5CGD

Structure of the human class C GPCR metabotropic glutamate receptor 5 transmembrane domain in complex with the negative allosteric modulator 3-chloro-5-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]benzonitrile - (HTL14242)

5CGD の概要

• エントリーDOI: 10.2210/pdb5cgd/pdb
• 関連するPDBエントリー: 4OO9 5CGC
• 分子名称: Metabotropic glutamate receptor 5,Endolysin,Metabotropic glutamate receptor 5, OLEIC ACID, 3-chloro-5-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]benzonitrile, ... (4 entities in total)
• 機能のキーワード: 7tm, receptor, gpcr, membrane-protein, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 51243.09

構造登録者

Christopher, J.A.,Aves, S.J.,Bennett, K.A.,Dore, A.S.,Errey, J.C.,Jazayeri, A.,Marshall, F.H.,Okrasa, K.,Serrano-Vega, M.J.,Tehan, B.G.,Wiggin, G.R.,Congreve, M. (登録日: 2015-07-09, 公開日: 2015-08-12, 最終更新日: 2024-11-20)

主引用文献

Christopher, J.A.,Aves, S.J.,Bennett, K.A.,Dore, A.S.,Errey, J.C.,Jazayeri, A.,Marshall, F.H.,Okrasa, K.,Serrano-Vega, M.J.,Tehan, B.G.,Wiggin, G.R.,Congreve, M.
Fragment and Structure-Based Drug Discovery for a Class C GPCR: Discovery of the mGlu5 Negative Allosteric Modulator HTL14242 (3-Chloro-5-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]benzonitrile).
J.Med.Chem., 58:6653-6664, 2015

PubMed Abstract: Fragment screening of a thermostabilized mGlu5 receptor using a high-concentration radioligand binding assay enabled the identification of moderate affinity, high ligand efficiency (LE) pyrimidine hit 5. Subsequent optimization using structure-based drug discovery methods led to the selection of 25, HTL14242, as an advanced lead compound for further development. Structures of the stabilized mGlu5 receptor complexed with 25 and another molecule in the series, 14, were determined at resolutions of 2.6 and 3.1 Å, respectively.

PubMed: 26225459
DOI: 10.1021/acs.jmedchem.5b00892

実験手法

X-RAY DIFFRACTION (2.603 Å)