A5040689242- Melanoma and MAPK Pathways
- Tryptophan and brain disorders
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Stress Responses and Cortisol
- Skin and Cellular Biology Research
- Bipolar Disorder and Treatment
- Synthesis of Tetrazole Derivatives
- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Synthesis and biological activity
- Cancer Mechanisms and Therapy
- Computational Drug Discovery Methods
- Contact Dermatitis and Allergies
- Chronic Lymphocytic Leukemia Research
- Immune Cell Function and Interaction
- Cellular Mechanics and Interactions
- Mast cells and histamine
- Galectins and Cancer Biology
- Immunotherapy and Immune Responses
- Metal-Catalyzed Oxygenation Mechanisms
- Histone Deacetylase Inhibitors Research
- Gut microbiota and health
- Peptidase Inhibition and Analysis
- Phytochemical compounds biological activities
- Proteins in Food Systems
Age UK
2021-2024
GlaxoSmithKline (United Kingdom)
2007-2021
GlaxoSmithKline (India)
2019
GlaxoSmithKline (France)
2014
Molecular Discovery (United Kingdom)
2014
GlaxoSmithKline (United States)
2006
Research Triangle Park Foundation
2006
Through their function as epigenetic readers of the histone code, BET family bromodomain-containing proteins regulate expression multiple genes therapeutic relevance, including those involved in tumor cell growth and inflammation. bromodomain inhibitors have profound antiproliferative anti-inflammatory effects which translate into efficacy oncology inflammation models, first compounds now progressed clinical trials. The exciting biology BETs has led to great interest discovery novel...
Abstract Six soils from a chronosequence were chosen to test the effects of magnetite on using free Fe estimate relative ages soils. The acid‐ammonium oxalate and dithionite‐citrate‐bicarbonate methods used extract samples. Iron values these two extractions compared for samples which was removed, not fraction itself. Visual examinations also made untreated treated grains. solution releases in proportion amount soil. dithionite does release magnetite, but hematite coatings replacements Large...
The functions of the bromodomain and extra terminal (BET) family proteins have been implicated in a wide range diseases, particularly oncology immuno-inflammatory areas, several inhibitors are under investigation clinic. To mitigate risk attrition these compounds due to structurally related toxicity findings, additional molecules from distinct chemical series were required. Here we describe structure- property-based optimization vivo tool molecule I-BET151 toward I-BET282E, with properties...
Abstract Kynurenine-3-monooxygenase (KMO) is a key FAD-dependent enzyme of tryptophan metabolism. In animal models, KMO inhibition has shown benefit in neurodegenerative diseases such as Huntington’s and Alzheimer’s. Most recently it been identified target for acute pancreatitis multiple organ dysfunction syndrome (AP-MODS); devastating inflammatory condition with mortality rate excess 20%. Here we report dissect the molecular mechanism action three classes inhibitors differentiated binding...
p38α MAP kinase is a key anti-inflammatory target for rheumatoid arthritis, influencing biosynthesis of pro-inflammatory cytokines TNFα and IL-1β at translational transcriptional level. In this paper, we describe how have optimized series novel p38α/β inhibitors using crystal structures our bound to p38α, classical medicinal chemistry, modeling virtual libraries derive molecule suitable progression into clinical development.
Recently, we reported a novel role for KMO in the pathogenesis of acute pancreatitis (AP). A number inhibitors kynurenine 3-monooxygenase (KMO) have previously been described as potential treatments neurodegenerative conditions and particularly Huntington's disease. However, to date insufficient aqueous solubility relative their cellular potency be compatible with intravenous (iv) dosing route required AP. We identified optimized series high affinity favorable physicochemical properties. The...
B-cell lymphoma 6 (BCL6) is a zinc finger transcriptional repressor possessing BTB–POZ (BR-C, ttk, and bab for BTB; pox virus POZ) domain, which required homodimerization association with corepressors. BCL6 has multiple roles in normal immunity, autoimmunity, some types of lymphoma. Mice bearing disrupted loci demonstrate suppressed high-affinity antibody responses to T-dependent antigens. The corepressor binding groove the domain potential target small compound-mediated therapy. Several...
The scaling‐up of a method for the production an enzymic hydrolsate casein is descrived; minor modifications laboratory procedure were required. spray‐dried product relatively free bitterness often associated with proteins subjected to treatment. bacteriological load raw materials, intermediate stages, and final was monitored. hydrolysed in quantity providing opportunity investigate dietary potential pre‐digested protein patients suffering from digestive disorders as result pancreatic malfunction.
The inhibition of kallikrein 5 (KLK5) has been identified as a potential strategy for treatment the genetic skin disorder Netherton syndrome, in which loss-of-function mutations SPINK5 gene lead to down-regulation endogenous inhibitor LEKTI-1 and profound skin-barrier defects with severe allergic manifestations. To aid development medicine this target, an X-ray crystallographic system was developed facilitate fragment-guided chemistry knowledge-based drug-discovery approaches. Here,...
Endoplasmic reticulum aminopeptidase 1 (ERAP1) cleaves the N-terminal amino acids of peptides, which can then bind onto major histocompatibility class I (MHC-I) molecules for presentation cell surface, driving activation adaptive immune responses. In cancer, overtrimming mature antigenic peptides reduce cytotoxic T-cell responses, and ERAP1 generate self-antigenic contribute to autoimmune cellular Therefore, modulation activity has potential therapeutic indications cancer immunotherapy in...