2GTK

Structure-based Design of Indole Propionic Acids as Novel PPARag CO-Agonists

Summary for 2GTK

• Entry DOI: 10.2210/pdb2gtk/pdb
• Descriptor: Peroxisome proliferator-activated receptor gamma, Decamer from Nuclear receptor coactivator 1, (2S)-3-(1-{[2-(2-CHLOROPHENYL)-5-METHYL-1,3-OXAZOL-4-YL]METHYL}-1H-INDOL-5-YL)-2-ETHOXYPROPANOIC ACID, ... (4 entities in total)
• Functional Keywords: nuclear receptor, transcription regulator
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P37231 Q15788
• Total number of polymer chains: 2
• Total formula weight: 32591.31

Authors

Kuhn, B.,Hilpert, H.,Benz, J.,Binggeli, A.,Grether, U.,Humm, R.,Maerki, H.-P.,Meyer, M.,Mohr, P. (deposition date: 2006-04-28, release date: 2006-09-26, Last modification date: 2024-04-03)

Primary citation

Kuhn, B.,Hilpert, H.,Benz, J.,Binggeli, A.,Grether, U.,Humm, R.,Meyer, M.,Mohr, P.
Structure-based design of indole propionic acids as novel PPARalpha/gamma co-agonists
Bioorg.Med.Chem.Lett., 16:4016-4020, 2006

PubMed Abstract: In the quest for novel PPARalpha/gamma co-agonists as putative drugs for the treatment of type 2 diabetes and dyslipidemia, we have used a structure-based design approach to identify propionic acids with a 1,5-disubstituted indole scaffold as potent PPARalpha/gamma activators. Compounds 13, 24, and 28 are examples of submicromolar dual agonists with different alpha/gamma EC50 ratios that are selective against the delta-isoform. Analysis of the X-ray complex structure of PPARgamma with the indole propionic acid 13 provides a rationalization for some of the observed SAR.

PubMed: 16737814
DOI: 10.1016/j.bmcl.2006.05.007

Experimental method

X-RAY DIFFRACTION (2.1 Å)