6ENQ

Structure of human PPAR gamma LBD in complex with Lanifibranor (IVA337)

6ENQ の概要

• エントリーDOI: 10.2210/pdb6enq/pdb
• 分子名称: Peroxisome proliferator-activated receptor gamma, 4-[1-(1,3-benzothiazol-6-ylsulfonyl)-5-chloro-indol-2-yl]butanoic acid (3 entities in total)
• 機能のキーワード: nuclear hormone receptor, ppargamma modulator, lanifibranor, transcription
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus: P37231
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 64853.47

構造登録者

Boubia, B.,Poupardin, O.,Barth, M.,Amaudrut, J.,Broqua, P.,Tallandier, M.,Zeyer, D. (登録日: 2017-10-06, 公開日: 2018-03-14, 最終更新日: 2024-01-17)

主引用文献

Boubia, B.,Poupardin, O.,Barth, M.,Binet, J.,Peralba, P.,Mounier, L.,Jacquier, E.,Gauthier, E.,Lepais, V.,Chatar, M.,Ferry, S.,Thourigny, A.,Guillier, F.,Llacer, J.,Amaudrut, J.,Dodey, P.,Lacombe, O.,Masson, P.,Montalbetti, C.,Wettstein, G.,Luccarini, J.M.,Legendre, C.,Junien, J.L.,Broqua, P.
Design, Synthesis, and Evaluation of a Novel Series of Indole Sulfonamide Peroxisome Proliferator Activated Receptor (PPAR) alpha / gamma / delta Triple Activators: Discovery of Lanifibranor, a New Antifibrotic Clinical Candidate.
J. Med. Chem., 61:2246-2265, 2018

PubMed Abstract: Here, we describe the identification and synthesis of novel indole sulfonamide derivatives that activate the three peroxisome proliferator activated receptor (PPAR) isoforms. Starting with a PPARα activator, compound 4, identified during a high throughput screening (HTS) of our proprietary screening library, a systematic optimization led to the discovery of lanifibranor (IVA337) 5, a moderately potent and well balanced pan PPAR agonist with an excellent safety profile. In vitro and in vivo, compound 5 demonstrated strong activity in models that are relevant to nonalcoholic steatohepatitis (NASH) pathophysiology suggesting therapeutic potential for NASH patients.

PubMed: 29446942
DOI: 10.1021/acs.jmedchem.7b01285

実験手法

X-RAY DIFFRACTION (2.2 Å)