A5070390298- Psoriasis: Treatment and Pathogenesis
- Immunodeficiency and Autoimmune Disorders
- Eicosanoids and Hypertension Pharmacology
- Asthma and respiratory diseases
- Free Radicals and Antioxidants
- Inflammatory mediators and NSAID effects
- Dermatology and Skin Diseases
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
- NF-κB Signaling Pathways
- Autoimmune Bullous Skin Diseases
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Pharmacogenetics and Drug Metabolism
- Antibiotic Resistance in Bacteria
- Alcohol Consumption and Health Effects
- T-cell and B-cell Immunology
- Microbial Natural Products and Biosynthesis
- Diet, Metabolism, and Disease
- IL-33, ST2, and ILC Pathways
- Cancer therapeutics and mechanisms
Constellation Pharmaceuticals (United States)
2018
GlaxoSmithKline (United Kingdom)
2015
GlaxoSmithKline (United States)
2014-2015
Temper (United States)
2014
Pfizer (United States)
2010-2011
Enhancer of zeste homolog 2–mediated (EZH2-mediated) epigenetic regulation T cell differentiation and Treg function has been described previously; however, the role EZH2 in cell–mediated antitumor immunity, especially context immune checkpoint therapy, is not understood. Here, we showed that genetic depletion Tregs (FoxP3creEZH2fl/fl mice) leads to robust immunity. In addition, pharmacological inhibition human cells using CPI-1205 elicited phenotypic functional alterations enhanced cytotoxic...
IL-17-producing CD4(+)Th17 cells, CD8(+)Tc17 and γδ T cells play critical roles in the pathogenesis of autoimmune psoriasis. RORγt is required for differentiation Th17 expression IL-17. In this article, we describe a novel, potent, selective inverse agonist (TMP778), its inactive diastereomer (TMP776). This chemistry, first time to our knowledge, provides unique powerful set tools probe RORγt-dependent functions. TMP778, but not TMP776, blocked human Tc17 cell also acutely modulated IL-17A...
QPT-1 was discovered in a compound library by high-throughput screening and triage for substances with whole-cell antibacterial activity. This totally synthetic is an unusual barbituric acid derivative whose activity resides the (-)-enantiomer. had against broad spectrum of pathogenic, antibiotic-resistant bacteria, nontoxic to eukaryotic cells, showed oral efficacy murine infection model, all before any medicinal chemistry optimization. Biochemical genetic characterization that targets beta...
Structure-based virtual screening was applied to design combinatorial libraries discover novel and potent soluble epoxide hydrolase (sEH) inhibitors. X-ray crystal structures revealed unique interactions for a benzoxazole template in addition the conserved hydrogen bonds with catalytic machinery of sEH. By exploitation favorable binding elements, two iterations library based on amide coupling were employed, guided principally by docking results enumerated products. Biological demonstrated as...
Summary The orphan nuclear receptor, retinoic acid receptor‐related receptor γ t ( ROR t), is required for the development and pathogenic function of interleukin‐17A‐secreting CD 4 + T helper type 17 (Th17) cells. Whereas small molecule antagonists impair Th17 cell attenuate autoimmune inflammation in vivo , broader effects these inhibitors on t‐dependent gene expression has yet to be characterized. We show that inverse agonist TMP 778 acts potently selectively block mouse differentiation...
Abstract IL-17-producing Th17 cells, Tc17 cells and γδ T play critical roles in the pathogenesis of autoimmune psoriasis. RORγt is required for differentiation expression IL-17. Here we describe a novel, potent, selective inverse agonist (TMP778), its inactive diastereomer (TMP776). This chemistry, first time, provides unique powerful set tools to probe RORγt-dependent functions. TMP778, but not TMP776, blocked human cell also acutely modulated Th17-signature gene expression. In addition,...