A5024033575- Psoriasis: Treatment and Pathogenesis
- Retinoids in leukemia and cellular processes
- Asthma and respiratory diseases
- Advanced Chemical Sensor Technologies
- Estrogen and related hormone effects
- Dermatology and Skin Diseases
- Adipose Tissue and Metabolism
- Analytical Chemistry and Sensors
- Eosinophilic Disorders and Syndromes
- Muscle Physiology and Disorders
- Veterinary Pharmacology and Anesthesia
- Neuroscience of respiration and sleep
- Adipokines, Inflammation, and Metabolic Diseases
- Free Radicals and Antioxidants
- Eosinophilic Esophagitis
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Regulation of Appetite and Obesity
- Biochemical Analysis and Sensing Techniques
- IL-33, ST2, and ILC Pathways
- Cytokine Signaling Pathways and Interactions
AstraZeneca (Sweden)
2014-2025
AstraZeneca (Brazil)
2015
Multiple genetic associations suggest a causative relationship between Th17-related genes coding for proteins, such as IL-17A, IL-23 and STAT3, psoriasis. Further support this link comes from the findings that neutralizing antibodies directed against IL-17RA are efficacious in diseases like psoriasis, psoriatic arthritis ankylosing spondylitis. RORγt is centrally positioned transcription factor driving Th17 polarization cytokine secretion modulation of may thus provide additional benefit to...
Muscle atrophy and cachexia are common comorbidities among patients suffering from cancer, chronic obstructive pulmonary disease, several other diseases. The peptide hormone ghrelin exerts pleiotropic effects including the stimulation of growth secretion subsequent increase insulin-like factor-1 levels, an important mediator muscle repair. Ghrelin also acts on inflammation, appetite, adipogenesis therefore has been considered a promising therapeutic target for catabolic conditions. We...
The further optimization of a recently disclosed series inverse agonists the nuclear receptor RORC2 is described. Investigations into left-hand side compound 1, guided by X-ray crystal structures, led to substitution 4-aryl-thiophenyl residue with hexafluoro-2-phenyl-propan-2-ol moiety. This change resulted in 28, which combined improved drug-like properties good cell potency and significantly lower dose, using an early dose man prediction. Target engagement vivo was demonstrated thymus mice...
Inverse agonists of the nuclear receptor RORC2 have been widely pursued as a potential treatment for variety autoimmune diseases. We discovered novel series isoindoline-based inverse RORC2, derived from our recently disclosed agonist 2. Extensive structure–activity relationship (SAR) studies resulted in AZD0284 (20), which combined potent inhibition IL-17A secretion primary human TH17 cells with excellent metabolic stability and good PK preclinical species. In two vivo studies, compound 20...
<b>Introduction:</b> Classical theory suggests that asthma is driven by a Th2 inflammatory response in the lung. Although this true for many asthmatics it becoming clear others, disease more diverse T cell subsets. <b>Aim:</b> To develop and characterise model of ovalbumin (OVA) LPS induced inflammation may mimic processes involved driving low asthmatics. <b>Methods:</b> Female C57BL/6 mice were sensitized intratracheally with 100µg OVA 1µg 50µl saline at day 0 6. At 13 animals challenged an...
Open chest surgery in rodents requires assisted breathing and the most common approach for ventilation is via an endotracheal tube. Even with well-trained operators intubation technically challenging may lead to prolonged procedures complications. Nose cone a simpler procedure compared has potential improve animal welfare by reducing time associated Rats are obligate nose breathers, therefore replacing air supply from would be advantage more natural way of breathing. Here, we values several...
We have modified the periplasmic Escherichia coli glucose/galactose binding protein (GBP) and labelled with environmentally sensitive fluorophores to further explore its potential as a sensor for evaluation of glucose concentration in airway surface liquid (ASL). identified E149C/A213R GBP N,N’-Dimethyl-N-(iodoacetyl)-N’-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)ethylenediamine (IANBD, emission wavelength maximum 536nm) K d D-glucose 1.02mM fluorescence dynamic range 5.8. This was specific...
Severe eosinophilic asthma remains a clinical burden, potentially due to the multiple mechanisms by which type 2 inflammation can arise. Here we show how epithelial alarmin stimulation of innate lymphoid cells (ILC2s) promote Th2 cell activity and subsequent eosinophil influx lung via dependent upon PI3Kγ δ isoform activity. A PI3Kgamma delta (PI3Kγδ) mRNA signature identified Ubiopred severe asthmatic patient segment with high sputum content Th2/ILC2/alarmin endotype. Evaluation potent PI3K...