2gtk

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spinqualitylabelsall models PDB ID 2gtk Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 2.10Å
Ligands:
Gene:	PPARG, NR1C3 (Homo sapiens)
Coordinates:	save as pdb, mmCIF, xml

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[601487], Diabetes mellitus, insulin-resistant, with acanthosis nigricans and hypertension OMIM:[601487], Glioblastoma, susceptibility to OMIM:[601487], Insulin resistance, severe, digenic OMIM:[601487], Lipodystrophy, familial partial OMIM:[601487], Obesity, resistance to OMIM:[601487], Obesity, severe OMIM:[601487]

About this Structure

2GTK is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure-based design of indole propionic acids as novel PPARalpha/gamma co-agonists., Kuhn B, Hilpert H, Benz J, Binggeli A, Grether U, Humm R, Marki HP, Meyer M, Mohr P, Bioorg Med Chem Lett. 2006 Aug 1;16(15):4016-20. Epub 2006 Jun 5. PMID:16737814

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