A5067468660- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Receptor Mechanisms and Signaling
- Photosynthetic Processes and Mechanisms
- Neuroscience and Neuropharmacology Research
- Nicotinic Acetylcholine Receptors Study
- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Hearing, Cochlea, Tinnitus, Genetics
- Pharmacological Effects and Assays
- Asthma and respiratory diseases
- Vestibular and auditory disorders
- Cardiac Arrest and Resuscitation
- Neurotransmitter Receptor Influence on Behavior
- Photoreceptor and optogenetics research
- Pharmaceutical studies and practices
- Chemical Synthesis and Analysis
- Coenzyme Q10 studies and effects
- Metabolism and Genetic Disorders
- Memory and Neural Mechanisms
- Neuropeptides and Animal Physiology
- Mechanical Circulatory Support Devices
- Thermal Regulation in Medicine
- Pharmacological Effects and Toxicity Studies
- Respiratory and Cough-Related Research
Novartis (Switzerland)
2013-2024
Novartis Institutes for BioMedical Research
2013-2021
Novartis (United States)
2021
Novartis (India)
2021
Aix-Marseille Université
1978-2016
McGill University
1962-2014
University Children's Hospital Zurich
2008
Novartis (France)
2006
University Hospital Ulm
2006
Universität Ulm
2006
The adenosine A 2a receptor belongs to the seven transmembrane helix G‐protein‐coupled family, is abundant in striatum, vasculature and platelets involved several physiological processes such as blood pressure regulation protection of cells during anoxia. For structural biophysical studies we have expressed human (hA2aR) at high levels inserted into Escherichia coli inner membrane, established a purification scheme. Expression was fusion with periplasmic maltose‐binding protein 10–20 nmol...
The bisphosphonate zoledronic acid is a potent inhibitor of osteoclast-mediated bone resorption. To investigate drug biodistribution and elimination, <sup>14</sup>C-zoledronic was administered intravenously to rats dogs in single or multiple doses assessed for its vitro blood distribution plasma protein binding rat, dog, human. Drug exposure plasma, bones, noncalcified tissues investigated up 240 days 96 h using radiometry after dissection. the rat within selected bones from dog by...
The precursor proteins to the subunits of ubiquinol:cytochrome c reductase (cytochrome bc1 complex) Neurospora crassa were synthesized in a reticulocyte lysate. These precursors immunoprecipitated with antibodies prepared against individual and compared mature or isolated from mitochondria. Most as larger apparent molecular weights (subunits I, 51,500 versus 50,000; subunit II, 47,500 45,000; IV c1), 38,000 31,000; V (Fe-S protein), 28,000 25,000; VII, 12,000 11,500; VIII, 11,600 11,200)....
Active peptide helices : The β‐nonapeptide H‐β 3 HPhe‐β 2 HVal‐β HLeu‐β HLys‐β HPhe‐OH with alternating β ‐ and ‐amino‐acid residues has been tested for antibiotic hemolytic activities. This represents the first case of biomimetic activity a “mixed” /β ‐peptide.
The methylotrophic yeast Pichia pastoris was tested for heterologous expression of the mouse 5‐HT 5A receptor. Three different plasmids were constructed where cDNA receptor cloned under transcriptional control highly inducible promotor P. alcohol oxidase 1 (AOX1) gen. differed with respect to signal sequences used N‐terminal fusion. In two cases coding region additionally fused c‐ myc tag permit immunological detection Expression functional after transformation strain GS115 detected by...
Over the last few years, Pichia pastoris has been developed into a powerful expression system for multitude of foreign genes. Here, we demonstrate that P. similar power to baculovirus in high-level production two G-protein-coupled receptors, mouse 5HT5A 5-hydroxtryptamine receptor and human β2-adrenergic receptor. Different plasmids were constructed which cDNAs receptors cloned under transcriptional control highly inducible promoter alcohol oxidase 1 (AOX1) gene. In three plasmids, fused...
Aims To determine blood binding parameters of imatinib and its metabolite CGP74588 in humans non‐human species. Methods The distribution protein were determined vitro using 14 C labelled compounds. Results mean fraction plasma (f p ) was 45% dog, 50% mouse, 65% rat, 70% healthy up to 92% acute lymphatic leukaemia (AML) patients. Similarly, f for low dog monkey (30%), higher mouse (70%) highest some AML patients (90%). unbound lower (2.3–6.5% at concentrations ≤ 5000 ng ml −1 compared...
The antibacterial activities of 31 different beta-, mixed alpha/beta-, and gamma-peptides, as well beta-peptides derived from beta2-3-aza- beta3-2-methylidene-amino acids were assayed against six pathogens (Enterococcus faecalis, Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Klebsiella Pseudomonas aeruginosa), the results compared with literature data. interaction these peptides mammalian cells, modeled by measuring hemolysis human erythrocytes, was also investigated. In...
Pimecrolimus and tacrolimus are calcineurin inhibitors used for the topical treatment of atopic dermatitis. Although structurally similar, they display specific differences including higher lipophilicity lower skin permeation pimecrolimus. The aim present study was to understand reason in permeation; addition, plasma protein binding two drugs analyzed side by as a basis comparison systemic exposure free drug. Permeation pimecrolimus through silicon membrane found be similar; therefore, we...
Background This phase 2 randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of nicotinic acetylcholine receptor α7 agonist AQW051 in patients with Parkinson's disease levodopa-induced dyskinesia. Methods Patients idiopathic moderate to severe dyskinesia were randomized 10 mg (n = 24), 50 or placebo 23) once daily for 28 days. Coprimary end points change Modified Abnormal Involuntary Movement Scale Unified Disease Rating part III scores. Secondary outcomes...
Journal Article Tracheal allograft replacement. An unsuccessful method Get access European of Cardio-Thoracic Surgery, Volume 7, Issue 12, December 1993, Pages 648–652, https://doi.org/10.1016/1010-7940(93)90261-9 Published: 01 1993
Activation of the α7 nicotinic ACh receptor (nACh receptor) is considered an attractive target for treatment cognitive impairment associated with neurological disorders. Here we describe novel α7-nACh agonist AQW051 as a promising drug candidate this indication.AQW051 was functionally characterized in vitro and effects evaluated rodent behavioural models. Pharmacokinetics tolerability were three phase I placebo-controlled studies 180 healthy subjects.In vitro, bound high affinity to...
LYS006 is a novel, highly potent and selective, new-generation leukotriene A4 hydrolase (LTA4H) inhibitor in clinical development for the treatment of neutrophil-driven inflammatory diseases. We describe complex pharmacokinetic to pharmacodynamic (PD) relationship blood, plasma, skin LYS006-treated nonclinical species healthy human participants. In randomized first study, participants were exposed single ascending doses up 100 mg multiple 80 b.i.d.. showed rapid absorption, overall dose...
Abstract The highly positively charged, cell‐penetrating β 3 ‐octaarginine has been prepared with a radioactive label by acetylation at the N‐terminus doubly 14 C‐labeled acetyl group ( CH CO). With compound, an ADME study A bsorption, D istribution, M etabolism, E xcretion) was performed in male rats following intravenous or oral dose of 1 mg/kg. Sampling carried out after periods ranging from 5 min to 4 d 7 for blood/excretia and quantitative whole‐body autoradioluminography (QWBA),...
We evaluated the pharmacokinetics (PK), safety, and tolerability of a novel oral CRTh2 antagonist, fevipiprant (QAW039), in healthy subjects. Peak concentrations plasma were observed 1-3 hours postdosing. Concentrations declined multiexponential manner, followed by an apparent terminal phase (t1/2 , ∼20 hours). Steady state was achieved 4 days with <2-fold accumulation. Elimination partly renal excretion (≤30% dose) glucuronidation. Food had minimal impact on PK fevipiprant, it well...