2gtk: Difference between revisions
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'''Structure-based Design of Indole Propionic Acids as Novel PPARag CO-Agonists'''<br /> | '''Structure-based Design of Indole Propionic Acids as Novel PPARag CO-Agonists'''<br /> | ||
==Overview== | ==Overview== | ||
In the quest for novel PPARalpha/gamma co-agonists as putative drugs for | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
2GTK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with 208 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 2GTK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=208:'>208</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GTK OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Humm, R.]] | [[Category: Humm, R.]] | ||
[[Category: Kuhn, B.]] | [[Category: Kuhn, B.]] | ||
[[Category: Maerki, H | [[Category: Maerki, H P.]] | ||
[[Category: Meyer, M.]] | [[Category: Meyer, M.]] | ||
[[Category: Mohr, P.]] | [[Category: Mohr, P.]] | ||
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[[Category: nuclear receptor]] | [[Category: nuclear receptor]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:35:11 2008'' | ||
Revision as of 15:35, 21 February 2008
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Structure-based Design of Indole Propionic Acids as Novel PPARag CO-Agonists
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
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