scholarly journals (S)-1,2,3,4-Tetrahydroisoquinoline Derivatives Substituted with an Acidic Group at the 6-Position as a Selective Peroxisome Proliferator-Activated Receptor γ Partial Agonist

2019 ◽  
Vol 67 (11) ◽  
pp. 1211-1224
Author(s):  
Ko Morishita ◽  
Tomohiro Miike ◽  
Shigemitsu Takeda ◽  
Masaki Fukui ◽  
Yuma Ito ◽  
...  
Keyword(s):  
Partial Agonist ◽  
Peroxisome Proliferator ◽  
Acidic Group ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals CMHX008, a Novel Peroxisome Proliferator-Activated Receptor γ Partial Agonist, Enhances Insulin Sensitivity In Vitro and In Vivo

PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e102102 ◽  
Author(s):  
Yue Ming ◽  
Xiangnan Hu ◽  
Ying Song ◽  
Zhiguo Liu ◽  
Jibin Li ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Partial Agonist ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

A Novel Partial Agonist of Peroxisome Proliferator-Activated Receptor γ with Excellent Effect on Insulin Resistance and Type 2 Diabetes

2015 ◽  
Vol 353 (3) ◽  
pp. 573-581 ◽  
Author(s):  
Hui-juan Liu ◽  
Cheng-yu Zhang ◽  
Fei Song ◽  
Ting Xiao ◽  
Jing Meng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Partial Agonist ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Development of a Protocol for Virtual Screening of PPARγ Weak Partial Agonists and Their Metabolites: Case Study on Naturally-derived Oleanane Triterpenoids

2021 ◽  
Vol 25 (2) ◽  
pp. 117-132
Author(s):  
Merilin Al Sharif ◽  
◽  
Petko Alov ◽  
Vessela Vitcheva ◽  
Antonia Diukendjieva ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Molecular Mechanisms ◽  
Partial Agonist ◽  
Mechanistic Explanation ◽  
Binding Mode ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Partial Agonists ◽  
Docking Protocol ◽  
Agonistic Activity

Triterpenoids are well known metabolic syndrome (MetS) modulators. One of the suggested molecular mechanisms of action involves peroxisome proliferator-activated receptor gamma (PPARγ) activation. In this study we aimed to: (i) develop a virtual screening (VS) protocol for PPARγ weak partial agonists, (ii) predict potential metabolic transformations of naturally-derived triterpenoids, and (iii) perform VS of the triterpenoids and their metabolites. The NIH PubMed system was searched for publications about naturally-derived oleanane triterpenoids which are agonists or up-regulators of PPARγ. Structure- and ligand-based methods were combined in the development of the VS protocol. Metabolites were predicted using Meteor Nexus expert system (Lhasa Limited). Two in-house virtual libraries of PPARγ weak partial agonists and naturally-derived triterpenoids with their predicted metabolites were compiled. The pharmacophore-based docking protocol was applied for VS of the collected triterpenoids. Most of the docking poses reproduced the binding mode of caulophyllogenin (a weak partial agonist) in a complex with PPARγ (PDB ID 5F9B). Our results contribute to the mechanistic explanation of the effects of triterpenoids suggesting possible weak partial agonistic activity toward PPARγ. This research can direct further studies on triterpenoids’ role in MetS modulation. The developed protocol can be applied for VS of any PPARγ weak partial agonists.

scholarly journals A Novel Partial Agonist of Peroxisome Proliferator-Activated Receptor-γ (PPARγ) Recruits PPARγ-Coactivator-1α, Prevents Triglyceride Accumulation, and Potentiates Insulin Signaling in Vitro

2006 ◽  
Vol 20 (4) ◽  
pp. 809-830 ◽  
Author(s):  
Elke Burgermeister ◽  
Astride Schnoebelen ◽  
Angele Flament ◽  
Jörg Benz ◽  
Martine Stihle ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Partial Agonist ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Triglyceride Accumulation

Angiotensin II type 1 receptor blockade diminishes negative effect of chronic stress on memory via upregulation of brain-derived neurotrophic factor

2016 ◽  
Vol 33 (S1) ◽  
pp. S94-S94
Author(s):  
D. Wincewicz ◽  
A. Juchniewicz
Keyword(s):  
Gene Expression ◽  
Internal Control ◽  
Partial Agonist ◽  
Peroxisome Proliferator ◽  
Receptor Blockade ◽  
Peroxisome Proliferator Activated Receptor ◽  
Negative Effect ◽  
Competing Interest ◽  
Tata Box Binding Protein

IntroductionA critical need exists for progress in the characterization of targets for pro-cognitive drug discovery. We previously demonstrated that Telmisartan (TLM), an angiotensin type 1 receptor (AT1) blocker and partial agonist of peroxisome proliferator-activated receptor gamma (PPARγ), alleviates cognitive decline in chronically stressed rats. Understanding of mechanistic background of this phenomenon is hampered by both dual binding sites of TLM and limited data on the molecular consequences of central AT1 blockade and PPARγ activation.ObjectivesTo discriminate molecular effects of AT1 blockade and PPARγ activation in stress induced memory impairment.AimsIn this study, we investigated mechanism of neuroprotection provided by TLM in chronic psychological stress.MethodsWe analyzed BDNF gene expression in the hippocampus (HIP) and medial prefrontal cortex (mPFC) in chronically restrained stressed Wistar rats (2.5 h, 21 days), repeatedly treated with TLM (1 mg/kg), GW9662 (0.5 mg/kg) – a selective PPARγ receptor antagonist, or both in combination. TATA box binding protein (Tbp) was an internal control for expression studies.ResultsAlterations of mRNA expression of BDNF are shown on Figs. 1 and 2.ConclusionsAT1 receptor blockade restores cognitive functions in chronically stressed subjects, which is associated with changes in primarily cortical gene expression.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Telmisartan, a partial agonist of peroxisome proliferator-activated receptor γ, improves impairment of spatial memory and hippocampal apoptosis in rats treated with repeated cerebral ischemia

2010 ◽  
Vol 1353 ◽  
pp. 125-132 ◽  
Author(s):  
Tamami Haraguchi ◽  
Katsunori Iwasaki ◽  
Kotaro Takasaki ◽  
Kanako Uchida ◽  
Tetsuya Naito ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Spatial Memory ◽  
Partial Agonist ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hippocampal Apoptosis

scholarly journals L-764406 Is a Partial Agonist of Human Peroxisome Proliferator-activated Receptor γ

1999 ◽  
Vol 274 (12) ◽  
pp. 7913-7922 ◽  
Author(s):  
Alex Elbrecht ◽  
Yuli Chen ◽  
Alan Adams ◽  
Joel Berger ◽  
Patrick Griffin ◽  
...  
Keyword(s):  
Partial Agonist ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Galangin 3-benzyl-5-methylether derivatives function as an adiponectin synthesis-promoting peroxisome proliferator-activated receptor γ partial agonist

2021 ◽  
pp. 116564
Author(s):  
Hyejin Ko ◽  
Hongjun Jang ◽  
Seungchan An ◽  
In Guk Park ◽  
Sungjin Ahn ◽  
...  
Keyword(s):  
Partial Agonist ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals MBX-102/JNJ39659100, a Novel Peroxisome Proliferator-Activated Receptor-Ligand with Weak Transactivation Activity Retains Antidiabetic Properties in the Absence of Weight Gain and Edema

2009 ◽  
Vol 23 (7) ◽  
pp. 975-988 ◽  
Author(s):  
Francine M. Gregoire ◽  
Fang Zhang ◽  
Holly J. Clarke ◽  
Thomas A. Gustafson ◽  
Dorothy D. Sears ◽  
...  
Keyword(s):  
Target Genes ◽  
Partial Agonist ◽  
Oral Glucose ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Insulin Sensitizer ◽  
Glucose Lowering ◽  
Ppar Γ ◽  
Primary Mouse

Abstract MBX-102/JNJ39659100 (MBX-102) is in clinical development as an oral glucose-lowering agent for the treatment of type 2 diabetes. MBX-102 is a nonthiazolidinedione (TZD) selective partial agonist of peroxisome proliferator-activated receptor (PPAR)-γ that is differentiated from the TZDs structurally, mechanistically, preclinically and clinically. In diabetic rodent models, MBX-102 has insulin-sensitizing and glucose-lowering properties comparable to TZDs without dose-dependent increases in body weight. In vitro, in contrast with full PPAR-γ agonist treatment, MBX-102 fails to drive human and murine adipocyte differentiation and selectively modulates the expression of a subset of PPAR-γ target genes in mature adipocytes. Moreover, MBX-102 does not inhibit osteoblastogenesis of murine mesenchymal cells. Compared with full PPAR-γ agonists, MBX-102 displays differential interactions with the PPAR-γ ligand binding domain and possesses reduced ability to recruit coactivators. Interestingly, in primary mouse macrophages, MBX-102 displays enhanced antiinflammatory properties compared with other PPAR-γ or α/γ agonists, suggesting that MBX-102 has more potent transrepression activity. In summary, MBX-102 is a selective PPAR-γ modulator with weak transactivation but robust transrepression activity. MBX-102 exhibits full therapeutic activity without the classical PPAR-γ side effects and may represent the next generation insulin sensitizer.

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