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Target not currently curated in GtoImmuPdb
Target id: 1818
Nomenclature: neurotrophic receptor tyrosine kinase 2
Abbreviated Name: trkB
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 1 | 822 | 9q21.33 | NTRK2 | neurotrophic receptor tyrosine kinase 2 | |
Mouse | 1 | 821 | 13 31.2 cM | Ntrk2 | neurotrophic tyrosine kinase, receptor, type 2 | |
Rat | 1 | 821 | 17p14 | Ntrk2 | neurotrophic receptor tyrosine kinase 2 |
Database Links | |
Alphafold | Q16620 (Hs), P15209 (Mm), Q63604 (Rn) |
BRENDA | 2.7.10.1 |
CATH/Gene3D | 2.60.40.10, 3.80.10.10 |
ChEMBL Target | CHEMBL4898 (Hs), CHEMBL4523190 (Mm), CHEMBL1795111 (Rn) |
Ensembl Gene | ENSG00000148053 (Hs), ENSMUSG00000055254 (Mm), ENSRNOG00000018839 (Rn) |
Entrez Gene | 4915 (Hs), 18212 (Mm), 25054 (Rn) |
Human Protein Atlas | ENSG00000148053 (Hs) |
KEGG Enzyme | 2.7.10.1 |
KEGG Gene | hsa:4915 (Hs), mmu:18212 (Mm), rno:25054 (Rn) |
OMIM | 600456 (Hs) |
Orphanet | ORPHA363263 (Hs) |
Pharos | Q16620 (Hs) |
RefSeq Nucleotide | NM_001007097 (Hs), NM_001025074 (Mm), NM_001163168 (Rn) |
RefSeq Protein | NP_001007098 (Hs), NP_001020245 (Mm), NP_032771 (Mm), NP_036863 (Rn) |
SynPHARM | 83183 (in complex with GW-2580) |
UniProtKB | Q16620 (Hs), P15209 (Mm), Q63604 (Rn) |
Wikipedia | NTRK2 (Hs) |
Selected 3D Structures | |||||||||||
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Enzyme Reaction | ||||
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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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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. http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan Reference: 5,22 |
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Target used in screen: TRKB | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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: 2,7 |
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Target used in screen: TrkB/TRKB | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
Immuno Process Associations | ||
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Clinically-Relevant Mutations and Pathophysiology | ||||||||||||
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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. 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. 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]
7. 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]
8. 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]
9. 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]
10. 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]
11. Ito T, Kinoshita K, Tomizawa M, Shinohara S, Nishii H, Matsushita M, Hattori K, Kohchi Y, Kohchi M, Hayase T et al.. (2022) Discovery of CH7057288 as an Orally Bioavailable, Selective, and Potent pan-TRK Inhibitor. J Med Chem, 65 (18): 12427-12444. [PMID:36066182]
12. 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]
13. 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.
14. 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]
15. 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]
16. Li Z, Hu Y, Wei W, Liguang D, Xiaowei D, Yanqing Y, Yinghui S, Yongxin H, Yong P, Fansheng K. (2018) Amino pyrazolopyrimidine compound used as neurotrophic factor tyrosine kinase receptor inhibitor. Patent number: WO2018077246A1. Assignee: Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Beijing Sailintai Pharmaceutical Technology Co., Ltd., Lianyungang Runzhong Pharmaceutical Co., Ltd.. Priority date: 27/10/2017. Publication date: 03/05/2018.
17. 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.
18. 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]
19. Roa P, Foglizzo V, Harada G, Repetto M, Kulick A, de Stanchina E, de Marchena M, Auwardt S, Sayed Ahmed S, Bremer NV et al.. (2024) Zurletrectinib is a next-generation TRK inhibitor with strong intracranial activity against NTRK fusion-positive tumours with on-target resistance to first-generation agents. Br J Cancer, 131 (3): 601-610. [PMID:38902532]
20. 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]
21. 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]
22. 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]
Type VII RTKs: Neurotrophin receptor/Trk family: neurotrophic receptor tyrosine kinase 2. Last modified on 18/07/2024. Accessed on 08/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1818.