6ILQ

Crystal structure of PPARgamma with compound BR101549

Summary for 6ILQ

• Entry DOI: 10.2210/pdb6ilq/pdb
• Descriptor: 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)
• Functional Keywords: peroxisome proliferator-activated receptor-g(ppar-g), transcription factor, ligand-binding domain, steroid receptor coactivator-1, nuclear protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 34430.91

Authors

Hong, E.,Jang, T.H.,Chin, J.,Kim, K.H.,Jung, W.,Kim, S.H. (deposition date: 2018-10-19, release date: 2019-09-11, Last modification date: 2023-11-22)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.408 Å)