6hp9: Difference between revisions

Latest revision as of 11:35, 24 January 2024

Structure of the kinase domain of human DDR1 in complex with a 2-Amino-2,3-Dihydro-1H-Indene-5-Carboxamide-based inhibitor

Structural highlights

6hp9 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.96Å
Ligands:	GKB
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DDR1_HUMAN

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. 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. J Med Chem. 2019 Jul 16. doi: 10.1021/acs.jmedchem.9b00365. PMID:31310125 doi:https://dx.doi.org/10.1021/acs.jmedchem.9b00365

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OCA

[1] 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. 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. J Med Chem. 2019 Jul 16. doi: 10.1021/acs.jmedchem.9b00365. PMID:31310125 doi:https://dx.doi.org/10.1021/acs.jmedchem.9b00365

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='6hp9' size='340' side='right'caption='[[6hp9]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
 == Structural highlights ==
-<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>
+<table><tr><td colspan='2'>[[6hp9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.96&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='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'>[https://proteopedia.org/fgij/fg.htm?mol=6hp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hp9 OCA], [https://pdbe.org/6hp9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hp9 RCSB], [https://www.ebi.ac.uk/pdbsum/6hp9 PDBsum], [https://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>
+== Function ==
+[https://www.uniprot.org/uniprot/DDR1_HUMAN DDR1_HUMAN]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Receptor protein-tyrosine kinase]]
+[[Category: Arrowsmith CH]]
-[[Category: Arrowsmith, C H]]
+[[Category: Bountra C]]
-[[Category: Bountra, C]]
+[[Category: Bullock AN]]
-[[Category: Bullock, A N]]
+[[Category: Burgess-Brown NA]]
-[[Category: Burgess-Brown, N A]]
+[[Category: Edwards AM]]
-[[Category: Delft, F von]]
+[[Category: Fox AE]]
-[[Category: Edwards, A M]]
+[[Category: Kupinska K]]
-[[Category: Fox, A E]]
+[[Category: Pinkas DM]]
-[[Category: Kupinska, K]]
+[[Category: Von Delft F]]
-[[Category: Pinkas, D M]]
-[[Category: Structural genomic]]
-[[Category: Ddr1]]
-[[Category: Sgc]]
-[[Category: Transferase]]

6hp9: Difference between revisions

Latest revision as of 11:35, 24 January 2024

Structure of the kinase domain of human DDR1 in complex with a 2-Amino-2,3-Dihydro-1H-Indene-5-Carboxamide-based inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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