A5024715369- Protein Degradation and Inhibitors
- Ion Transport and Channel Regulation
- Ubiquitin and proteasome pathways
- Click Chemistry and Applications
- Synthesis and Biological Evaluation
- Mast cells and histamine
- Histone Deacetylase Inhibitors Research
- Cancer Mechanisms and Therapy
- X-ray Diffraction in Crystallography
- Synthesis of Organic Compounds
- Catalytic Cross-Coupling Reactions
- Ion channel regulation and function
- Chronic Myeloid Leukemia Treatments
- Potassium and Related Disorders
- Multiple Myeloma Research and Treatments
- Coordination Chemistry and Organometallics
- Synthesis and Biological Activity
- ATP Synthase and ATPases Research
- Helicobacter pylori-related gastroenterology studies
- Crystallization and Solubility Studies
- Cell Adhesion Molecules Research
- Protease and Inhibitor Mechanisms
- Wnt/β-catenin signaling in development and cancer
- Genetics and Neurodevelopmental Disorders
- Garlic and Onion Studies
GlaxoSmithKline (United Kingdom)
2003-2023
Quantitative BioSciences
2015
Are better drugs just a click away? Drugs that show promise in preclinical models often fail the clinic, part because of limited information on drug localization within cells and across tissues. In proof-of-concept study, Tyler et al. applied chemistry methods to study bromodomain inhibitors. These are cancer alter chromatin structure gene expression. Clickable derivatives localized showed exhibit distinct modes binding at responsive unresponsive genes. mouse leukemia model, click-probes...
Following the discovery of cell penetrant pyridine-4-carboxylate inhibitors KDM4 (JMJD2) and KDM5 (JARID1) families histone lysine demethylases (e.g., 1), further optimization led to identification non-carboxylate derived from pyrido[3,4-d]pyrimidin-4(3H)-one. A number exemplars such as compound 41 possess interesting activity profiles in KDM4C KDM5C biochemical target-specific, cellular mechanistic assays.
Studies investigating the causes of autism spectrum disorder (ASD) point to genetic, as well epigenetic, mechanisms disease. Identification epigenetic processes that contribute ASD development and progression is major importance may lead novel therapeutic strategies. Here, we identify bromodomain extraterminal domain–containing proteins (BETs) regulators genes involved in ASD-like behaviors mice. We found pharmacological suppression BET brain young mice, by novel, highly specific,...
The 2-oxoglutarate-dependent dioxygenase target class comprises around 60 enzymes including several subfamilies with relevance to human disease, such as the prolyl hydroxylases and Jumonji-type lysine demethylases. Current drug discovery approaches are largely based on small molecule inhibitors targeting iron/2-oxoglutarate cofactor binding site. We have devised a chemoproteomics approach combination of unselective active-site ligands tethered beads, enabling affinity capturing 40 different...
Ovarian cancer has a specific unmet clinical need, with persistently poor 5-year survival rate observed in women advanced stage disease warranting continued efforts to develop new treatment options. The amplification of BRD4 significant subset high-grade serous ovarian carcinomas (HGSC) led the development BET inhibitors (BETi) as promising antitumour agents that have subsequently been evaluated phase I/II trials. Here, we describe molecular effects and ex vivo preclinical activities...
3-Arylsulfonyl pyrroles can be readily obtained from 3-Br-TIPS pyrrole via halogen-metal exchange and subsequent sulfonylation. The regioselectivity of the directed ortho-metallation (DOM) reaction in order to functionalise C-2 position depends on nature base (LTMP, n- or s-BuLi) N-substituent (SEM Boc) used. bulk also strongly influences yield Suzuki coupling with 2-iodo-3-arylsulfonyl derivatives.
Abstract For see ChemInform in Full Text.
Abstract Genes encoding subunits of the mammalian SWI/SNF (BAF) ATP-dependent chromatin remodeling complexes are mutated in over 20% human cancer. Specific specific malignancies, highlighting their tissue-specific protective roles; moreover, synthetic lethal screens have uncovered genetic- and lineage-based features that confer dependence on mSWI/SNF subunits. As combinatorial complexity represents a major challenge, identification specialized configurations, subunit-specific functions,...