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 20 for “"Partial agonists"”.
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Defining Novel Clusters of PPAR gamma Partial Agonists for Virtual Screening
… mellitus (T2D). Thiazolidinediones (TZDs) are agonists of PPARγ which have an insulin sensitizing effect, and are therefore used as a treatment for T2D. However, TZDs cause negative side effects in patients, such as weight gain, edema, and increased risk of bone fracture. Partial agonists could …
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INVESTIGATION OF THE STRUCTURE AND FUNCTION OF GLUTAMATE RECEPTOR GLUR2 USING SOLUTION NMR SPECTROSCOPY
… a hypothesis directly relating the activity of a partial agonist with the degree of lobe closure of the soluble ligand binding domain (S1S2) observed upon binding that ligand. This hypothesis was based on analysis of x-ray crystal structures bound to a family of partial agonists, 5substituted …
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Understanding The Single Channel Behavior Of Glua3 Receptors
… ligand binding domain (LBD) bound to different agonists, partial agonists, and antagonists, were compared to whole cell electrophysiological recordings. A correlation between the degree of lobe closure and maximal currents was discovered; that is, the greater the degree of LBD closure, the …
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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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Conformational Dynamics of the Glutamate Receptors via single Molecule Förster Resonance Energy Transfer
… of the receptor to a variety of known full and partial agonists is tested. Additionally multiple receptor types are investigated to determine if the conformational pathway is conserved between the different types of glutamate receptors. The results from this project allows for a more complete …
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I. A Structure-Based Approach Toward the Development of a Ligand-Receptor System With Unique Specificity. II. Synthesis and Evaluation of Hexahydrochrysene and Tetrahydrobenzofluorene Derivatives as Selective Estrogen Receptor Modulators
… to mimick or antagonize estrogenic effects. Partial agonists, with a tissue selective agonist/antagonist profile, termed selective estrogen receptor modulators (SERMs), are better candidates for applications in the treatment of estrogen sensitive breast cancer and pathologies associated with …
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ALPHA4BETA2 NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS: FROM SUBTYPE SELECTIVE TO STOICHIOMETRIC ISOPHORM SELECTIVE PARTIAL AGONISM.
… and Ser108àAla mutants using the most promising partial agonists synthesized previously. The second goal was the synthesis and pharmacological evaluation of the naked and hydroxy/methoxy decorated benzofuran-based compound in order to study the implications of the flexibility reduction, …
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Computational modeling and simulation of ligand-gated ion channels
… human glycine receptor (GlyR), bound to full and partial agonists, in different functional states. In a collaborative work, MD simulations were used along with cryo-electron microscopy and electrophysiology to determine the structural models for the desensitized and open state GlyR bound to the …
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Cellular Mechanisms Underlying the Action of Melatonin in the Suprachiasmatic Nucleus
… was examined using the putative MT2 receptors antagonists 4P-PDOT and luzindole, it was found that these antagonists behaved as partial agonists for melatonin. To test the hypothesis that the circadian effect of melatonin on the SCN was due to receptor availability, the localization of MT1 and MT2 …
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Structure-function studies of agonist binding to the muscle-type nicotinic acetylcholine receptor and the development of a trifunctional non-competitive antagonist suitable for activity-dependent profiling
… and the dynamics of their interactions with agonists and competitive antagonists are still under investigation. These details are of particular importance to the design of AChR agonists, partial agonists, and competitive antagonists which may have therapeutic potential for treating …
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GPR55 and N-acyl Amino Acids
… occurring CB<sub>1</sub> and CB<sub>2</sub> agonists). N-acyl amino acids have little or no affinity for either CB<sub>1</sub> or CB<sub>2</sub> and many have no known biological target at present.</p> <p>This study used a subset of N-acyl amino acids; possessing either a serine or glycine …
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Molecular Regulation of Opioid Receptor Signaling
… receptor kinase (GRK) and arrestin. Therefore, a partial KOR agonist that does not efficiently activate arrestin-dependent signaling may produce analgesia without dysphoria. No selective KOR partial agonists are currently available, and preclinical assessment is complicated by sequence differences …
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Searching for structural determinants of agonist selectivity in nicotinic acetylcholine receptors
… nicotine (Nic). Activation of these receptors by partial agonists is considered as a valid strategy to intervene therapeutically in the aforementioned dysfunctions. For clinical scenarios such as Nic addiction receptor subtype-specificity may increase clinical efficacy by decreasing off-target …
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Functional characterisation of aphid, Myzus persicae, nicotinic acetylcholine receptors and identification of a novel biogenic amine-gated ion channel from the honeybee, Apis mellifera
… of 91.1 µM, upon which neonicotinoids acted as partial agonists. The Apis mellifera, European honeybee, α5 subunit formed a homomeric nAChR in oocytes without any chaperones. This was sensitive to 0.1 μM α-bungarotoxin and responded to both acetylcholine and choline but with low affinity, as …
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Synthesis of fluorinated cannabinoid derivatives; Towards PET radiotracers for imaging the cannabinoid receptor
… effects associated with CB1R orthosteric agonists remain a challenge to the development of novel cannabinoid-derived therapeutics leading to the development of GAT211 as CB1R-positive allosteric modulators (PAMs)5,6. In the second part of this project, we embarked on modifying structural …
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Characterisation of novel compounds as antagonists of protease-activated receptor-2 (PAR2)
… lack of potent and selective small-molecule antagonists. Recently, a number of new putative antagonists including GB88 and AZ8838 have been proposed to be effective in cells and in vivo. However, given the relative lack of information about these compounds this thesis examined the …
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Kinetic studies of the spasmogenic effects of serotonin and isolates from Byrsonima crassifolia leaves on rat fundus
… kinetics using cholinergics and 5-HT agonists and antagonists was carried out. 1-NP competitively antagonized 5-HT. The 5-HT, antagonist s-(-)propranolol did not significantly antagonize 5-HT. The 5-HT<sub>2</sub> blocker ketanserin noncompetitively antagonized 5-HT and …
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Molecular mechanism of action of the glucocorticoid receptor:Role of ligand-dependent receptor phosphorylation and half-life in determination of ligand-specific transcriptional activity. : Contents Pages
… Using a panel of twelve GR ligands, including agonists, partial agonists and antagonists, the relationship between the extent of GR phosphorylation at S226, GR turnover and transcriptional response, was investigated using a variety of biochemical approaches. Using a phospho-S226-specific GR …
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COMPOSTI AD AZIONE ANTI-AGGREGANTE ESERCITANO UN EFFETTO BENEFICO SU MODELLI CELLULARI DI ATROFIA MUSCOLARE SPINALE BULBARE
… system) six compounds, AR antagonist or partial agonists analogs, defined as SARMs (Selective AR Modulator), known to prevent the N/C interaction but to permit the nuclear receptor transcriptional activity. The treatment of our cells with this molecules indeed prevents the aggregation of …
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DISEASE-MODIFYING APPROACHES TO MULTIPLE SCLEROSIS: DESIGN AND SYNTHESIS OF NOVEL POTENTIAL THERAPEUTIC AGENTS
… set of derivatives was designed as putative partial agonists through modification of the pharmacophoric portion (PCD-1, PCD-2, PCD-3, PCD-4, PCD-5, PCD-6). Derivatives PCD-1, PCD-2 and PCD-3 showed the desired partial agonist activity, with a potency similar to the lead compound. Derivatives …