6kzc: Difference between revisions
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==crystal structure of TRKc in complex with 3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-2-methyl-N-(3-((4- methylpiperazin-1-yl)methyl)-5- (trifluoromethyl)phenyl)benzamide== | |||
<StructureSection load='6kzc' size='340' side='right'caption='[[6kzc]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6kzc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KZC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KZC FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DZC:3-(2-imidazo[1,2-a]pyrazin-3-ylethynyl)-2-methyl-~{N}-[3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl]benzamide'>DZC</scene></td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6kzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kzc OCA], [http://pdbe.org/6kzc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kzc RCSB], [http://www.ebi.ac.uk/pdbsum/6kzc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kzc ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/NTRK3_HUMAN NTRK3_HUMAN]] Receptor for neurotrophin-3 (NT-3). This is a tyrosine-protein kinase receptor. Known substrates for the trk receptors are SHC1, PI-3 kinase, and PLCG1. The different isoforms do not have identical signaling properties. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A series of 3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-2-methylbenzamides was designed and synthesized as new tropomyosin receptor kinases (Trks) inhibitors by utilizing a structure-guided optimization strategy. One of the most potent compounds 9o suppressed TrkA/B/C with IC50 values of 2.65, 10.47 and 2.95nM, respectively. The compound dose-dependently inhibited brain-derived neurotrophic factor (BDNF)-mediated TrkB activation and suppressed migration and invasion of SH-SY5Y-TrkB neuroblastoma cells expressing high level of TrkB. Inhibitor 9o also inhibited the proliferation of SH-SY5Y-TrkB cells with an IC50 value of 58nM, which was comparable to that of an US FDA recently approved drug LOXO-101. Compound 9o may serve as a new lead compound for further anti-cancer drug discovery. | |||
Design, synthesis and biological evaluation of 3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-2-methylbenzamides as potent and selective pan-tropomyosin receptor kinase (TRK) inhibitors.,Cui S, Wang Y, Wang Y, Tang X, Ren X, Zhang L, Xu Y, Zhang Z, Zhang ZM, Lu X, Ding K Eur J Med Chem. 2019 Oct 1;179:470-482. doi: 10.1016/j.ejmech.2019.06.064. Epub, 2019 Jun 25. PMID:31271959<ref>PMID:31271959</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6kzc" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Receptor protein-tyrosine kinase]] | |||
[[Category: Wang, Y]] | [[Category: Wang, Y]] | ||
[[Category: Zhang, Z | [[Category: Zhang, Z M]] | ||
[[Category: Transferase]] | |||
[[Category: Trkc]] | |||
Revision as of 05:19, 10 October 2019
crystal structure of TRKc in complex with 3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-2-methyl-N-(3-((4- methylpiperazin-1-yl)methyl)-5- (trifluoromethyl)phenyl)benzamide
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