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39 items found for "Orthostatic intolerance"
- Therapeutic validation of an orphan G protein-coupled receptor: The case of GPR84
August 2022 "Despite the importance of members of the GPCR superfamily as targets of a broad range of effective medicines many GPCRs remain poorly characterised. GPR84 is an example. Expression of GPR84 is strongly up regulated in immune cells in a range of pro-inflammatory settings and clinical trials to treat idiopathic pulmonary fibrosis are currently ongoing using ligands with differing levels of selectivity and affinity as GPR84 antagonists. Although blockade of GPR84 may potentially prove effective also in diseases associated with inflammation of the lower gut there is emerging interest in defining if agonists of GPR84 might find utility in conditions in which regulation of metabolism or energy sensing is compromised. Here, we consider the physiological and pathological expression profile of GPR84 and, in the absence of direct structural information, recent developments and use of GPR84 pharmacological tool compounds to study its broader role and biology. " Read more at the source #DrGPCR #GPCR #IndustryNews
- Targeting Intracellular Allosteric Sites in GPCRs
Conventional GPCR drug discovery has largely focused on orthosteric sites, but recent breakthroughs in Unlike orthosteric ligands that bind directly to the receptor's active site, allosteric modulators target sites on the receptor are those topographically distinct from (do not exhibit any overlap with) the orthosteric binding pocket, potentially altering the rate of association, dissociation, or both, of an orthosteric On the other hand, selectivity could be achieved by merging both orthosteric and allosteric pharmacophores
- GPCRs are not simple on-off switches: deep dive into GPCR-ligand interactions
GPCR targeting drugs: orthosteric vs allosteric sites Most of the drugs targeting GPCRs bind to the orthosteric sites on the receptor are those topographically distinct from (do not exhibit any overlap with) the orthosteric employing an allosteric mechanism of action can theoretically offer several advantages compared to orthosteric On the other hand, selectivity could be achieved by merging both orthosteric and allosteric pharmacophores of reducing the risk of overdose, given that their activity is dependent on the concentration of the orthosteric
- 📰 GPCR Weekly News, June 17 to 23, 2024
ovarian cancer cells by targeting PAR-1 G protein-coupled receptors related to autoimmunity in postural orthostatic
- Free-Energy Simulations Support a Lipophilic Binding Route for Melatonin Receptors
Crystal structures suggest ligand access to the orthosteric binding site of MT1 and MT2 receptors through simulations are consistent with the possibility that the gap between TM IV and V is a way of connecting the orthosteric
- Allosteric modulation of GPCRs: From structural insights to in silico drug discovery
programs have focused on the development of ligands targeting the binding site of endogenous ligands (orthosteric
- Helix 8 in chemotactic receptors of the complement system
Orthosteric and allosteric antagonists of C5aR1 are a novel strategy for anti-inflammatory therapies.
- Targeting mGluR2/3 for treatment of neurodegenerative and neuropsychiatric diseases
We then highlight the evidence supporting the use of various drugs including orthosteric and allosteric
- Pepducin-mediated G Protein-Coupled Receptor Signaling in the Cardiovascular System
pepducins have progressed initially from pharmacologic tools used to manipulate GPCR activity in an orthosteric
- Precise druggability of the PTH type 1 receptor
protein-coupled receptors (GPCRs) are notoriously difficult to target by small molecules because their large orthosteric
- Luciferase-based GloSensor™ cAMP assay: Temperature optimization and application to cell-based kinet
Monitoring intracellular cAMP levels can help identify orthosteric agonists and antagonists, as well
- In Vitro and In Silico Characterization of Kurarinone as a Dopamine D 1A Receptor Antagonist and ...
binding energies during the intermolecular interactions of kurarinone with the key residues of the deep orthosteric
- TM5-TM6: structural switches that modulate the coupling of serotonin receptors to Gs or Gi
The discovery of the orthosteric binding pocket is of great importance in GPCRs field as it supports
- 📰 GPCR Weekly News, January 23 to 29, 2023
Molecular Modeling Study of a Receptor-Orthosteric Ligand-Allosteric Modulator Signaling Complex.
- Therapeutic validation of an orphan G protein‐coupled receptor
Among these ligands are orthosteric agonists such as alkylpyrimidine‐4,6‐diol derivatives (Liu et al.
- 📰 GPCR Weekly News, September 25 to October 1, 2023
mechanisms by NMR spectroscopy with stable-isotope labeled receptors GPCR Binders, Drugs, and more Orthosteric
- Decoding GPCR Function: The Role of Mutagenesis in Rational Drug Discovery
Extracellular loop 2 of the adenosine A1 receptor has a key role in orthosteric ligand affinity and agonist
- 📰 GPCR Weekly News, November 13 to 19, 2023
ligase adaptor for substrate linear polyubiquitination GPCR Binders, Drugs, and more Dual allosteric and orthosteric
- Recurrent hypoglycemia increases hepatic gluconeogenesis without affecting glycogen metabolism or sy
Further, we performed pyruvate and lactate tolerance tests to assess gluconeogenesis. Finally, we conducted epinephrine tolerance test to investigate systemic glycemic excursions to counterregulatory
- In vivo metabolic effects after acute activation of skeletal muscle G s signaling
Results: Acute stimulation of GsD signaling in SKM impaired glucose tolerance in lean and obese mice Clenbuterol injection improved glucose tolerance by increasing insulin secretion in lean mice. UCN2 injection resulted in decreased glucose tolerance associated with lower plasma insulin levels.
- Trevena Announces Advancement of TRV045 Into Clinical Development for Diabetic Neuropathic Pain
2021 "3-part randomized, double-blind, placebo-controlled Phase 1 study will evaluate TRV045 safety, tolerability
- Inversago Pharma Completes Phase 1 Clinical Trial on First-in-Class, Peripheral CB1 Blocker and...
Favorable safety, tolerability and pharmacokinetic results from the trial warrant further investigation
- Search for safer pain relief advances with new engineered compounds
November 2021 " Chronic use of most opioids causes tolerance; the new compounds avoid this and other
- Artificial intelligence – faster, smarter, cheaper GPCR drug discovery
Predicting GPCR properties: AI models can predict various properties of GPCRs, such as ligand binding sites (orthosteric
- Karuna Therapeutics Announces Positive Results from Phase 3 EMERGENT-2 Trial of KarXT in...
announced positive topline results from its Phase 3 EMERGENT-2 trial evaluating the efficacy, safety, and tolerability
- Neurocrine Biosciences Announces Positive Phase 3 Data for KINECT-HD Study Evaluating Valbenazine...
announced positive top-line data from its Phase 3 KINECT-HD study evaluating the efficacy, safety and tolerability
- Confo Therapeutics Doses First Subjects In Phase 1 Clinical Trial Of CFTX-1554 For The Treatment ...
The Phase 1 study will assess the safety, tolerability and pharmacokinetics of CFTX-1554 in healthy subjects
- Targeted Therapies to Reduce Side Effects in Modern Drug Development
drugs to evaluated for potential toxicities and side effects, and these key factors must be deemed tolerable