A5002912000- Natural Compound Pharmacology Studies
- Peptidase Inhibition and Analysis
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Bioactive natural compounds
- Synthesis of Organic Compounds
- Multiple Myeloma Research and Treatments
- Synthetic Organic Chemistry Methods
- Chemical Synthesis and Analysis
- Protein Degradation and Inhibitors
- Microbial Natural Products and Biosynthesis
- Natural product bioactivities and synthesis
- Biochemical and Structural Characterization
- Phytochemistry and Biological Activities
- Biochemical and Molecular Research
- Carbohydrate Chemistry and Synthesis
- Antifungal resistance and susceptibility
- Enzyme Structure and Function
- Renin-Angiotensin System Studies
- Systemic Lupus Erythematosus Research
- Asymmetric Synthesis and Catalysis
- Mast cells and histamine
- Ubiquitin and proteasome pathways
- Cancer Genomics and Diagnostics
- Advancements in Transdermal Drug Delivery
Laboratoire d'Informatique en Images et Systèmes d'Information
2016-2024
University of Birmingham
2012
University of Nottingham
2006-2007
GlaxoSmithKline (United Kingdom)
2007
Laboratoire de Chimie Organique
2003-2005
Centre National de la Recherche Scientifique
2003-2005
Université de Haute-Alsace
2003-2005
École nationale supérieure de chimie de Mulhouse
2003-2005
ATAD2 (ANCCA) is an epigenetic regulator and transcriptional cofactor, whose overexpression has been linked to the progress of various cancer types. Here, we report a DNA-encoded library screen leading discovery BAY-850, potent isoform selective inhibitor that specifically induces bromodomain dimerization prevents interactions with acetylated histones in vitro, as well chromatin cells. These features qualify BAY-850 chemical probe explore biology.
The synthesis of polyprenylated phloroglucinol natural products, including clusianone, nemorosone, and garsubellin A, was pursued by a strategy involving construction core bicyclo[3.3.1]nonanetrione structure subsequent elaboration via organolithium intermediates. Appropriate bridged structures were obtained through the cyclization suitably substituted cyclohexanone enol ether or silane with malonyl dichloride. Additional substituents then introduced means regioselective lithiation...
A concise synthesis of the polyprenylated acylphloroglucinol natural product, clusianone, in racemic form, is described. An Effenburger cyclization generated a core bicyclo[3.3.1]nonane-trione structure, which was then elaborated by means regioselective lithiation reactions.
A chiral base kinetic resolution of an advanced bicyclic intermediate enabled access to the polyprenylated phloroglucinol natural product (+)-clusianone in enantiomerically pure form. X-ray structure determination another obtained by same method then allowed absolute stereochemistry be assigned.
PIF1 is a conserved helicase and G4 DNA binding unwinding enzyme, with roles in genome stability. Human (hPIF1) poorly understood, but its functions can become critical for tumour cell survival during oncogene-driven replication stress. Here we report the discovery, via an X-ray crystallographic fragment screen (XChem), of hPIF1 inhibitors. A structure was obtained 4-phenylthiazol-2-amine bound pocket between domains 2A 2B, additional contacts to Valine 258 from domain 1A. The compound makes...
The preparation of a series new fumagillin-derived MetAP-2 inhibitors is described. synthetic approach was designed so as to permit modification the fumagillin backbone at sites inaccessible through semisynthesis or previously existing total syntheses. An Evans aldolization and ring-closing metathesis allowed pivotal intermediate which could then be functionalized in various ways using already established newly developed methodologies.
Bridgehead lithiations have successfully been carried out on substrates derived from catechinic acid, which possess the core bicyclo[3.3.1]nonane-1,3,5-trione structure present in garsubellin A. Using an external quench method, various electrophiles incorporated at C-5 bridgehead position a one-step process that appears to be sensitive substitution pattern bicyclic system. Regioselective lithiation C-3 sp2 centre was achieved by changing base used LDA LTMP. Following introduction of prenyl...
[reaction: see text] Enantioselective deprotonation of 4-substituted cyclohexanones and highly stereoselective conjugate addition higher order mixed cuprates were the key steps in a concise synthesis fumagalone-related molecules. The origin (low) biological activity new compounds as compared to fumagalone is briefly discussed.
The use of an interleukin β antibody is currently being investigated in the clinic for treatment acne, a dermatological disorder affecting 650M persons globally. Inhibiting protease responsible cleavage inactive pro-IL1β into active IL-1β, caspase-1, could be alternative small molecule approach. This report describes discovery uracil 20, potent (38 nM THP1 cells assay) caspase-1 inhibitor topical inflammatory acne. series was designed according to published pharmacophore model involving...
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by overactive immune response, particularly involving excessive production of type I interferons. This overproduction driven the phosphorylation IRF7, a crucial factor in interferon gene activation. Current treatments for SLE are often not very effective and can have serious side effects.
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Clusianone, a polyprenylated acylphloroglucinol, shows promise for cancer prevention and the treatment of HIV. This synthesis employs Effenberger protocol (F. co-workers Chem. Ber. 1984, 117, 3280-3296) to access fused bicyclic core regioselective lithiation-alkylation strategies append remaining functionality. For closely related clusianone, see: P. Nuhant et al. Org. Lett. 2007, 9, 287-289.
Abstract ATAD2 (ATPase family AAA-domain containing protein 2, also called ANCCA) is an epigenetic regulator that binds to chromatin through its bromodomain (BD), a motif specialized for acetyl-lysine recognition. directly associates with multiple transcription factors such as ERα, AR, E2F, and Myc; hence, has been proposed act co-factor oncogenic factors. Furthermore, we have recently reported novel role during DNA replication, uncovering interactions between histone acetylation marks on...