Structure of the PPARalpha and -gamma ligand binding domain in complex with AZ 242; ligand selectivity and agonist activation in the PPAR family.
paper
Cited
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- Authors
- Cronet, P; Petersen, J F; Folmer, R; Blomberg, N; SjΓΆblom, K; Karlsson, U; Lindstedt, E L; Bamberg, K
- Year
- 2001
- Journal
- Structure (London, England : 1993)
- PMID
- 11587644
- DOI
- 10.1016/s0969-2126(01)00634-7
BACKGROUND: The peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors belonging to the nuclear receptor family. The roles of PPARalpha in fatty acid oxidation and PPARgamma in adipocyte differentiation and lipid storage have been characterized extensively. PPARs are activated by fatty acids and eicosanoids and are also targets for antidyslipidemic drugs, but the molecular interactions governing ligand selectivity for specific subtypes are unclear due to the lack of a PPARalpha ligand binding domain structure. RESULTS: We have solved the crystal structure of the PPARalpha ligand binding domain (LBD) in complex with the combined PPARalpha and -gamma agonist AZ 242, a novel dihydro cinnamate derivative that is structurally different from thiazolidinediones. In addition, we present the crystal structure of the PPARgamma_LBD/AZ 242 complex and provide a rationale for ligand selectivity toward the PPARalpha and -gamma subtypes. Heteronuclear NMR data on PPARalpha in both the apo form and in complex with AZ 242 shows an overall stabilization of the LBD upon agonist binding. A comparison of the novel PPARalpha/AZ 242 complex with the PPARgamma/AZ 242 complex and previously solved PPARgamma structures reveals a conserved hydrogen bonding network between agonists and the AF2 helix. CONCLUSIONS: The complex of PPARalpha and PPARgamma with the dual specificity agonist AZ 242 highlights the conserved interactions required for receptor activation. Together with the NMR data, this suggests a general model for ligand activation in the PPAR family. A comparison of the ligand binding sites reveals a molecular explanation for subtype selectivity and provides a basis for rational drug design.
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| PPARΞ± and NCOR/SMRT corepressor network in liver metabolic regulation. | Kang Z et al. | β | 2020 | β |
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| Discovery of a Novel Selective Dual Peroxisome Proliferator-Activated Receptor Ξ±/Ξ΄ Agonist for the Treatment of Primary Biliary Cirrhosis. | Jiang Z et al. | β | 2019 | β |
| Effects of Dual Peroxisome Proliferator-Activated Receptors <i>Ξ±</i> and <i>Ξ³</i> Activation in Two Rat Models of Neuropathic Pain. | Alsalem M et al. | β | 2019 | β |
| Identification of novel PPARΞ±/Ξ³ dual agonists by pharmacophore screening, docking analysis, ADMET prediction and molecular dynamics simulations. | Feng XY et al. | β | 2019 | β |
| Multi-Target Drugs Against Metabolic Disorders. | Scotti L et al. | β | 2019 | β |
| Rosiglitazone-dependent dissociation of HuR from PPAR-Ξ³ regulates adiponectin expression at the posttranscriptional level. | Hwang JS et al. | β | 2019 | β |
| The effects of short-chain fatty acids on the transcription and secretion of apolipoprotein A-I in human hepatocytes in vitro. | Tayyeb JZ et al. | β | 2019 | β |
| Alterbrassicicene A, a Highly Transformed Fusicoccane-Derived Diterpenoid with Potent PPAR-Ξ³ Agonistic Activity from Alternaria brassicicola. | Li F et al. | β | 2018 | β |
| Deciphering PPARΞ³ activation in cardiometabolic syndrome: studies by in silico and in vivo experimental assessment. | Agrawal R et al. | β | 2018 | β |
| Design, synthesis, and evaluation of novel l-phenylglycine derivatives as potential PPARΞ³ lead compounds. | Liu J et al. | β | 2018 | β |
| Identification of novel PPARΞ±/Ξ³ dual agonists by virtual screening, ADMET prediction and molecular dynamics simulations. | Liu X et al. | β | 2018 | β |
| Molecular Actions of PPARΞ± in Lipid Metabolism and Inflammation. | Bougarne N et al. | β | 2018 | β |
| Norbixin, an apocarotenoid derivative activates PPARΞ³ in cardiometabolic syndrome: Validation by in silico and in vivo experimental assessment. | A R et al. | β | 2018 | β |
| Plasticizers used in food-contact materials affect adipogenesis in 3T3-L1 cells. | Pomatto V et al. | β | 2018 | β |
| The Opportunities and Challenges of Peroxisome Proliferator-Activated Receptors Ligands in Clinical Drug Discovery and Development. | Hong F et al. | β | 2018 | β |
| Virtual identification of novel PPARΞ±/Ξ³ dual agonists by scaffold hopping of saroglitazar. | Jia WQ et al. | β | 2018 | β |
| A Molecular Dynamics-Shared Pharmacophore Approach to Boost Early-Enrichment Virtual Screening: A Case Study on Peroxisome Proliferator-Activated Receptorβ Ξ±. | Perricone U et al. | β | 2017 | β |
| Arjunolic acid, a peroxisome proliferator-activated receptor Ξ± agonist, regresses cardiac fibrosis by inhibiting non-canonical TGF-Ξ² signaling. | Bansal T et al. | β | 2017 | β |
| Design, sythesis and evaluation of a series of 3- or 4-alkoxy substituted phenoxy derivatives as PPARs agonists. | Zhang J et al. | β | 2017 | β |
| Di-(2-ethylhexyl) phthalate could disrupt the insulin signaling pathway in liver of SD rats and L02 cells via PPARΞ³. | Zhang W et al. | β | 2017 | β |
| Genomic Activation of <i>PPARG</i> Reveals a Candidate Therapeutic Axis in Bladder Cancer. | Goldstein JT et al. | β | 2017 | β |
| In silico design, chemical synthesis and toxicological evaluation of 1,3-thiazolidine-2,4-dione derivatives as PPARΞ³ agonists. | AlemΓ‘n-GonzΓ‘lez-Duhart D et al. | β | 2017 | β |
| New diphenylmethane derivatives as peroxisome proliferator-activated receptor alpha/gamma dual agonists endowed with anti-proliferative effects and mitochondrial activity. | Piemontese L et al. | β | 2017 | β |
| Peroxisome proliferator-activated receptor Ξ± ligands and modulators from dietary compounds: Types, screening methods and functions. | Yang H et al. | β | 2017 | β |
| Study of new interactions of glitazone's stereoisomers and the endogenous ligand 15d-PGJ2 on six different PPAR gamma proteins. | Γlvarez-AlmazΓ‘n S et al. | β | 2017 | β |
| The application of molecular modelling in the safety assessment of chemicals: A case study on ligand-dependent PPARΞ³ dysregulation. | Al Sharif M et al. | β | 2017 | β |
| 17-OxoDHA Is a PPARΞ±/Ξ³ Dual Covalent Modifier and Agonist. | Egawa D et al. | β | 2016 | β |
| Design and synthesis of novel Y-shaped barbituric acid derivatives as PPARΞ³ activators. | Dixit VA et al. | β | 2016 | β |
| Docking study: PPARs interaction with the selected alternative plasticizers to di(2-ethylhexyl) phthalate. | Kambia N et al. | β | 2016 | β |
| Monitoring Solution Structures of Peroxisome Proliferator-Activated Receptor Ξ²/Ξ΄ upon Ligand Binding. | Schwarz R et al. | β | 2016 | β |
| Structures and regulation of non-X orphan nuclear receptors: A retinoid hypothesis. | Zhi X et al. | β | 2016 | β |
| The conformational dynamics of H2-H3n and S2-H6 in gating ligand entry into the buried binding cavity of vitamin D receptor. | Tee WV et al. | β | 2016 | β |
| Tri-<i>m</i>-cresyl phosphate and PPAR/LXR interactions in seabream hepatocytes: revealed by computational modeling (docking) and transcriptional regulation of signaling pathways. | Palermo FA et al. | β | 2016 | β |
| Activation helix orientation of the estrogen receptor is mediated by receptor dimerization: evidence from molecular dynamics simulations. | Fratev F | β | 2015 | β |
| Activation of PPARΞ΄: from computer modelling to biological effects. | Kahremany S et al. | β | 2015 | β |
| Different binding and recognition modes of GL479, a dual agonist of Peroxisome Proliferator-Activated Receptor Ξ±/Ξ³. | dos Santos JC et al. | β | 2015 | β |
| Molecular mechanism of PPARΞ± action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. | Pawlak M et al. | β | 2015 | β |
| Overview of clinically approved oral antidiabetic agents for the treatment of type 2 diabetes mellitus. | He ZX et al. | β | 2015 | β |
| Peroxisome proliferator-activated receptors Ξ± and Ξ³ are linked with alcohol consumption in mice and withdrawal and dependence in humans. | Blednov YA et al. | β | 2015 | β |
| Differential effects of triclosan on the activation of mouse and human peroxisome proliferator-activated receptor alpha. | Wu Y et al. | β | 2014 | β |
| Fatty acid chain length and saturation influences PPARΞ± transcriptional activation and repression in HepG2 cells. | Popeijus HE et al. | β | 2014 | β |
| Identification of novel multitargeted PPARΞ±/Ξ³/Ξ΄ pan agonists by core hopping of rosiglitazone. | Wang XJ et al. | β | 2014 | β |
| Molecular determinants for improved activity at PPARΞ±: structure-activity relationship of pirinixic acid derivatives, docking study and site-directed mutagenesis of PPARΞ±. | Lamers C et al. | β | 2014 | β |
| Molecular modelling study of the PPARΞ³ receptor in relation to the mode of action/adverse outcome pathway framework for liver steatosis. | Tsakovska I et al. | β | 2014 | β |
| Molecular recognition of agonist and antagonist for peroxisome proliferator-activated receptor-Ξ± studied by molecular dynamics simulations. | Liu M et al. | β | 2014 | β |
| Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor Ξ±, Ξ², Ξ³ subtypes: an in silico approach. | Sarath Josh MK et al. | β | 2014 | β |
| Structure-dependent binding and activation of perfluorinated compounds on human peroxisome proliferator-activated receptor Ξ³. | Zhang L et al. | β | 2014 | β |
| Analysis of PPAR-Ξ±/Ξ³ Activity by Combining 2-D QSAR and Molecular Simulation. | Vallianatou T et al. | β | 2013 | β |
| Combined biophysical and cell-based approaches for the assessment of ligand binding to PPARΞ³. | Zorrilla S et al. | β | 2013 | β |
| Designing drugs with multi-target activity: the next step in the treatment of neurodegenerative disorders. | Geldenhuys WJ et al. | β | 2013 | β |
| Discovery of INT131: a selective PPARΞ³ modulator that enhances insulin sensitivity. | Taygerly JP et al. | β | 2013 | β |
| Interactions between Human Liver Fatty Acid Binding Protein and Peroxisome Proliferator Activated Receptor Selective Drugs. | Velkov T | β | 2013 | β |
| Molecular docking of Glyceroneogenesis pathway intermediates with Peroxisome Proliferator- Activated Receptor-Alpha (PPAR-Ξ±). | Subramani PA et al. | β | 2013 | β |
| Molecular mechanism of peroxisome proliferator-activated receptor Ξ± activation by WY14643: a new mode of ligand recognition and receptor stabilization. | Bernardes A et al. | β | 2013 | β |
| Monitoring conformational changes in peroxisome proliferator-activated receptor Ξ± by a genetically encoded photoamino acid, cross-linking, and mass spectrometry. | Schwarz R et al. | β | 2013 | β |
| Nuclear receptors and their selective pharmacologic modulators. | Burris TP et al. | β | 2013 | β |
| Scutellarin from Scutellaria baicalensis suppresses adipogenesis by upregulating PPARΞ± in 3T3-L1 cells. | Lu K et al. | β | 2013 | β |
| Small molecule modulation of nuclear receptor conformational dynamics: implications for function and drug discovery. | Kojetin DJ et al. | β | 2013 | β |
| Structural characterization of amorfrutins bound to the peroxisome proliferator-activated receptor Ξ³. | de Groot JC et al. | β | 2013 | β |
| Structure-based investigation on the interaction of perfluorinated compounds with human liver fatty acid binding protein. | Zhang L et al. | β | 2013 | β |
| Synthesis and evaluation of 2,3-dinorprostaglandins: Dinor-PGD1 and 13-epi-dinor-PGD1 are peroxisome proliferator-activated receptor Ξ±/Ξ³ dual agonists. | Sato A et al. | β | 2013 | β |
| The PPAR Ξ± / Ξ³ Agonist, Tesaglitazar, Improves Insulin Mediated Switching of Tissue Glucose and Free Fatty Acid Utilization In Vivo in the Obese Zucker Rat. | Wallenius K et al. | β | 2013 | β |
| Transient expression, purification and characterisation of human full-length PPARΞ³2 in HEK293 cells. | Liu J et al. | β | 2013 | β |
| Amorfrutins are potent antidiabetic dietary natural products. | Weidner C et al. | β | 2012 | β |
| A new class of non-thiazolidinedione, non-carboxylic-acid-based highly selective peroxisome proliferator-activated receptor (PPAR) Ξ³ agonists: design and synthesis of benzylpyrazole acylsulfonamides. | Rikimaru K et al. | β | 2012 | β |
| Design and synthesis of marine fungal phthalide derivatives as PPAR-Ξ³ agonists. | Xiao B et al. | β | 2012 | β |
| Design novel dual agonists for treating type-2 diabetes by targeting peroxisome proliferator-activated receptors with core hopping approach. | Ma Y et al. | β | 2012 | β |
| Design, synthesis and evaluation of novel zwitterionic compounds as PPARΞ±/Ξ³ dual agonists (1). | Shibata Y et al. | β | 2012 | β |
| Fibrate-derived N-(methylsulfonyl)amides with antagonistic properties on PPARΞ±. | Ammazzalorso A et al. | β | 2012 | β |
| Novel (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids: peroxisome proliferator-activated receptor Ξ³ selective agonists with protein-tyrosine phosphatase 1B inhibition. | Otake K et al. | β | 2012 | β |
| Peroxisome proliferator-activated receptors (PPARs) have multiple binding points that accommodate ligands in various conformations: phenylpropanoic acid-type PPAR ligands bind to PPAR in different conformations, depending on the subtype. | Kuwabara N et al. | β | 2012 | β |
| Regulation of GPR119 receptor activity with endocannabinoid-like lipids. | Syed SK et al. | β | 2012 | β |
| Scaffold-based pan-agonist design for the PPARΞ±, PPARΞ² and PPARΞ³ receptors. | Zhang LS et al. | β | 2012 | β |
| Structure and activation of rhodopsin. | Zhou XE et al. | β | 2012 | β |
| Tesaglitazar, a dual PPAR-Ξ±/Ξ³ agonist, hamster carcinogenicity, investigative animal and clinical studies. | Lindblom P et al. | β | 2012 | β |
| A novel series of (S)-2,7-substituted-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids: peroxisome proliferator-activated receptor Ξ±/Ξ³ dual agonists with protein-tyrosine phosphatase 1B inhibitory activity. | Otake K et al. | β | 2011 | β |
| Prediction of the PPARΞ± agonism of fibrates by combined MM-docking approaches. | Lannutti F et al. | β | 2011 | β |
| Simple defined autoinduction medium for high-level recombinant protein production using T7-based Escherichia coli expression systems. | Li Z et al. | β | 2011 | β |
| Structural dynamics, intrinsic disorder, and allostery in nuclear receptors as transcription factors. | Hilser VJ et al. | β | 2011 | β |
| Synthesis and pharmacological evaluation of novel benzoylazole-based PPAR Ξ±/Ξ³ activators. | Ushiroda K et al. | β | 2011 | β |
| Acyl glucuronides: the good, the bad and the ugly. | Regan SL et al. | β | 2010 | β |
| Characterization of new PPARgamma agonists: benzimidazole derivatives-importance of positions 5 and 6, and computational studies on the binding mode. | Goebel M et al. | β | 2010 | β |
| Dynamic correlation networks in human peroxisome proliferator-activated receptor-Ξ³ nuclear receptor protein. | Fidelak J et al. | β | 2010 | β |
| Leukotriene B4 is a physiologically relevant endogenous peroxisome proliferator-activated receptor-alpha agonist. | Narala VR et al. | β | 2010 | β |
| Ligand-enhanced expression and in-cell assay of human peroxisome proliferator-activated receptor alpha ligand binding domain. | Velkov T et al. | β | 2010 | β |
| Peroxisome proliferator-activated receptor alpha target genes. | Rakhshandehroo M et al. | β | 2010 | β |
| PPARalpha: energy combustion, hypolipidemia, inflammation and cancer. | Pyper SR et al. | β | 2010 | β |
| Selective binding of the fluorescent dye 1-anilinonaphthalene-8-sulfonic acid to peroxisome proliferator-activated receptor gamma allows ligand identification and characterization. | Zorrilla S et al. | β | 2010 | β |
| The nuclear receptor PPARΞ³ individually responds to serotonin- and fatty acid-metabolites. | Waku T et al. | β | 2010 | β |
| Virtual Screening as a Technique for PPAR Modulator Discovery. | Lewis SN et al. | β | 2010 | β |
| Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures. | Oyama T et al. | β | 2009 | β |
| An innovative method to study target protein-drug interactions by mass spectrometry. | MΓΌller MQ et al. | β | 2009 | β |
| Design and biological evaluation of novel, balanced dual PPARalpha/gamma agonists. | Grether U et al. | β | 2009 | β |
| INT131: a selective modulator of PPAR gamma. | Motani A et al. | β | 2009 | β |
| Regulation of skeletal muscle physiology and metabolism by peroxisome proliferator-activated receptor delta. | Ehrenborg E et al. | β | 2009 | β |
| Selective, potent PPARgamma agonists with cyclopentenone core structure. | Otero MP et al. | β | 2009 | β |
| Soluble epoxide inhibition is protective against cerebral ischemia via vascular and neural protection. | Simpkins AN et al. | β | 2009 | β |
| Structure-based pharmacophore screening for natural-product-derived PPARgamma agonists. | Tanrikulu Y et al. | β | 2009 | β |
| Synthesis and evaluation of novel alpha-heteroaryl-phenylpropanoic acid derivatives as PPARalpha/gamma dual agonists. | Casimiro-Garcia A et al. | β | 2009 | β |
| The effect of antagonists on the conformational exchange of the retinoid X receptor alpha ligand-binding domain. | Lu J et al. | β | 2009 | β |
| A protocol for the combined sub-fractionation and delipidation of lipid binding proteins using hydrophobic interaction chromatography. | Velkov T et al. | β | 2008 | β |
| Are fish oil omega-3 long-chain fatty acids and their derivatives peroxisome proliferator-activated receptor agonists? | Gani OA | β | 2008 | β |
| Caenorhabditis elegans nuclear receptors: insights into life traits. | Magner DB et al. | β | 2008 | β |
| Effect of heterodimer partner RXRalpha on PPARgamma activation function-2 helix in solution. | Lu J et al. | β | 2008 | β |
| Effects of modifications of the linker in a series of phenylpropanoic acid derivatives: Synthesis, evaluation as PPARalpha/gamma dual agonists, and X-ray crystallographic studies. | Casimiro-Garcia A et al. | β | 2008 | β |
| Expression and purification of the ligand-binding domain of peroxisome proliferator-activated receptor alpha (PPARalpha). | MΓΌller MQ et al. | β | 2008 | β |
| Glucose directly links to lipid metabolism through high affinity interaction with peroxisome proliferator-activated receptor alpha. | Hostetler HA et al. | β | 2008 | β |
| Interference of pollutants with PPARs: endocrine disruption meets metabolism. | Casals-Casas C et al. | β | 2008 | β |
| Ligand-escape pathways from the ligand-binding domain of PPARgamma receptor as probed by molecular dynamics simulations. | Genest D et al. | β | 2008 | β |
| Ligand-induced stabilization and activation of peroxisome proliferator-activated receptor gamma. | Gani OA et al. | β | 2008 | β |
| Molecular mechanics and molecular orbital simulations on specific interactions between peroxisome proliferator-activated receptor PPARalpha and plasticizer. | Nakagawa T et al. | β | 2008 | β |
| Molecular modelling of phthalates - PPARs interactions. | Kambia N et al. | β | 2008 | β |
| Molecular recognition of docosahexaenoic acid by peroxisome proliferator-activated receptors and retinoid-X receptor alpha. | Gani OA et al. | β | 2008 | β |
| Peroxisome proliferator activated receptor gamma and oxidized docosahexaenoic acids as new class of ligand. | Itoh T et al. | β | 2008 | β |
| Peroxisome proliferator-activated receptors and the metabolic syndrome. | Bragt MC et al. | β | 2008 | β |
| Structural basis for the activation of PPARgamma by oxidized fatty acids. | Itoh T et al. | β | 2008 | β |
| The treatment of dyslipidemia--what's left in the pipeline? | Rau O et al. | β | 2008 | β |
| Ajulemic acid, a synthetic nonpsychoactive cannabinoid acid, bound to the ligand binding domain of the human peroxisome proliferator-activated receptor gamma. | Ambrosio ALB et al. | β | 2007 | β |
| Combined simulation and mutagenesis analyses reveal the involvement of key residues for peroxisome proliferator-activated receptor alpha helix 12 dynamic behavior. | Michalik L et al. | β | 2007 | β |
| Design and synthesis of 6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid derivatives as PPARgamma activators. | Kumar R et al. | β | 2007 | β |
| Design and synthesis of highly potent and selective human peroxisome proliferator-activated receptor alpha agonists. | Yamazaki Y et al. | β | 2007 | β |
| Design and synthesis of oxime ethers of alpha-acyl-beta-phenylpropanoic acids as PPAR dual agonists. | Oon Han H et al. | β | 2007 | β |
| Discovery of ligands for Nurr1 by combined use of NMR screening with different isotopic and spin-labeling strategies. | Poppe L et al. | β | 2007 | β |
| Insights into the mechanism of partial agonism: crystal structures of the peroxisome proliferator-activated receptor gamma ligand-binding domain in the complex with two enantiomeric ligands. | Pochetti G et al. | β | 2007 | β |
| Partial agonists activate PPARgamma using a helix 12 independent mechanism. | Bruning JB et al. | β | 2007 | β |
| Peroxisome proliferator-activated receptor gamma agonist action of 3-methyl-1,2-cyclopentanedione. | Choi SY et al. | β | 2007 | β |
| Quinoline-based derivatives of pirinixic acid as dual PPAR alpha/gamma agonists. | Popescu L et al. | β | 2007 | β |
| Substituted 2-[(4-aminomethyl)phenoxy]-2-methylpropionic acid PPARalpha agonists. 1. Discovery of a novel series of potent HDLc raising agents. | Sierra ML et al. | β | 2007 | β |
| Sulfonylureas and glinides exhibit peroxisome proliferator-activated receptor gamma activity: a combined virtual screening and biological assay approach. | Scarsi M et al. | β | 2007 | β |
| Synthesis, biological evaluation, and molecular modeling investigation of chiral phenoxyacetic acid analogues with PPARalpha and PPARgamma agonist activity. | Fracchiolla G et al. | β | 2007 | β |
| Tesaglitazar, a PPARalpha/gamma agonist, induces interstitial mesenchymal cell DNA synthesis and fibrosarcomas in subcutaneous tissues in rats. | Hellmold H et al. | β | 2007 | β |
| The endocrine disruptor monoethyl-hexyl-phthalate is a selective peroxisome proliferator-activated receptor gamma modulator that promotes adipogenesis. | Feige JN et al. | β | 2007 | β |
| 1,3,5-Trisubstituted aryls as highly selective PPARdelta agonists. | Epple R et al. | β | 2006 | β |
| Design, synthesis, and evaluation of 2-alkoxydihydrocinnamates as PPAR agonists. | Lu Y et al. | β | 2006 | β |
| Food does not affect the pharmacokinetics of tesaglitazar, a novel dual peroxisome proliferator-activated receptor alpha/gamma agonist. | Samuelsson S et al. | β | 2006 | β |
| Inhibition of smooth muscle proliferation by urea-based alkanoic acids via peroxisome proliferator-activated receptor alpha-dependent repression of cyclin D1. | Ng VY et al. | β | 2006 | β |
| Investigational PPAR-gamma agonists for the treatment of Type 2 diabetes. | Savkur RS et al. | β | 2006 | β |
| Overview of nomenclature of nuclear receptors. | Germain P et al. | β | 2006 | β |
| Permuting input for more effective sampling of 3D conformer space. | Carta G et al. | β | 2006 | β |
| Pharmacological characterization of hydrolysis-resistant analogs of oleoylethanolamide with potent anorexiant properties. | Astarita G et al. | β | 2006 | β |
| Recombinant human PPAR-beta/delta ligand-binding domain is locked in an activated conformation by endogenous fatty acids. | Fyffe SA et al. | β | 2006 | β |
| Screening drug-like compounds by docking to homology models: a systematic study. | Kairys V et al. | β | 2006 | β |
| Selective PPAR modulators, dual and pan PPAR agonists: multimodal drugs for the treatment of type 2 diabetes and atherosclerosis. | Pourcet B et al. | β | 2006 | β |
| Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis. | Lefebvre P et al. | β | 2006 | β |
| Spectroscopic analyses of the binding kinetics of 15d-PGJ2 to the PPARgamma ligand-binding domain by multi-wavelength global fitting. | Shiraki T et al. | β | 2006 | β |
| Structure-based design of indole propionic acids as novel PPARalpha/gamma co-agonists. | Kuhn B et al. | β | 2006 | β |
| Structure-based drug design of a novel family of PPARgamma partial agonists: virtual screening, X-ray crystallography, and in vitro/in vivo biological activities. | Lu IL et al. | β | 2006 | β |
| Very-long-chain and branched-chain fatty acyl-CoAs are high affinity ligands for the peroxisome proliferator-activated receptor alpha (PPARalpha). | Hostetler HA et al. | β | 2006 | β |
| 2-Alkoxydihydrocinnamates as PPAR agonists. Activity modulation by the incorporation of phenoxy substituents. | MartΓn JA et al. | β | 2005 | β |
| Alpha,beta-unsaturated ketone is a core moiety of natural ligands for covalent binding to peroxisome proliferator-activated receptor gamma. | Shiraki T et al. | β | 2005 | β |
| A restraint molecular dynamics and simulated annealing approach for protein homology modeling utilizing mean angles. | MΓΆglich A et al. | β | 2005 | β |
| Conformational adaptation of nuclear receptor ligand binding domains to agonists: potential for novel approaches to ligand design. | Togashi M et al. | β | 2005 | β |
| DASH: a novel analysis method for molecular dynamics simulation data. Analysis of ligands of PPAR-gamma. | Salt DW et al. | β | 2005 | β |
| Design and synthesis of alpha-aryloxyphenylacetic acid derivatives: a novel class of PPARalpha/gamma dual agonists with potent antihyperglycemic and lipid modulating activity. | Shi GQ et al. | β | 2005 | β |
| Drugs on the horizon for diabesity. | Bailey CJ | β | 2005 | β |
| Ertiprotafib improves glycemic control and lowers lipids via multiple mechanisms. | Erbe DV et al. | β | 2005 | β |
| Identification of putative metabolites of docosahexaenoic acid as potent PPARgamma agonists and antidiabetic agents. | Yamamoto K et al. | β | 2005 | β |
| Is antagonism of E/Z-guggulsterone at the farnesoid X receptor mediated by a noncanonical binding site? A molecular modeling study. | Meyer U et al. | β | 2005 | β |
| Ligand control of coregulator recruitment to nuclear receptors. | Nettles KW et al. | β | 2005 | β |
| Novel 2,3-dihydrobenzofuran-2-carboxylic acids: highly potent and subtype-selective PPARalpha agonists with potent hypolipidemic activity. | Shi GQ et al. | β | 2005 | β |
| Nuclear receptor antagonists designed based on the helix-folding inhibition hypothesis. | Hashimoto Y et al. | β | 2005 | β |
| Peroxisome proliferator-activated receptor alpha interacts with high affinity and is conformationally responsive to endogenous ligands. | Hostetler HA et al. | β | 2005 | β |
| Stability of fatty acyl-coenzyme A thioester ligands of hepatocyte nuclear factor-4alpha and peroxisome proliferator-activated receptor-alpha. | Schroeder F et al. | β | 2005 | β |
| Structural characteristics of lysophosphatidic acid biological targets. | Parrill AL | β | 2005 | β |
| Sulfur-substituted and alpha-methylated fatty acids as peroxisome proliferator-activated receptor activators. | Larsen LN et al. | β | 2005 | β |
| Synthesis and biological evaluation of new clofibrate analogues as potential PPARalpha agonists. | Perrone MG et al. | β | 2005 | β |
| Synthesis, biological evaluation, and molecular modeling investigation of new chiral fibrates with PPARalpha and PPARgamma agonist activity. | Pinelli A et al. | β | 2005 | β |
| Tesaglitazar, a dual PPAR{alpha}/{gamma} agonist, ameliorates glucose and lipid intolerance in obese Zucker rats. | Oakes ND et al. | β | 2005 | β |
| The conserved residue Phe273(282) of PPARalpha(gamma), beyond the ligand-binding site, functions in binding affinity through solvation effect. | Yue L et al. | β | 2005 | β |
| 1. Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands and their therapeutic utility. | Henke BR | β | 2004 | β |
| (2R)-2-ethylchromane-2-carboxylic acids: discovery of novel PPARalpha/gamma dual agonists as antihyperglycemic and hypolipidemic agents. | Koyama H et al. | β | 2004 | β |
| A new class of peroxisome proliferator-activated receptor agonists with a novel binding epitope shows antidiabetic effects. | Ostberg T et al. | β | 2004 | β |
| A novel selective peroxisome proliferator-activated receptor alpha agonist, 2-methyl-c-5-[4-[5-methyl-2-(4-methylphenyl)-4-oxazolyl]butyl]-1,3-dioxane-r-2-carboxylic acid (NS-220), potently decreases plasma triglyceride and glucose levels and modifies lipoprotein profiles in KK-Ay mice. | Kuwabara K et al. | β | 2004 | β |
| Binding analyses between Human PPARgamma-LBD and ligands. | Yu C et al. | β | 2004 | β |
| [Design and synthesis of subtype- and species-selective peroxisome proliferator-activated receptor (PPAR) alpha ligands]. | Miyachi H | β | 2004 | β |
| Design, synthesis, and evaluation of a new class of noncyclic 1,3-dicarbonyl compounds as PPARalpha selective activators. | Li Z et al. | β | 2004 | β |
| Peroxisome proliferator-activated receptor alpha/gamma dual agonists for the treatment of type 2 diabetes. | Henke BR | β | 2004 | β |
| Peroxisome proliferator-activated receptor (PPAR) activation induces tissue-specific effects on fatty acid uptake and metabolism in vivo--a study using the novel PPARalpha/gamma agonist tesaglitazar. | Hegarty BD et al. | β | 2004 | β |
| Pharmacological characterization of a human-specific peroxisome proliferater-activated receptor alpha (PPARalpha) agonist in dogs. | Nagasawa M et al. | β | 2004 | β |
| Sphingosine 1-phosphate and lysophosphatidic acid receptors: agonist and antagonist binding and progress toward development of receptor-specific ligands. | Parrill AL et al. | β | 2004 | β |
| Analysis of the critical structural determinant(s) of species-selective peroxisome proliferator-activated receptor alpha (PPAR alpha)-activation by phenylpropanoic acid-type PPAR alpha agonists. | Miyachi H et al. | β | 2003 | β |
| Coactivator binding promotes the specific interaction between ligand and the pregnane X receptor. | Watkins RE et al. | β | 2003 | β |
| Crystal structure of the human liver X receptor beta ligand-binding domain in complex with a synthetic agonist. | Hoerer S et al. | β | 2003 | β |
| Design and synthesis of novel PPARalpha/gamma/delta triple activators using a known PPARalpha/gamma dual activator as structural template. | Mogensen JP et al. | β | 2003 | β |
| Design, synthesis, and evaluation of substituted phenylpropanoic acid derivatives as human peroxisome proliferator activated receptor activators. Discovery of potent and human peroxisome proliferator activated receptor alpha subtype-selective activators. | Nomura M et al. | β | 2003 | β |
| Homology modelling of the nuclear receptors: human oestrogen receptorbeta (hERbeta), the human pregnane-X-receptor (PXR), the Ah receptor (AhR) and the constitutive androstane receptor (CAR) ligand binding domains from the human oestrogen receptor alpha (hERalpha) crystal structure, and the human peroxisome proliferator activated receptor alpha (PPARalpha) ligand binding domain from the human PPARgamma crystal structure. | Jacobs MN et al. | β | 2003 | β |
| Large dimeric ligands with favorable pharmacokinetic properties and peroxisome proliferator-activated receptor agonist activity in vitro and in vivo. | Sauerberg P et al. | β | 2003 | β |
| Molecular basis for the subtype discrimination of the estrogen receptor-beta-selective ligand, diarylpropionitrile. | Sun J et al. | β | 2003 | β |
| [New antilipemics: prospects]. | Farnier M | β | 2003 | β |
| Novel peroxisome proliferator-activated receptor ligands for Type 2 diabetes and the metabolic syndrome. | Miller AR et al. | β | 2003 | β |
| Peroxisome proliferator-activated receptors target family landscape: a chemometrical approach to ligand selectivity based on protein binding site analysis. | Pirard B | β | 2003 | β |
| Synthesis and biological and structural characterization of the dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist ragaglitazar. | Ebdrup S et al. | β | 2003 | β |
| AZ 242, a novel PPARalpha/gamma agonist with beneficial effects on insulin resistance and carbohydrate and lipid metabolism in ob/ob mice and obese Zucker rats. | Ljung B et al. | β | 2002 | β |
| Enantio-dependent binding and transactivation of optically active phenylpropanoic acid derivatives at human peroxisome proliferator-activated receptor alpha. | Miyachi H et al. | β | 2002 | β |
| Fluorescence-based ligand-binding assays for peroxisome proliferator-activated receptors. | Adamson DJ et al. | β | 2002 | β |
| Molecular modelling of the peroxisome proliferator-activated receptor alpha (PPAR alpha) from human, rat and mouse, based on homology with the human PPAR gamma crystal structure. | Lewis DF et al. | β | 2002 | β |
| Peroxisome proliferator-activated receptor agonists, hyperlipidaemia, and atherosclerosis. | Vosper H et al. | β | 2002 | β |
| Physiological and therapeutic roles of peroxisome proliferator-activated receptors. | Berger J et al. | β | 2002 | β |
| Antagonism of the actions of peroxisome proliferator-activated receptor-alpha by bile acids. | Sinal CJ et al. | β | 2001 | β |