6kzc

<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>

[[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.

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.

 

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== References ==

[[Category: Wang, Y]]

[[Category: Zhang, Z M]]

[[Category: Trkc]]