A5085135927- Tuberculosis Research and Epidemiology
- Immune responses and vaccinations
- Asthma and respiratory diseases
- Pharmacogenetics and Drug Metabolism
- Mast cells and histamine
- Mycobacterium research and diagnosis
- Receptor Mechanisms and Signaling
- Stress Responses and Cortisol
- Synthesis and Biological Evaluation
- vaccines and immunoinformatics approaches
- Chemical Reactions and Isotopes
- Neonatal Respiratory Health Research
- Drug Transport and Resistance Mechanisms
- Tryptophan and brain disorders
- Immune Response and Inflammation
- Cystic Fibrosis Research Advances
- Metabolomics and Mass Spectrometry Studies
- Inhalation and Respiratory Drug Delivery
- Synthesis of heterocyclic compounds
- Science Education and Perceptions
- Protein Interaction Studies and Fluorescence Analysis
- Hippo pathway signaling and YAP/TAZ
- Escherichia coli research studies
- Synthesis and biological activity
- Diagnosis and treatment of tuberculosis
Animal and Plant Health Agency
2017-2024
Novartis Institutes for BioMedical Research
2014-2023
Novartis (Switzerland)
2007-2023
Novartis (United Kingdom)
2014-2015
The inhibition of the YAP-TEAD protein-protein interaction constitutes a promising therapeutic approach for treatment cancers linked to dysregulation Hippo signaling pathway. identification class small molecules which potently inhibit by binding tightly Ω-loop pocket TEAD has previously been communicated. This report details further multi-parameter optimization this compounds resulting in advanced analogs combining nanomolar cellular potency with balanced ADME and off-target profile,...
Some Aspects of the Pharmacology, Metabolism, and Toxicology Ibuprofen S. Adams, Adams Search for other works by this author on: Oxford Academic PubMed Google Scholar R. G. Bough, Bough E. Cliffe, Cliffe W. Dickinson, Dickinson B. Lessel, Lessel K. F. McCullough, McCullough N. Mills, Mills J. Nicholson, Nicholson A. H. Williams Rheumatology, Volume 10, Issue suppl_1, January 1970, Pages 9–22, https://doi.org/10.1093/rheumatology/X.suppl_1.9 Published: 01 1970
The European badger (Meles meles) is a reservoir host of Mycobacterium bovis and responsible for proportion the tuberculosis (TB) cases seen in cattle United Kingdom Republic Ireland. An injectable preparation bacillus Calmette-Guérin (BCG) vaccine licensed use badgers UK its forms part bovine TB eradication plans England Wales. However, there are practical limitations to widespread application an research priority development oral deliverable bait. Previous studies reported successful...
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel are established as primary causative factor devastating lung disease (CF). More recently, cigarette smoke exposure has been shown to be associated with dysfunctional airway epithelial transport, suggesting a role for CFTR pathogenesis of chronic obstructive pulmonary (COPD). Here, identification and characterization high throughput screening hit 6 potentiator mutant human F508del wild-type channels is...
Bovine tuberculosis is an infectious disease of global significance that remains endemic in many countries. Mycobacterium bovis infection cattle characterized by a cell-mediated immune response (CMI) precedes humoral responses, however the timing and trajectories CMI antibody responses determined newer generation assays remain undefined. Here we used defined-antigen interferon-gamma release (IGRA) eleven-antigen multiplex ELISA (Enferplex TB test) alongside traditional tuberculin-based IGRA...
Controlling bovine tuberculosis (bTB) in livestock is often hindered by the presence of a wildlife reservoir, such as Eurasian badger UK and Ireland. Vaccinating badgers against bTB can reduce severity Mycobacterium bovis infection potential onwards transmission to cattle, other species, thus combined with population control might provide additional benefits (and reference models). To evaluate effects co-administration vaccine (BCG) contraceptive (GonaCon), captive were injected...
Further optimization of an initial DP2 receptor antagonist clinical candidate NVP-QAV680 led to the discovery a follow-up molecule 2-(2-methyl-1-(4-(methylsulfonyl)-2-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acetic acid (compound 11, NVP-QAW039, fevipiprant), which exhibits improved potency on human eosinophils and Th2 cells, together with longer residence time, is currently in trials for severe asthma.
Although the liver is primary organ of drug metabolism, lungs also contain drug-metabolizing enzymes and may, therefore, contribute to elimination drugs. In this investigation, Precision-cut Lung Slice (PCLS) technique was standardized with aims characterizing comparing rat human pulmonary metabolizing activity.Due limited availability lung tissue, standardization PCLS method performed tissue. Pulmonary enzymatic activity found vary significantly age strain. The Dynamic Organ Culture (DOC)...
Bovine tuberculosis (bTB) is a global disease of livestock that has damaging economic, animal health and public consequences. Conventional bTB control strategies, based around the testing slaughter cattle infected with bTB, are typically used to help limit or reduce transmission this but in many low- middle-income countries such strategies may often be economically unviable, culturally unacceptable logistically impracticable. The use vaccination protect against could provide potentially more...
Pulmonary arterial hypertension (PAH) is a devastating rare disease, which despite currently available treatments, still represents high unmet medical need. Specific E3 ubiquitin protein ligase 1 (SMURF1) HECT that ubiquitinates key signaling molecules from the TGFβ/BMP pathways, are of great relevance in pathophysiology PAH. Herein, design and synthesis novel potent small-molecule SMURF1 inhibitors described. Lead molecule 38 has demonstrated good oral pharmacokinetics rats significant...
Inhaled amiloride, a blocker of the epithelial sodium channel (ENaC), enhances mucociliary clearance (MCC) in cystic fibrosis (CF) patients. However, dose amiloride is limited by mechanism-based side effect hyperkalaemia resulting from renal ENaC blockade. blockers with reduced potential to induce provide therapeutic strategy improve mucosal hydration and MCC lungs CF The present study describes preclinical profile novel blocker, NVP-QBE170, designed for inhaled delivery, hyperkalaemia.The...
Deuterium isotope effects were evaluated as a strategy to optimize the pharmacokinetics of 7-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-3-(4-methoxy-2-methylphenyl)-2,6-dimethylpyrazolo[5,1-b]oxazole (NVS-CRF38), novel corticotropin-releasing factor receptor 1 (CRF<sub>1</sub>) antagonist. In an attempt suppress O-demethylation NVS-CRF38 without losing activity against CRF<sub>1</sub> receptor, protons at site metabolism replaced with deuterium. For in vitro and vivo studies, intrinsic primary...
Oral vaccination with Mycobacterium bovis Bacille of Calmette and Guerin (BCG) has provided protection against M. to badgers both experimentally in the field. There is also evidence suggesting that persistence live BCG within host important for maintaining TB. Here we investigated capacity badger inductive mucosal sites absorb maintain BCG. The targeted mucosae were oropharyngeal cavity (tonsils sublingual area) small intestine (ileum). We showed significant quantities persisted tissues...
Bovine tuberculosis (TB) in Great Britain adversely affects animal health and welfare is a cause of considerable economic loss. The situation exacerbated by European badgers (Meles meles) acting as wildlife source recurrent Mycobacterium bovis infection to cattle. Vaccination against TB possible means reduce control bovine TB. delivery vaccine oral bait holds the best prospect for vaccinating over wide geographical area. There are practical limitations volume concentration Bacillus Calmette...
To assess the prevalence of Mycobacterium bovis bacilli in faecal samples tuberculous cattle, and to better understand risk environmental dissemination bovine tuberculosis (TB) through spreading manure or slurry.Faecal were collected from 72 naturally infected cattle with visible lesions TB that had reacted tuberculin skin test 12 experimentally M. bovis. These examined by microbial culture PCR presence bacilli. There no positive cultures any reactor animal. A single colony was cultured a...
Bovine tuberculosis (bTB), caused by Mycobacterium bovis infection, is a zoonotic disease in cattle that represents significant ongoing challenge to farming productivity and the livelihoods of livestock farmers UK. Vaccination with BCG could directly target ability M. proliferate within vaccinates, restricting bTB pathogenesis onward transmission, represent step change tools available help control farmed cattle. A Marketing Authorisation (MA) required before vaccine be sold supplied as...
Induction of hepatic amoebiasis with two strains Entamoeba histolytica has been attempted by direct inoculation trophozoites into the livers rats, hamsters, and guinea-pigs, intravenous injection guinea-pigs. A high incidence amoebic abscesses was obtained in hamsters. Rats guinea-pigs were relatively less susceptible. The differed virulence. Serial liver passage increased their virulence for hamster liver, also invasiveness to rat caecum. chemotherapeutic effects chloroquine, emetine, some...