6gwr
From Proteopedia
(Difference between revisions)
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<StructureSection load='6gwr' size='340' side='right' caption='[[6gwr]], [[Resolution|resolution]] 2.07Å' scene=''> | <StructureSection load='6gwr' size='340' side='right' caption='[[6gwr]], [[Resolution|resolution]] 2.07Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6gwr]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GWR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GWR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6gwr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GWR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GWR FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FEW:3-(2-imidazo[1,2-a]pyrazin-3-ylethynyl)-~{N}-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]-4-propan-2-yl-benzamide'>FEW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FEW:3-(2-imidazo[1,2-a]pyrazin-3-ylethynyl)-~{N}-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]-4-propan-2-yl-benzamide'>FEW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DDR1, CAK, EDDR1, NEP, NTRK4, PTK3A, RTK6, TRKE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='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=6gwr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gwr OCA], [http://pdbe.org/6gwr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gwr RCSB], [http://www.ebi.ac.uk/pdbsum/6gwr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gwr ProSAT]</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=6gwr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gwr OCA], [http://pdbe.org/6gwr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gwr RCSB], [http://www.ebi.ac.uk/pdbsum/6gwr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gwr ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Discoidin domain receptor 1 and 2 (DDR1 and DDR2) are new potential targets for anti-inflammatory drug discovery. A series of heterocycloalkynylbenzimides were designed and optimized to co-inhibit DDR1 and DDR2. One of the most promising compounds, 5n, tightly bound to DDR1 and DDR2 protein with Kd values of 7.9 and 8.0 nM, and potently inhibited the kinases with IC50 values of 9.4 and 20.4 nM, respectively, while was significantly less potent for a panel of 403 wild-type kinases at 1.0 muM. DDR1 and DDR2 kinase inhibition by 5n was validated by Western blotting analysis in primary human lung fibroblasts. The compound also dose-dependently inhibited lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) release in vitro, and exhibited promising in vivo anti-inflammatory effect in a LPS-induced acute lung injury (ALI) mouse model. Compound 5n may serve as a lead compound for new anti-inflammatory drug discovery. | ||
| + | |||
| + | Design, Synthesis and Biological Evaluation of 3-(Imidazo[1,2-a]pyrazin-3-ylethynyl)-4-isopropyl-N-(3-((4-methylpiperazin-1-yl)m ethyl)-5-(trifluoromethyl)phenyl)benzamide as Dual Inhibitors of Discoidin Domain Receptor 1 and 2 (DDR1/2).,Wang Z, Zhang Y, Pinkas D, Fox A, Luo J, Huang H, Cui S, Xiang Q, Xu T, Xun Q, Zhu D, Tu ZC, Ren X, Brekken RA, Bullock AN, Liang G, Ding K, Lu X J Med Chem. 2018 Aug 3. doi: 10.1021/acs.jmedchem.8b01045. PMID:30075624<ref>PMID:30075624</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6gwr" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Receptor protein-tyrosine kinase]] | [[Category: Receptor protein-tyrosine kinase]] | ||
[[Category: Arrowsmith, C H]] | [[Category: Arrowsmith, C H]] | ||
Revision as of 16:43, 15 August 2018
Structure of the kinase domain of human DDR1 in complex with a potent and selective inhibitor of DDR1 and DDR2
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