4fc0: Difference between revisions

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 == Structural highlights ==
 <table><tr><td colspan='2'>[[4fc0]] 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=4FC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FC0 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0T2:2-CHLORO-3-[(2-CYANOPROPAN-2-YL)OXY]-N-{5-[{2-[(CYCLOPROPYLCARBONYL)AMINO][1,3]THIAZOLO[5,4-B]PYRIDIN-5-YL}(METHYL)AMINO]-2-FLUOROPHENYL}BENZAMIDE'>0T2</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]] 2.95&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0T2:2-CHLORO-3-[(2-CYANOPROPAN-2-YL)OXY]-N-{5-[{2-[(CYCLOPROPYLCARBONYL)AMINO][1,3]THIAZOLO[5,4-B]PYRIDIN-5-YL}(METHYL)AMINO]-2-FLUOROPHENYL}BENZAMIDE'>0T2</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=4fc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fc0 OCA], [https://pdbe.org/4fc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fc0 RCSB], [https://www.ebi.ac.uk/pdbsum/4fc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fc0 ProSAT]</span></td></tr>
 </table>
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 == Function ==
 [https://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN] Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron.
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Our aim was to discover RAF/vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors that possess strong activity and sufficient oral absorption, and thus, we selected a 5-amino-linked thiazolo[5,4-d]pyrimidine derivative as the lead compound because of its potential kinase inhibitory activities and its desired solubility. The novel tertiary 1-cyano-1-methylethoxy substituent was designed to occupy the hydrophobic region of 'back pocket' of BRAF on the basis of the X-ray co-crystal structure data of BRAF. In addition, we found that N-methylation of the amine linker could control the twisted molecular conformation leading to improved solubility. These approaches produced N-methyl thiazolo[5,4-b]pyridine-5-amine derivative 5. To maximize the in vivo efficacy, we attempted salt formation of 5. Our result indicated that the besylate monohydrate salt form (5c) showed significant improvement of both solubility and oral absorption. Owing to the improved physicochemical properties, compound 5c demonstrated regressive antitumor efficacy in a HT-29 xenograft model.
-Design and synthesis of novel DFG-out RAF/vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors: 3. Evaluation of 5-amino-linked thiazolo[5,4-d]pyrimidine and thiazolo[5,4-b]pyridine derivatives.,Hirose M, Okaniwa M, Miyazaki T, Imada T, Ohashi T, Tanaka Y, Arita T, Yabuki M, Kawamoto T, Tsutsumi S, Sumita A, Takagi T, Sang BC, Yano J, Aertgeerts K, Yoshida S, Ishikawa T Bioorg Med Chem. 2012 Sep 15;20(18):5600-15. doi: 10.1016/j.bmc.2012.07.032. Epub, 2012 Jul 23. PMID:22883026<ref>PMID:22883026</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 4fc0" style="background-color:#fffaf0;"></div>
 ==See Also==