6ILQ

Crystal structure of PPARgamma with compound BR101549

6ILQ の概要

• エントリーDOI: 10.2210/pdb6ilq/pdb
• 分子名称: Peroxisome proliferator-activated receptor gamma, Nuclear receptor coactivator 1, ethyl [2-butyl-6-oxo-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]methyl}-4-(propan-2-yl)-1,6-dihydropyrimidin-5-yl]acetate, ... (4 entities in total)
• 機能のキーワード: peroxisome proliferator-activated receptor-g(ppar-g), transcription factor, ligand-binding domain, steroid receptor coactivator-1, nuclear protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34430.91

構造登録者

Hong, E.,Jang, T.H.,Chin, J.,Kim, K.H.,Jung, W.,Kim, S.H. (登録日: 2018-10-19, 公開日: 2019-09-11, 最終更新日: 2023-11-22)

主引用文献

Choung, W.,Jung, H.J.,Yang, D.,Nam, E.H.,Choi, H.,Lee, B.R.,Park, M.,Jang, S.M.,Lim, J.S.,Kim, W.S.,Kim, K.H.,Chin, J.,Jung, K.,Lee, G.,Hong, E.,Jang, T.H.,Myung, J.,Kim, S.H.
Identification of BR101549 as a lead candidate of non-TZD PPAR gamma agonist for the treatment of type 2 diabetes: Proof-of-concept evaluation and SAR.
Bioorg.Med.Chem.Lett., 29:631-637, 2019

PubMed Abstract: The new class of PPARgamma non-TZD agonist originally derived from the backbone of anti-hypertensive Fimasartan, BR101549, was identified as a potential lead for anti-diabetic drug development. The X-ray crystallography of BR101549 with PPARgamma ligand binding domain (LBD) revealed unique binding characteristics versus traditional TZD full agonists. The lead candidate, BR101549, has been found activating PPARgamma to the level of Pioglitazone in vitro and indeed has demonstrated its effects on blood glucose control in mouse proof-of-concept evaluation. The attempts to improve its metabolic stability profile through follow-up SAR including deuterium incorporation have been also described.

PubMed: 30594432
DOI: 10.1016/j.bmcl.2018.12.043

実験手法

X-RAY DIFFRACTION (2.408 Å)