding domain of human TRKC receptor.
Resolution:  1.9Å
Species:  Human
References:  12
Image of receptor 3D structure from RCSB PDB
Description:  Discovery of a selective TRK Inhibitor with efficacy in rodent cancer tumor models: X-Ray diffraction with resolution of 2.20 Å
PDB Id:  3V5Q
Resolution:  2.2Å
Species:  Human
References:  1
Enzyme Reaction
EC Number:
Natural/Endogenous Ligands
neurotrophin-3 {Sp: Human}

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

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
DDR1/2 inhibitor 5n Hs Inhibition 8.0 pKd 13
pKd 8.0 (Kd 9.3x10-9 M) [13]
GW-2580 Hs Inhibition 6.9 pKd 4
pKd 6.9 (Kd 1.2x10-7 M) [4]
repotrectinib Hs Inhibition 9.7 pIC50 5
pIC50 9.7 (IC50 2.1x10-10 M) IC50 for TRKCG623R is 4.5 nM. [5]
GR-389988 Hs Inhibition 9.3 pIC50 7
pIC50 9.3 (IC50 5x10-10 M) [7]
Description: In an off-chip mobility shift assay measuring inhibition of peptide substrate phosphorylation by the test compound in the presence ot recombinant human TrkC, catalytic domain [456-825].
DS-6051b Hs Inhibition 9.0 pIC50 8
pIC50 9.0 (IC50 9.8x10-10 M) [8]
selitrectinib Hs Inhibition >8.6 pIC50 10
pIC50 >8.6 (IC50 <2.5x10-9 M) [10]
AZD1332 Hs Inhibition >8.3 pIC50 3
pIC50 >8.3 (IC50 <5x10-9 M) [3]
Description: NIH3T3 cells over expressing TrkC
GNF-5837 Hs Inhibition 8.1 pIC50 1
pIC50 8.1 (IC50 7x10-9 M) [1]
RIPK1 inhibitor 22b Hs Inhibition 8.1 pIC50 9
pIC50 8.1 (IC50 7x10-9 M) [9]
NIK inhibitor 12f Hs Inhibition 7.3 pIC50 15
pIC50 7.3 (IC50 5.01x10-8 M) [15]
Description: Inhibitory concentration determined in a Reaction Biology kinase sreening assay.
pexidartinib Hs Inhibition 6.1 pIC50 11
pIC50 6.1 (IC50 8.9x10-7 M) [11]
ONO-7579 N/A Inhibition - - 6
View species-specific inhibitor tables
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
Reference: 4,14

Key to terms and symbols Click column headers to sort
Target used in screen: TRKC
Ligand Sp. Type Action Value Parameter
foretinib Hs Inhibitor Inhibition 8.5 pKd
lestaurtinib Hs Inhibitor Inhibition 7.8 pKd
staurosporine Hs Inhibitor Inhibition 7.8 pKd
AST-487 Hs Inhibitor Inhibition 7.5 pKd
JNJ-28312141 Hs Inhibitor Inhibition 7.2 pKd
crizotinib Hs Inhibitor Inhibition 7.1 pKd
GW-2580 Hs Inhibitor Inhibition 6.9 pKd
dovitinib Hs Inhibitor Inhibition 6.7 pKd
doramapimod Hs Inhibitor Inhibition 6.7 pKd
tozasertib Hs Inhibitor Inhibition 6.7 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.

Reference: ...2

Key to terms and symbols Click column headers to sort
Target used in screen: nd/TRKC
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
Gö 6976 Hs Inhibitor Inhibition 0.2
staurosporine Hs Inhibitor Inhibition 1.0
indirubin derivative E804 Hs Inhibitor Inhibition 1.0
Syk inhibitor Hs Inhibitor Inhibition 1.2
K-252a Hs Inhibitor Inhibition 1.2
SB 218078 Hs Inhibitor Inhibition 1.4
dovitinib Hs Inhibitor Inhibition 1.5
SU11652 Hs Inhibitor Inhibition 1.9
GSK-3 inhibitor XIII Hs Inhibitor Inhibition 2.0
indirubin-3'-monoxime Hs Inhibitor Inhibition 2.2
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Congenital mesoblastic nephroma
Disease Ontology: DOID:4773
Orphanet: ORPHA2665
Disease:  Fibrosarcoma
Disease Ontology: DOID:3355
Orphanet: ORPHA2030


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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 Lett, 3 (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.,

4. 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]

5. Drilon A, Ou SI, Cho BC, Kim DW, Lee J, Lin JJ, Zhu VW, Ahn MJ, Camidge DR, Nguyen J et al.. (2018) Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations. Cancer Discov, 8 (10): 1227-1236. [PMID:30093503]

6. Iida H, Fujikawa R, Kozaki R, Harada R, Hosokawa Y, Ogawara KI, Ohno T. (2020) Pharmacokinetic-Pharmacodynamic-Efficacy Modeling of ONO-7579, a Novel Pan-Tropomyosin Receptor Kinase Inhibitor, in a Murine Xenograft Tumor Model. J. Pharmacol. Exp. Ther., 373 (3): 361-369. [PMID:32217770]

7. Kane JL Jr, Matthews G, Metz M, Kothe M, Liu J, Scholte A. (2015) Tropomyosin-related kinase (Trk) inhibitors. Patent number: US9174986B2. Assignee: Genzyme Corp.. Priority date: 10/12/2013. Publication date: 03/11/2015.

8. Katayama R, Gong B, Togashi N, Miyamoto M, Kiga M, Iwasaki S, Kamai Y, Tominaga Y, Takeda Y, Kagoshima Y et al.. (2019) The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models. Nat Commun, 10 (1): 3604. [PMID:31399568]

9. Li Y, Xiong Y, Zhang G, Zhang L, Yang W, Yang J, Huang L, Qiao Z, Miao Z, Lin G et al.. (2018) Identification of 5-(2,3-Dihydro-1 H-indol-5-yl)-7 H-pyrrolo[2,3- d]pyrimidin-4-amine Derivatives as a New Class of Receptor-Interacting Protein Kinase 1 (RIPK1) Inhibitors, Which Showed Potent Activity in a Tumor Metastasis Model. J. Med. Chem., 61 (24): 11398-11414. [PMID:30480444]

10. Nanda N, Bilenker JH, Doebele RC, Blake JF, Kolakowski GR, Brandhuber BJ, Andrews SW. (2017) Point mutations in trk inhibitor-resistant cancer and methods relating to the same. Patent number: WO2017075107A1. Assignee: Array Biopharma Inc, Loxo Oncology Inc. Priority date: 26/10/2015. Publication date: 04/05/2017.

11. Tap WD, Wainberg ZA, Anthony SP, Ibrahim PN, Zhang C, Healey JH, Chmielowski B, Staddon AP, Cohn AL, Shapiro GI et al.. (2015) Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor. N. Engl. J. Med., 373 (5): 428-37. [PMID:26222558]

12. 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]

13. Wang Z, Zhang Y, Pinkas DM, Fox AE, Luo J, Huang H, Cui S, Xiang Q, Xu T, Xun Q et al.. (2018) Design, Synthesis, and Biological Evaluation of 3-(Imidazo[1,2- a]pyrazin-3-ylethynyl)-4-isopropyl- N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide as a Dual Inhibitor of Discoidin Domain Receptors 1 and 2. J. Med. Chem., 61 (17): 7977-7990. [PMID:30075624]

14. 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]

15. Zhu Y, Ma Y, Zu W, Song J, Wang H, Zhong Y, Li H, Zhang Y, Gao Q, Kong B et al.. (2020) Identification of N-phenyl-7H-pyrrolo[2,3-d] pyrimidin-4-amine Derivatives as Novel, Potent, and Selective NF-κB Inducing Kinase (NIK) Inhibitors for the Treatment of Psoriasis. J. Med. Chem., [Epub ahead of print]. [PMID:32479083]

How to cite this page

Type VII RTKs: Neurotrophin receptor/Trk family: neurotrophic receptor tyrosine kinase 3. Last modified on 21/08/2020. Accessed on 25/09/2020. IUPHAR/BPS Guide to PHARMACOLOGY,