8aqn

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Current revision (11:53, 23 October 2024) (edit) (undo)
 
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==Crystal structure of PPARG and peptide with modulator 2==
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==Crystal structure of PPARG and NCOR2 with BAY-4931, an inverse agonist (compound 6c)==
<StructureSection load='8aqn' size='340' side='right'caption='[[8aqn]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
<StructureSection load='8aqn' size='340' side='right'caption='[[8aqn]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/PPARG_HUMAN PPARG_HUMAN] Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses.<ref>PMID:9065481</ref> <ref>PMID:16150867</ref> <ref>PMID:20829347</ref>
[https://www.uniprot.org/uniprot/PPARG_HUMAN PPARG_HUMAN] Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses.<ref>PMID:9065481</ref> <ref>PMID:16150867</ref> <ref>PMID:20829347</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The ligand-activated nuclear receptor peroxisome-proliferator-activated receptor-gamma (PPARG or PPARgamma) represents a potential target for a new generation of cancer therapeutics, especially in muscle-invasive luminal bladder cancer where PPARgamma is a critical lineage driver. Here we disclose the discovery of a series of chloro-nitro-arene covalent inverse-agonists of PPARgamma that exploit a benzoxazole core to improve interactions with corepressors NCOR1 and NCOR2. In vitro treatment of sensitive cell lines with these compounds results in the robust regulation of PPARgamma target genes and antiproliferative effects. Despite their imperfect physicochemical properties, the compounds showed modest pharmacodynamic target regulation in vivo. Improvements to the in vitro potency and efficacy of BAY-4931 and BAY-0069 compared to those of previously described PPARgamma inverse-agonists show that these compounds are novel tools for probing the in vitro biology of PPARgamma inverse-agonism.
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Discovery and Structure-Based Design of Potent Covalent PPARgamma Inverse-Agonists BAY-4931 and BAY-0069.,Orsi DL, Pook E, Brauer N, Friberg A, Lienau P, Lemke CT, Stellfeld T, Bruggemeier U, Putter V, Meyer H, Baco M, Tang S, Cherniack AD, Westlake L, Bender SA, Kocak M, Strathdee CA, Meyerson M, Eis K, Goldstein JT J Med Chem. 2022 Nov 10;65(21):14843-14863. doi: 10.1021/acs.jmedchem.2c01379. , Epub 2022 Oct 21. PMID:36270630<ref>PMID:36270630</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 8aqn" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==

Current revision

Crystal structure of PPARG and NCOR2 with BAY-4931, an inverse agonist (compound 6c)

PDB ID 8aqn

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