5JY3

CRYSTAL STRUCTURE OF LXRbeta (NUCLEAR RECEPTOR SUBFAMILY 1, GROUP H, MEMBER 2) COMPLEXED WITH BMS-852927

5JY3 の概要

• エントリーDOI: 10.2210/pdb5jy3/pdb
• 分子名称: Oxysterols receptor LXR-beta, 2-[2-[2-[2,6-bis(chloranyl)phenyl]propan-2-yl]-1-[2-fluoranyl-4-[3-fluoranyl-4-(hydroxymethyl)-5-methylsulfonyl-phenyl] phenyl]imidazol-4-yl]propan-2-ol, 1,4-BUTANEDIOL, ... (4 entities in total)
• 機能のキーワード: nhr, nr1h2, lxr-b, lxrb, unr, ner-i, rip15, ner, transcription
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus : P55055
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 124789.70

構造登録者

Muckelbauer, J.K. (登録日: 2016-05-13, 公開日: 2016-11-02, 最終更新日: 2024-03-06)

主引用文献

Kick, E.K.,Busch, B.B.,Martin, R.,Stevens, W.C.,Bollu, V.,Xie, Y.,Boren, B.C.,Nyman, M.C.,Nanao, M.H.,Nguyen, L.,Plonowski, A.,Schulman, I.G.,Yan, G.,Zhang, H.,Hou, X.,Valente, M.N.,Narayanan, R.,Behnia, K.,Rodrigues, A.D.,Brock, B.,Smalley, J.,Cantor, G.H.,Lupisella, J.,Sleph, P.,Grimm, D.,Ostrowski, J.,Wexler, R.R.,Kirchgessner, T.,Mohan, R.
Discovery of Highly Potent Liver X Receptor beta Agonists.
ACS Med Chem Lett, 7:1207-1212, 2016

PubMed Abstract: Introducing a uniquely substituted phenyl sulfone into a series of biphenyl imidazole liver X receptor (LXR) agonists afforded a dramatic potency improvement for induction of ATP binding cassette transporters, ABCA1 and ABCG1, in human whole blood. The agonist series demonstrated robust LXRβ activity (>70%) with low partial LXRα agonist activity (<25%) in cell assays, providing a window between desired blood cell ABCG1 gene induction in cynomolgus monkeys and modest elevation of plasma triglycerides for agonist . The addition of polarity to the phenyl sulfone also reduced binding to the plasma protein, human α-1-acid glycoprotein. Agonist was selected for clinical development based on the favorable combination of properties, excellent pharmacokinetic parameters, and a favorable lipid profile.

PubMed: 27994765
DOI: 10.1021/acsmedchemlett.6b00234

実験手法

X-RAY DIFFRACTION (2.4 Å)