2gtk
From Proteopedia
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|PDB= 2gtk |SIZE=350|CAPTION= <scene name='initialview01'>2gtk</scene>, resolution 2.10Å | |PDB= 2gtk |SIZE=350|CAPTION= <scene name='initialview01'>2gtk</scene>, resolution 2.10Å | ||
|SITE= | |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> | + | |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= | |ACTIVITY= | ||
|GENE= PPARG, NR1C3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= PPARG, NR1C3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gtk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gtk OCA], [http://www.ebi.ac.uk/pdbsum/2gtk PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2gtk RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601487 601487]], Diabetes mellitus, insulin-resistant, with acanthosis nigricans and hypertension OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601487 601487]], Glioblastoma, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601487 601487]], Insulin resistance, severe, digenic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601487 601487]], Lipodystrophy, familial partial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601487 601487]], Obesity, resistance to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601487 601487]], Obesity, severe OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601487 601487]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Meyer, M.]] | [[Category: Meyer, M.]] | ||
[[Category: Mohr, P.]] | [[Category: Mohr, P.]] | ||
| - | [[Category: 208]] | ||
[[Category: nuclear receptor]] | [[Category: nuclear receptor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:21:24 2008'' |
Revision as of 00:21, 31 March 2008
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| , resolution 2.10Å | |||||||
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| Ligands: | |||||||
| Gene: | PPARG, NR1C3 (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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.
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
Page seeded by OCA on Mon Mar 31 03:21:24 2008
Categories: Homo sapiens | Protein complex | Benz, J. | Binggeli, A. | Grether, U. | Hilpert, H. | Humm, R. | Kuhn, B. | Maerki, H P. | Meyer, M. | Mohr, P. | Nuclear receptor
