6ENQ

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

Summary for 6ENQ

• Entry DOI: 10.2210/pdb6enq/pdb
• Descriptor: Peroxisome proliferator-activated receptor gamma, 4-[1-(1,3-benzothiazol-6-ylsulfonyl)-5-chloro-indol-2-yl]butanoic acid (3 entities in total)
• Functional Keywords: nuclear hormone receptor, ppargamma modulator, lanifibranor, transcription
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus: P37231
• Total number of polymer chains: 2
• Total formula weight: 64853.47

Authors

Boubia, B.,Poupardin, O.,Barth, M.,Amaudrut, J.,Broqua, P.,Tallandier, M.,Zeyer, D. (deposition date: 2017-10-06, release date: 2018-03-14, Last modification date: 2024-01-17)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.2 Å)