A5065387940- Receptor Mechanisms and Signaling
- Diabetes Treatment and Management
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Cellular Mechanics and Interactions
- Biochemical and Molecular Research
- Cell Adhesion Molecules Research
- Synthesis and Catalytic Reactions
- Cardiomyopathy and Myosin Studies
- Organic Chemistry Cycloaddition Reactions
- Helicobacter pylori-related gastroenterology studies
- Microtubule and mitosis dynamics
- Steroid Chemistry and Biochemistry
- Gastroesophageal reflux and treatments
- Epigenetics and DNA Methylation
- Ion Transport and Channel Regulation
- Metabolism, Diabetes, and Cancer
Cancer Research UK
2019
Cancer Research Horizons
2009
GlaxoSmithKline (United Kingdom)
2009
A weak screening hit with suboptimal physicochemical properties was optimized against PFKFB3 kinase using critical structure-guided insights. The resulting compounds demonstrated high selectivity over related PFKFB isoforms and modulation of the target in a cellular context. selected example exposure animals following oral dosing. Examples from this series may serve as useful probes to understand emerging biology metabolic target.
// Katerina Mardilovich 1 , Mark Baugh Diane Crighton Dominika Kowalczyk Mads Gabrielsen June Munro Daniel R. Croft Filipe Lourenco James Gabriella Kalna Lynn McGarry Oliver Rath Emma Shanks Mathew J. Garnett 2 Ultan McDermott Joanna Brookfield 3 Charles Tim Hammonds 4 and Michael F. Olson Cancer Research UK Beatson Institute, Garscube Estate, Glasgow, Genome Project, Wellcome Trust Sanger Hinxton, Technology Discovery Laboratories, Jonas Webb Building, Babraham Campus, Cambridge, London...
Tumors have evolved a variety of methods to reprogram conventional metabolic pathways favor their own nutritional needs, including glutaminolysis, the first step which is hydrolysis glutamine glutamate by amidohydrolase glutaminase 1 (GLS1). A GLS1 inhibitor could potentially target certain cancers blocking tumor cell's ability produce glutamine-derived nutrients. Starting from known bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide, we describe medicinal chemistry evolution...
As part of a program to develop small molecule inhibitor LIMK, series aminothiazole inhibitors were discovered by high throughput screening. Scaffold hopping and subsequent SAR directed development led low nanomolar LIMK1 LIMK2 that also inhibited the direct biomarker p-cofilin in cells invasion MDA MB-231-luc matrigel inverse assay.
Abstract Glutamine is an essential nutrient for cancer cells and used to support cell growth. converted glutamate by the enzyme glutaminase, which then into alpha-ketoglutarate, a metabolic intermediate within TCA cycle serves as precursor biosynthesis of ATP, NADPH, fatty acids, glutathione, nucleic acids amino acids. As such, we regarded glutaminolysis key pathway therapeutic intervention. At outset project there were several reported inhibitors glutaminase known in literature; however,...
Abstract The invasive potential of carcinomas greatly contributes to their ability metastasize, a process which is estimated cause 90% all human cancer deaths. LIM kinase (LIMK) family Ser/Thr kinases sit at hub signaling pathways downstream the Rho GTPases. Functionally, LIMK directly involved in regulating activity cofilin, proteins modulate cell movement through reorganization actin cytoskeleton network. up-regulated number lines and metastatic breast prostate tumors, whilst an increase...