2gtk: Difference between revisions
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[[Image:2gtk.gif|left|200px]] | [[Image:2gtk.gif|left|200px]] | ||
'''Structure-based Design of Indole Propionic Acids as Novel PPARag CO-Agonists''' | {{Structure | ||
|PDB= 2gtk |SIZE=350|CAPTION= <scene name='initialview01'>2gtk</scene>, resolution 2.10Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=208:(2S)-3-(1-{[2-(2-CHLOROPHENYL)-5-METHYL-1,3-OXAZOL-4-YL]METHYL}-1H-INDOL-5-YL)-2-ETHOXYPROPANOIC ACID'>208</scene> | |||
|ACTIVITY= | |||
|GENE= PPARG, NR1C3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Structure-based Design of Indole Propionic Acids as Novel PPARag CO-Agonists''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2GTK is a [ | 2GTK is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GTK OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/16737814 16737814] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: nuclear receptor]] | [[Category: nuclear receptor]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:08:58 2008'' | ||
Revision as of 18:08, 20 March 2008
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| , resolution 2.10Å | |||||||
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| Ligands: | |||||||
| Gene: | PPARG, NR1C3 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure-based Design of Indole Propionic Acids as Novel PPARag CO-Agonists
OverviewOverview
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.
DiseaseDisease
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 StructureAbout this Structure
2GTK is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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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