4MF3

Crystal Structure of Human GRIK1 complexed with a 6-(tetrazolyl)aryl decahydroisoquinoline antagonist

4MF3 の概要

• エントリーDOI: 10.2210/pdb4mf3/pdb
• 分子名称: Glutamate receptor ionotropic, kainate 1, (3S,4aS,6S,8aR)-6-[3-chloro-2-(1H-tetrazol-5-yl)phenoxy]decahydroisoquinoline-3-carboxylic acid (3 entities in total)
• 機能のキーワード: protein-ligand complex, ligand gated ion channel, glutamate receptor, glutamate binding, none, membrane, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane; Multi-pass membrane protein: P39086
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59973.57

構造登録者

Martinez-Perez, J.A.,Iyengar, S.,Shannon, H.E.,Bleakman, D.,Alt, A.,Clawson, D.K.,Arnold, B.M.,Bell, M.G.,Bleisch, T.J.,Castano, A.M.,Del Prado, M.,Dominguez, E.,Escribano, A.M.,Filla, S.A.,Ho, K.H.,Hudziak, K.J.,Jones, C.K.,Katofiasc, M.A.,Mateo, A.,Mathes, B.M.,Mattiuz, E.L.,Ogden, A.M.L.,Phebus, L.A.,Simmons, R.M.A.,Stack, D.R.,Stratford, R.E.,Winter, M.A.,Wu, Z.,Ornstein, P.L. (登録日: 2013-08-27, 公開日: 2014-05-07, 最終更新日: 2024-11-06)

主引用文献

Martinez-Perez, J.A.,Iyengar, S.,Shannon, H.E.,Bleakman, D.,Alt, A.,Clawson, D.K.,Arnold, B.M.,Bell, M.G.,Bleisch, T.J.,Castano, A.M.,Del Prado, M.,Dominguez, E.,Escribano, A.M.,Filla, S.A.,Ho, K.H.,Hudziak, K.J.,Jones, C.K.,Mateo, A.,Mathes, B.M.,Mattiuz, E.L.,Ogden, A.M.,Simmons, R.M.,Stack, D.R.,Stratford, R.E.,Winter, M.A.,Wu, Z.,Ornstein, P.L.
GluK1 antagonists from 6-(tetrazolyl)phenyl decahydroisoquinoline derivatives: in vitro profile and in vivo analgesic efficacy.
Bioorg.Med.Chem.Lett., 23:6463-6466, 2013

PubMed Abstract: We have explored the decahydroisoquinoline scaffold, bearing a phenyl tetrazole, as GluK1 antagonists with potential as oral analgesics. We have established the optimal linker atom between decahydroisoquinoline and phenyl rings and demonstrated an improvement of both the affinity for the GluK1 receptor and the selectivity against the related GluA2 receptor with proper phenyl substitution. In this Letter, we also disclose in vivo data that led to the discovery of LY545694·HCl, a compound with oral efficacy in two persistent pain models.

PubMed: 24140446
DOI: 10.1016/j.bmcl.2013.09.045

実験手法

X-RAY DIFFRACTION (3 Å)