6hp9
From Proteopedia
(Difference between revisions)
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==Structure of the kinase domain of human DDR1 in complex with a 2-Amino-2,3-Dihydro-1H-Indene-5-Carboxamide-based inhibitor== | ==Structure of the kinase domain of human DDR1 in complex with a 2-Amino-2,3-Dihydro-1H-Indene-5-Carboxamide-based inhibitor== | ||
| - | <StructureSection load='6hp9' size='340' side='right' caption='[[6hp9]], [[Resolution|resolution]] 1.96Å' scene=''> | + | <StructureSection load='6hp9' size='340' side='right'caption='[[6hp9]], [[Resolution|resolution]] 1.96Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6hp9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HP9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HP9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6hp9]] 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=6HP9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HP9 FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GKB:(2~{R})-~{N}-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-2-(pyrimidin-5-ylamino)-2,3-dihydro-1~{H}-indene-5-carboxamide'>GKB</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GKB:(2~{R})-~{N}-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-2-(pyrimidin-5-ylamino)-2,3-dihydro-1~{H}-indene-5-carboxamide'>GKB</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=6hp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hp9 OCA], [http://pdbe.org/6hp9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hp9 RCSB], [http://www.ebi.ac.uk/pdbsum/6hp9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hp9 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=6hp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hp9 OCA], [http://pdbe.org/6hp9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hp9 RCSB], [http://www.ebi.ac.uk/pdbsum/6hp9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hp9 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Pancreatic cancer is a leading cause of cancer-related death. A series of 2-amino-2, 3-dihydro-1H-indene-5-carboxamide derivatives were designed and synthesized as novel selective DDR1 inhibitors to exhibit promising in vitro and in vivo anti-pancreatic cancer activity. One of the representative compounds, 7f, binds with DDR1 with a Kd value of 5.9 nM and suppresses the kinase activity with an IC50 value of 14.9 nM, but is significantly less potent for majority of a panel of 403 wild-type kinases. The compound potently inhibited collagen-induced epithelial-mesenchymal transition (EMT) and dose-dependently suppressed colony formation of pancreatic cancer cells. Furthermore, 7f also demonstrated reasonable pharmacokinetic profiles and displayed promising in vivo therapeutic efficacy in an orthotopic mouse model of pancreatic cancer. Compound 7f may serve as a new lead compound for future drug discovery. | ||
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| + | 2-Amino-2, 3-Dihydro-1H-Indene-5-Carboxamide-Based Discoidin Domain Receptors 1 (DDR1) Inhibitors: Design, Synthesis, and In Vivo Anti-pancreatic Cancer Efficacy.,Zhu D, Huang H, Pinkas D, Luo J, Ganguly D, Fox AE, Arner E, Xiang Q, Tu ZC, Bullock AN, Brekken RA, Ding K, Lu X J Med Chem. 2019 Jul 16. doi: 10.1021/acs.jmedchem.9b00365. PMID:31310125<ref>PMID:31310125</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6hp9" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Epithelial discoidin domain-containing receptor|Epithelial discoidin domain-containing receptor]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Receptor protein-tyrosine kinase]] | [[Category: Receptor protein-tyrosine kinase]] | ||
[[Category: Arrowsmith, C H]] | [[Category: Arrowsmith, C H]] | ||
Revision as of 06:54, 31 July 2019
Structure of the kinase domain of human DDR1 in complex with a 2-Amino-2,3-Dihydro-1H-Indene-5-Carboxamide-based inhibitor
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