Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 21 for “"inverse agonist"”.
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Characterization of Novel Liver X Receptor Inverse Agonist in Breast Cancers
… metabolism. Moreover, LXR inhibition using the inverse agonist SR9243 has been shown to disrupt glycolysis, de novo lipogenesis, and induce antitumor immunity. In our lab, we discovered another cancer-specific LXR inverse agonist, GAC0001E5 (1E5), in pancreatic ductal adenocarcinoma (PDAC). …
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Cannabinoid Receptor 2 (CB2) Ligands Downregulate Pro-Inflammatory Markers in Stimulated Primary Human Periodontal Ligament Fibroblasts (hPDLFs)
… inflammation. Our lead compound SMM-189 is a CB2 inverse agonist, which exhibited anti-inflammatory properties in various primary cell lines. We aimed to address the anti-inflammatory properties seen with cannabinoid synthetic compounds SMM-189 (CB2 selective inverse agonist), HU308 (CB2 selective …
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Characterization of Rimonabant effects on G protein activity
… in the pharmaceutical market. In the absence of agonists, many GPCRs have found to exhibit spontaneous activity, which can be blocked by ligands that are referred to as inverse agonists (Milligan, 2003). Cannabinoid CB1 receptor is one of the most abundant GPCR in the central nervous system, and …
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Validation of ACTOne CB1 and CB2 Assays, Subsequent Characterization of SMM-189, and Development and Characterization of New CB2 Inverse Agonists
… and efficacy, and for selected compounds, antagonist activity. Our lead compound, SMM-189, was evaluated using the ACTOne assays and determined to be a CB2 inverse agonist. Further investigation revealed SMM-189 to exert anti-inflammatory effects on the brain’s immune cells, microglia, through …
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Synthesis of Novel Cannabinoid Ligands and Their Use as Anti-Glioma and Anti-Inflammatory Agents
… lead compounds for these studies: KM-233 (CB2 antagonist) and HB-I-172 (CB2 inverse agonist). Both compounds showed <em>in vitro </em>efficacy against four human glioma cell lines (EC<sub>50</sub>s = 2.27 ± 0.18µM to 6.34 ± 4.10µM) while HB-I-172 also showed efficacy against prostate, lung, and …
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Neurobiologically-motivated treatments for post-traumatic stress disorder in an animal model
… Chronic exposure to a ghrelin receptor agonist, without stress, enhanced associational fear learning without altering HPA hormone levels. This effect was replicated by repeated direct infusions of a ghrelin receptor agonist in the basolateral amygdala (BLA), a brain region involved in …
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Caratterizzazione del clofibrato agonista sintetico dei recettori dei proliferatori dei perossisomi (PPARα)in modelli animali di depressione ed ansia
… antidepressant-like effect of synthetic PPARα agonists. Thus, the aim of our study was to characterize the pharmacological profile of synthetic PPARα agonists as clofibrate by motor activity test to evaluate possible motor impairments, the forced swim test (FST) for the antidepressant activity, …
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Strategies to Identify Therapeutic Opportunities in the Treatment of Addictive Disorders
… serotonin (5-HT) 5-HT2A receptor (5-HT2AR) antagonist/inverse agonist pimavanserin and 5-HT2CR agonist lorcaserin used alone or in combination demonstrate efficacy in suppressing measures of binge eating. Pharmacological studies further show that activation of the 5-HT2CR may suppress binge …
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Lipid sensitivity of the GPR132 receptor
… transmembrane domain 5 was found to switch full agonist behaviour of a synthetic ligand towards an inverse agonist. Altogether, the experiments outlined in this thesis may prove useful in the design of potent antagonists for this receptor.
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Design, Synthesis and Biological Evaluation of Novel Cannabinoid Antagonist
… diaryl group revealed in the prototypical antagonist/inverse agonist SR141716 (Rimonabant) that was presumed to interact with a unique region in the CB1 receptors. Based on our preliminary results we identified a novel series of 1,2,3-triazole ester and keto derivatives as lead compounds …
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Constitutive activity in orphan G protein coupled receptors
… pathway analysis to evaluate the extent of agonist independent constitutive signaling among orphan class-A G protein coupled receptors (GPCRs). These receptors translate extracellular signals via conformational change into intracellular activation of different G proteins and subsequent …
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An Investigation into the pharmacology of the ghrelin receptor
… and L-692,429 were reported to act both as co-agonists (increasing the efficacy of the ghrelin response) and as negative or positive (respectively) regulators of the potency of ghrelin. This study sought to investigate the pharmacology of the GRLN-R through the Gai/o pathway. [35S]GTPyS binding …
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INHIBITING THE NUCLEAR RECEPTOR ESRRA RESCUES CORE PATHOLOGIES IN CELLULAR AND ANIMAL MODELS OF BATTEN DISEASE
… and pharmacological inhibition of ESRRA with the inverse agonist XCT-790 significantly reduced Gb3 accumulation in both CLN3 and CLN7 disease models, suggesting that ESRRA may represent a novel therapeutic target for multiple BDs. Transcriptomic analysis revealed that pharmacological inhibition of …
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The Serotonin (5-HT) 5-HT2A Receptor is a Priority Target to Reduce Impulsive Action in Substance Use Disorders: Preclinical Evidence
… studies with investigational 5-HT2AR antagonists/inverse agonists. We first established the potential for repurposing the recently FDA-approved 5-HT2AR antagonist/inverse agonist pimavanserin (Nuplazid®) as a therapeutic to forestall relapse vulnerability in cocaine use disorder (CUD). …
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Protein-ligand interaction studies and identification of new drug-like hits as cannabinoid receptor modulators
… receptors, (2) the identification of novel CB1 inverse agonists, and (3) the identification of allosteric site(s) in the CB2 receptor and screening of new CB2 allosteric modulators (AMs).</p> <p>Chapter 1 describes background information on cannabinoids and the endocannabinoid system. Chapter 2 …
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The human cannabinoid CB(1) receptor stably expressed in Chinese hamster ovary cells provides a model system to predict the pharmacological effects of cannabinoids in man
… expression system is able to differentially bind agonists (CP55,940) and antagonists (SR141716A). In the [³⁵S]GTPγS binding assay, CP55,940, WIN 55,212-2 and HU-210 are full agonists, methanandamide and 11-OH-Δ⁹-THC are partial agonists, Δ⁹-THC is a competitive antagonist and SR141716A and AM630 …
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Studies investigating the mechanisms of the cardioprotective effects of Cannabidiol.
… but is not limited to, an ability to act as an inverse agonist at the CB1 and CB2 receptors and an antagonist of GPR55. Moreover, is has been shown to reduce infarct size and ameliorate reductions in left ventricular function in vivo. These improvements in the pathogenesis of experimental MI are …
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Cognitive and synaptic dysfunction in a mouse model of Huntington's disease
… treatment with the a5-GABAA receptors selective inverse agonist a5IA. <br/><br/>Importantly, the clinically relevant heterozygous HdhQ111 mice exhibited an identical phenotype to homozygous HdhQ111 mice indicating that, reminiscent of the human disorder, only one copy of the mutant gene is …
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Possibile ruolo del sistema endocannabinoide nel disturbo d’alimentazione incontrollata (binge eating disorder): studi comportamentali, farmacologici e biochimici
… neurotransmitter release. CB1 receptors inverse agonists inhibit food intake through both central and peripheral mechanisms while, in contrast, cannabinoid agonists stimulate food intake in humans and induce beneficial effects in acquired immune deficiency syndrome related to anorexia, …
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Development and Characterization of Selective CB2R Inverse Agonists as a Novel Anti-Inflammatory Therapy for Neuroinflammation – Mechanisms of Action in Murine and Human Microglia Models Provide Valuable Insights into Their Therapeutic Potential
… affinities to CB2R were further assessed in antagonist (competition) studies against the non-selective cannabinoid agonist CP 55,940. Compound 45 demonstrated CB2R inverse agonism at G-protein signaling with high potency, efficacy, and affinity in the binding and functional assays and was …
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