2gtk
From Proteopedia
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Structure-based Design of Indole Propionic Acids as Novel PPARag CO-Agonists
Contents |
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 with 208 as ligand. 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
Page seeded by OCA on Mon Nov 12 22:22:34 2007
Categories: Homo sapiens | Protein complex | Benz, J. | Binggeli, A. | Grether, U. | Hilpert, H. | Humm, R. | Kuhn, B. | Maerki, H.P. | Meyer, M. | Mohr, P. | 208 | Nuclear receptor
