A5031121778- Receptor Mechanisms and Signaling
- Respiratory Support and Mechanisms
- Cardiac electrophysiology and arrhythmias
- Transplantation: Methods and Outcomes
- Neonatal Respiratory Health Research
- Computational Drug Discovery Methods
- Neuroscience and Neuropharmacology Research
- HIV Research and Treatment
- Ion channel regulation and function
- Sulfur Compounds in Biology
- Neuroscience of respiration and sleep
- Protein Kinase Regulation and GTPase Signaling
- HIV/AIDS drug development and treatment
- Phosphodiesterase function and regulation
- Pulmonary Hypertension Research and Treatments
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Nitric Oxide and Endothelin Effects
- Antibiotics Pharmacokinetics and Efficacy
- Asthma and respiratory diseases
- Neuropeptides and Animal Physiology
- Crystallization and Solubility Studies
- Fungal Infections and Studies
- Medical Imaging and Pathology Studies
- Mechanical Circulatory Support Devices
- Pleural and Pulmonary Diseases
Pfizer (United States)
2014-2024
Lindenhofspital
2023
Tanabe Research Laboratories
2019-2023
Great Ormond Street Hospital
2018
University College London
2018
Research Triangle Park Foundation
2003-2014
Pfizer (United Kingdom)
2002-2014
University of San Diego
2014
GlaxoSmithKline (United States)
2003-2010
GlaxoSmithKline (Netherlands)
2005
1. Long chain fatty acids have recently been identified as agonists for the G protein-coupled receptors GPR40 and GPR120. Here, we present first description of GW9508, a small-molecule agonist acid In addition, also describe pharmacology GW1100, selective antagonist. These molecules were used to further investigate role in glucose-stimulated insulin secretion MIN6 mouse pancreatic beta-cell line. 2. GW9508 linoleic both stimulated intracellular Ca2+ mobilization human embryonic kidney...
4-{[4-({(3R)-1-Butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-2,5dioxo-1,4,9-triazaspiro[5.5]undec-9-yl}methyl)phenyl]oxy}benzoic acid hydrochloride (873140) is a potent noncompetitive allosteric antagonist of the CCR5 receptor (pK(B) = 8.6 +/- 0.07; 95% CI, 8.5 to 8.8) with concomitantly antiviral effects for HIV-1. In this article, receptor-based mechanism action 873140 compared four other antagonists CCR5. Although...
Eosinophils are recruited to sites of inflammation via the action a number chemical mediators, including PAF, leukotrienes, eotaxins, ECF-A and histamine. Although many cell-surface receptors for these mediators have been identified, histamine-driven chemotaxis has not conclusively attributed any three known histamine receptor subtypes, suggesting possibility 4th histamine-responsive on eosinophils. We identified cloned novel G protein-coupled (GPCR), termed Pfi-013, from an IL-5 stimulated...
Insurmountable antagonism (maximal response to the agonist depressed) can result from a temporal inequilibrium involving slow offset orthosteric antagonist or be of an allosteric modulation receptor. The former mechanism is operative when antagonist, agonist, and receptors cannot come proper equilibrium during time allotted for collection (hemi-equilibrium conditions). Allosteric effects (changes in conformation receptor through binding modulator separate site) preclude agonist-induced...
<h3>Objective.</h3> —To evaluate the safety and potential efficacy of aerosolized surfactant in intubated patients with adult respiratory distress syndrome (ARDS). <h3>Design.</h3> —A prospective, double-blind, placebo-controlled, randomized, parallel, mutlicenter pilot clinical trial. <h3>Patients.</h3> total 51 sepsis-induced ARDS were entered into study within 18 hours developing sepsis or syndrome. <h3>Intervention.</h3> —Patients randomized four treatment groups a 2:1:2:1 ratio, as...
It is hypothesized that selective muscarinic M1 subtype activation could be a strategy to provide cognitive benefits schizophrenia and Alzheimer's disease patients while minimizing the cholinergic side effects observed with nonselective orthosteric agonists. Selective of positive allosteric modulator (PAM) has emerged as new approach achieve activation. This manuscript describes development series M1-selective pyridone pyridine amides their key pharmacophores. Compound 38 (PF-06767832) high...
Recent data demonstrated that activation of the muscarinic M1 receptor by a subtype-selective positive allosteric modulator (PAM) contributes to gastrointestinal (GI) and cardiovascular (CV) cholinergic adverse events (AEs) previously attributed M2 M3 activation. These studies were conducted using PAMs also exhibited agonist activity, leaving open possibility direct agonism, rather than modulation, could be responsible for effects. This article describes design synthesis lactam-derived...
Controversy has surrounded the use of single-lung transplantation (SLT) for treatment endstage obstructive lung disease. In recent years, several transplant centers have performed SLT such indications. this report, we describe functional results in patients undergoing disease, twenty-two followed over one year and 10 two years. Data include pulmonary function testing, gas exchange, quantitative ventilation perfusion to graft, symptom-limited graded cycle exercise testing after SLT. Our show...
Free radical activation and lipid peroxidation have been described in skeletal muscle during strenuous exercise. We hypothesized that oxygen radicals could also be formed the diaphragm resistive breathing these might affect function. Seven control 12 experimental male Sprague-Dawley rats were studied. Six animals subjected to (RB) alone six received 15 min of mechanical ventilatory support (MV) after period. Inspiratory resistance was adjusted maintain airway opening pressure at 70% maximum...
GSK812397 is a potent entry inhibitor of X4-tropic strains HIV-1, as demonstrated in multiple vitro cellular assays (e.g., peripheral blood mononuclear cells [PBMCs] and viral human osteosarcoma [HOS] assay, mean 50% inhibitory concentrations [IC50s]+/-standard errors the means were 4.60+/-1.23 nM 1.50+/-0.21 nM, respectively). The primary potency was not significantly altered by addition serum proteins (2.55 [+/-0.12]-fold shift presence albumin alpha-acid glycoprotein PBMC assay)....
Predicting ligand biological activity is a key challenge in drug discovery. Ligand-based statistical approaches are often hampered by noise due to undersampling: The number of molecules known be active or inactive vastly less than the possible chemical features that might determine binding. We derive framework inspired random matrix theory and combine with high-quality negative data discover important differences between disentangling undersampling noise. Our model outperforms standard...
The combined factors that regulate the expression of cell adhesion molecules (CAMs) during development nervous system are largely unknown. To identify such for Ng-CAM, neuron-glia CAM, constructs containing portions 5′ end Ng-CAM gene were examined activity after transfection into N2A neuroblastoma and NIH3T3 cells. Positive regulatory elements active in both types included an proximal promoter with SP1 cAMP response element motifs extending 447 base pairs upstream a single RNA start site...