View source for 5bvw


==Fragment-based discovery of potent and selective DDR1/2 inhibitors==
<StructureSection load='5bvw' size='340' side='right'caption='[[5bvw]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5bvw]] is a 1 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=5BVW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BVW FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1N1:N-(2-CHLORO-6-METHYLPHENYL)-2-({6-[4-(2-HYDROXYETHYL)PIPERAZIN-1-YL]-2-METHYLPYRIMIDIN-4-YL}AMINO)-1,3-THIAZOLE-5-CARBOXAMIDE'>1N1</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></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=5bvw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bvw OCA], [https://pdbe.org/5bvw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bvw RCSB], [https://www.ebi.ac.uk/pdbsum/5bvw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bvw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DDR1_HUMAN DDR1_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The DDR1 and DDR2 receptor tyrosine kinases are activated by extracellular collagen and have been implicated in a number of human diseases including cancer. We performed a fragment-based screen against DDR1 and identified fragments that bound either at the hinge or in the back pocket associated with the DFG-out conformation of the kinase. Modeling based on crystal structures of potent kinase inhibitors facilitated the "back-to-front" design of potent DDR1/2 inhibitors that incorporated one of the DFG-out fragments. Further optimization led to low nanomolar, orally bioavailable inhibitors that were selective for DDR1 and DDR2. The inhibitors were shown to potently inhibit DDR2 activity in cells but in contrast to unselective inhibitors such as dasatinib, they did not inhibit proliferation of mutant DDR2 lung SCC cell lines.

Fragment-Based Discovery of Potent and Selective DDR1/2 Inhibitors.,Murray CW, Berdini V, Buck IM, Carr ME, Cleasby A, Coyle JE, Curry JE, Day JE, Day PJ, Hearn K, Iqbal A, Lee LY, Martins V, Mortenson PN, Munck JM, Page LW, Patel S, Roomans S, Smith K, Tamanini E, Saxty G ACS Med Chem Lett. 2015 Jun 4;6(7):798-803. doi: 10.1021/acsmedchemlett.5b00143. , eCollection 2015 Jul 9. PMID:26191369<ref>PMID:26191369</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5bvw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Epithelial discoidin domain-containing receptor|Epithelial discoidin domain-containing receptor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Berdini V]]
[[Category: Buck I]]
[[Category: Carr M]]
[[Category: Cleasby A]]
[[Category: Coyle J]]
[[Category: Curry J]]
[[Category: Day J]]
[[Category: Hearn K]]
[[Category: Iqbal A]]
[[Category: Kirsten T]]
[[Category: Lee L]]
[[Category: Martins V]]
[[Category: Mortenson P]]
[[Category: Munck J]]
[[Category: Murray C]]
[[Category: Page L]]
[[Category: Patel S]]
[[Category: Roomans S]]
[[Category: Saxty G]]