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5 results on '"Katherine S. England"'

1. Recent Progress in Histone Demethylase Inhibitors

Author

Akane Kawamura, Katherine S. England, Richard J. Hopkinson, Tom E. McAllister, Paul Brennan, and Christopher J. Schofield

Subjects
Models, Molecular, 0301 basic medicine, Molecular Sequence Data, Patent literature, Computational biology, Bioinformatics, complex mixtures, Small Molecule Libraries, 03 medical and health sciences, Drug Discovery, Animals, Humans, Amino Acid Sequence, Enzyme Inhibitors, Histone Demethylases, biology, Chemistry, Drug discovery, 3. Good health, 030104 developmental biology, Histone, biology.protein, bacteria, Molecular Medicine, Demethylase, Peptides
Abstract

There is increasing interest in targeting histone N-methyl-lysine demethylases (KDMs) with small molecules both for the generation of probes for target exploration and for therapeutic purposes. Here we update on previous reviews on the inhibition of the lysine-specific demethylases (LSDs or KDM1s) and JmjC families of N-methyl-lysine demethylases (JmjC KDMs, KDM2-7), focusing on the academic and patent literature from 2014 to date. We also highlight recent biochemical, biological, and structural studies which are relevant to KDM inhibitor development.

Published
2016
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2. Design and Synthesis of a Pan-Janus Kinase Inhibitor Clinical Candidate (PF-06263276) Suitable for Inhaled and Topical Delivery for the Treatment of Inflammatory Diseases of the Lungs and Skin

Author

Iain Kilty, Yogesh A. Sabnis, Paul Morgan, Jill Chrencik, Florian Wakenhut, John Murphy, Jotham Wadsworth Coe, Katherine S. England, Takasuke Mukaiyama, David G. Brown, Rhys M. Jones, Thean Yeoh, R. Ian Storer, Gavin A. Whitlock, Christoph Martin Dehnhardt, Peter Jones, and Steve Kortum

Subjects
0301 basic medicine, Lung Diseases, Indazoles, Anti-Inflammatory Agents, Pharmacology, Administration, Cutaneous, Crystallography, X-Ray, Heterocyclic Compounds, 2-Ring, Skin Diseases, 03 medical and health sciences, 0302 clinical medicine, Dogs, Drug Discovery, Administration, Inhalation, Potency, Animals, Humans, Binding site, Phosphorylation, Protein Kinase Inhibitors, Janus kinase inhibitor, Janus Kinases, Mice, Inbred BALB C, Janus kinase 2, Binding Sites, biology, Janus kinase 1, Chemistry, Janus kinase 3, Janus Kinase 3, Janus Kinase 1, Janus Kinase 2, Rats, 030104 developmental biology, Solubility, 030220 oncology & carcinogenesis, QD431, Drug Design, biology.protein, Hepatocytes, Microsomes, Liver, Molecular Medicine, Janus kinase
Abstract

By use of a structure-based computational method for identification of structurally novel Janus kinase (JAK) inhibitors predicted to bind beyond the ATP binding site, a potent series of indazoles was identified as selective pan-JAK inhibitors with a type 1.5 binding mode. Optimization of the series for potency and increased duration of action commensurate with inhaled or topical delivery resulted in potent pan-JAK inhibitor 2 (PF-06263276), which was advanced into clinical studies.

Published
2016

3. Acidic triazoles as soluble guanylate cyclase stimulators

Author

Michael A. Tones, Paul A. Bradley, Graham L. Smith, Lee R. Roberts, Geoff E. Gymer, Katherine S. England, Fox David Nathan Abraham, Steven E. Heasley, Michelle Schmidt, Mark E. Bunnage, Yvette M. Fobian, Jerome Molette, David Fairman, and Dack Kevin Neil

Subjects
chemistry.chemical_classification, GUCY1B3, Organic Chemistry, Clinical Biochemistry, GUCY1A3, Triazole, Guanylate Cyclase Stimulators, Enzyme Activators, Receptors, Cytoplasmic and Nuclear, Pharmaceutical Science, Triazoles, Biochemistry, chemistry.chemical_compound, Soluble Guanylyl Cyclase, Enzyme, chemistry, Guanylate Cyclase, Drug Discovery, Molecular Medicine, Organic chemistry, Molecule, Acids, Molecular Biology
Abstract

A series of acidic triazoles with activity as soluble guanylate cyclase stimulators is described. Incorporation of the CF3 triazole improved the overall physicochemical and drug-like properties of the molecule and is exemplified by compound 25.

Published
2011
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4. An improved synthesis of a novel α1A partial agonist including a new two-step synthesis of 4-fluoropyrazole

Author

Rachel Osborne, Katherine S. England, Lee R. Roberts, and Helen J. Mason

Subjects
Chemistry, Organic Chemistry, Drug Discovery, Two step, Biochemistry, Combinatorial chemistry, Partial agonist
Abstract

This Letter outlines a new two-step process for the synthesis of 4-fluoropyrazole and its application in an improved synthesis of 4-fluoro-1-[5-fluoro-1-(1H-imidazol-2-yl)-indan-4-ylmethyl]-1H-pyrazole. The original synthesis of 4-fluoro-1-[5-fluoro-1-(1H-imidazol-2-yl)-indan-4-ylmethyl]-1H-pyrazole is also described.

Published
2010
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5. Optimisation of a triazolopyridine based histone demethylase inhibitor yields a potent and selective KDM2A (FBXL11) inhibitor

Author

K.H. Che, Katherine S. England, Akane Kawamura, Christopher J. Schofield, G Scozzafava, N.A. Burgess-Brown, F. von Delft, M. Daniel, A. Szykowska, S.S. Ng, Anthony Tumber, T. Krojer, and Paul Brennan

Subjects
Stereochemistry, Lysine, Triazole, Pharmaceutical Science, KDM2A, 01 natural sciences, Biochemistry, Article, 03 medical and health sciences, chemistry.chemical_compound, Oxidoreductase, Drug Discovery, 030304 developmental biology, Pharmacology, chemistry.chemical_classification, 0303 health sciences, biology, 010405 organic chemistry, Organic Chemistry, Active site, 3. Good health, 0104 chemical sciences, Histone, chemistry, biology.protein, Molecular Medicine, Demethylase, Triazolopyridine
Abstract

A potent inhibitor of the JmjC histone lysine demethylase KDM2A (compound 35, pIC50 7.2) with excellent selectivity over representatives from other KDM subfamilies has been developed; the discovery that a triazolopyridine compound binds to the active site of JmjC KDMs was followed by optimisation of the triazole substituent for KDM2A inhibition and selectivity. This journal is

Published
2014

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