4ksq: Difference between revisions

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 == Structural highlights ==
 <table><tr><td colspan='2'>[[4ksq]] 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=4KSQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KSQ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1SW:N-{7-CYANO-6-[4-FLUORO-3-({[3-(TRIFLUOROMETHYL)PHENYL]CARBAMOYL}AMINO)PHENOXY]-1,3-BENZOTHIAZOL-2-YL}CYCLOPROPANECARBOXAMIDE'>1SW</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]] 3.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1SW:N-{7-CYANO-6-[4-FLUORO-3-({[3-(TRIFLUOROMETHYL)PHENYL]CARBAMOYL}AMINO)PHENOXY]-1,3-BENZOTHIAZOL-2-YL}CYCLOPROPANECARBOXAMIDE'>1SW</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=4ksq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ksq OCA], [https://pdbe.org/4ksq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ksq RCSB], [https://www.ebi.ac.uk/pdbsum/4ksq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ksq 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 ==
-With the aim of discovering a selective kinase inhibitor targeting pan-RAF kinase inhibition, we designed novel 1,3-benzothiazole derivatives based on our thiazolo[5,4-b]pyridine class RAF/VEGFR2 inhibitor 1 and developed a regioselective cyclization methodology for the C-7-substituted 1,3-benzothiazole scaffold utilizing meta-substituted anilines. Eventually, we selected 7-cyano derivative 8B (TAK-632) as a development candidate and confirmed its binding mode by cocrystal structure with BRAF. Accommodation of the 7-cyano group into the BRAF-selectivity pocket and the 3-(trifluoromethyl)phenyl acetamide moiety into the hydrophobic back pocket of BRAF in the DFG-out conformation contributed to enhanced RAF potency and selectivity vs VEGFR2. Reflecting its potent pan-RAF inhibition and slow off-rate profile, 8B demonstrated significant cellular activity against mutated BRAF or mutated NRAS cancer cell lines. Furthermore, in both A375 (BRAF(V600E)) and HMVII (NRAS(Q61K)) xenograft models in rats, 8B demonstrated regressive antitumor efficacy by twice daily, 14-day repetitive administration without significant body weight loss.
-Discovery of a Selective Kinase Inhibitor (TAK-632) Targeting Pan-RAF Inhibition: Design, Synthesis, and Biological Evaluation of C-7-Substituted 1,3-Benzothiazole Derivatives.,Okaniwa M, Hirose M, Arita T, Yabuki M, Nakamura A, Takagi T, Kawamoto T, Uchiyama N, Sumita A, Tsutsumi S, Tottori T, Inui Y, Sang BC, Yano J, Aertgeerts K, Yoshida S, Ishikawa T J Med Chem. 2013 Aug 22;56(16):6478-94. doi: 10.1021/jm400778d. Epub 2013 Aug 1. PMID:23906342<ref>PMID:23906342</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 4ksq" style="background-color:#fffaf0;"></div>
 ==See Also==