A5101915636- Big Data and Business Intelligence
- Cancer-related Molecular Pathways
- Calcium signaling and nucleotide metabolism
- Estrogen and related hormone effects
- Protein Kinase Regulation and GTPase Signaling
- Crystallization and Solubility Studies
- Hormonal Regulation and Hypertension
- Adenosine and Purinergic Signaling
- X-ray Diffraction in Crystallography
- Cancer therapeutics and mechanisms
- Neonatal Health and Biochemistry
- Adipose Tissue and Metabolism
- Peptidase Inhibition and Analysis
- Synthesis and Characterization of Heterocyclic Compounds
- Microtubule and mitosis dynamics
- Receptor Mechanisms and Signaling
- Synthesis and Biological Evaluation
- Autophagy in Disease and Therapy
- Eicosanoids and Hypertension Pharmacology
- Environmental Monitoring and Data Management
- Conflict of Laws and Jurisdiction
- Protein Structure and Dynamics
- PI3K/AKT/mTOR signaling in cancer
- Carbohydrate Chemistry and Synthesis
- Protein Interaction Studies and Fluorescence Analysis
University of Bath
2012-2023
Stellenbosch University
2007-2020
Legacy Emanuel Medical Center
2020
Harborview Medical Center
2019
University of Washington
2019
University of Oxford
2016
Nottingham Trent University
2012-2015
Bath College
2014
Cyclacel Pharmaceuticals (United Kingdom)
2004-2010
University of Dundee
2010
Quinazolinone-based anticancer agents were designed, decorated with functional groups from a 2-methoxyestradiol-based microtubule disruptor series, incorporating the aryl sulfamate motif of steroid sulfatase (STS) inhibitors. The steroidal AB-ring system was mimicked, favoring conformations an N-2 substituent occupying D-ring space. Evaluation against breast and prostate tumor cell lines identified 7b DU-145 antiproliferative activity (GI50 300 nM). A preliminary structure–activity...
Following the identification through virtual screening of 4-(2,4-dimethyl-thiazol-5-yl)pyrimidin-2-ylamines as moderately potent inhibitors cyclin-dependent kinase-2 (CDK2), a CDK inhibitor analogue program was initiated. The first aims were to optimize potency and evaluate cellular mode action lead candidate molecules. Here synthetic chemistry, structure-guided design approach, structure-activity relationships (SARs) that led discovery 2-anilino-4-(thiazol-5-yl)pyrimidine ATP-antagonistic...
Brain mononuclear phagocyte (perivascular macrophage and microglia, MG) inflammatory neurotoxins play a principal role in the pathogenesis of Parkinson's disease; chief among these are reactive oxygen species (ROS). We posit that aggregated, misfolded oxidized alpha-synuclein (a major constituent Lewy bodies), released or secreted from dying dopaminergic neurons, induces microglial ROS production is regulated by ion channels as such affects disease progression. To address this hypothesis, we...
Through cell-based screening of our kinase-directed compound collection, we discovered that a subset N-phenyl-4-(thiazol-5-yl)pyrimidin-2-amines were potent cytotoxic agents against cancer cell lines, suppressed mitotic histone H3 phosphorylation, and caused aberrant phenotypes. It was subsequently established these compounds in fact inhibitors aurora A B kinases. shown potency selectivity kinase inhibition correlated with the presence substituent at aniline para-position compounds. The...
Poly((N-vinylpyrrolidone)-block-poly(vinyl acetate)) (PVP-b-PVAc) block copolymers of varying molecular weight and hydrophobic lengths were synthesized via controlled radical polymerization investigated as carriers for the solubilization highly riminophenazine compounds. These compounds have recently been shown to exhibit a strong activity against variety cancer types. PVP-b-PVAc self-assembles into polymer vesicles in aqueous media, dialysis method was used load water-insoluble drug...
In 1994, following work from this laboratory, it was reported that estrone-3-O-sulfamate irreversibly inhibits a new potential hormone-dependent cancer target steroid sulfatase (STS). Subsequent drug discovery projects were initiated to develop the core aryl O-sulfamate pharmacophore that, over some 20 years, have led steroidal and nonsteroidal drugs in numerous preclinical clinical trials, with promising results oncology women's health, including endometriosis. Drugs been designed inhibit...
Concurrent inhibition of aromatase and steroid sulfatase (STS) may provide a more effective treatment for hormone-dependent breast cancer than monotherapy against individual enzymes, several dual aromatase-sulfatase inhibitors (DASIs) have been reported. Three with sub-nanomolar potency, better the benchmark agent letrozole, were designed. To further explore DASI concept, new series letrozole-derived sulfamates vorozole-based sulfamate designed biologically evaluated in JEG-3 cells to reveal...
A series of new, all-aromatic, macrocyclic biaryls have been obtained by intramolecular, nickel-promoted coupling bis(4-chlorobenzoylphenoxy)-terminated oligomers, and single-crystal X-ray analysis one such macrocycle reveals extreme distortion the biaryl unit; these highly strained materials undergo rapid ring-opening polymerisation in presence nucleophilic initiators to give high molecular weight polyetherketones.
Abstract Structure–activity relationship studies were conducted on Irosustat (STX64, BN83495), the first steroid sulfatase (STS) inhibitor to enter diverse clinical trials for patients with advanced hormone‐dependent cancer. The size of its aliphatic ring was expanded; sulfamate group N,N‐dimethylated, relocated another position and flanked by an adjacent methoxy group; series quinolin‐2(1 H )‐one quinoline derivatives explored. STS inhibitory activities synthesised compounds assessed in a...
Dual-acting kappa opioid receptor (KOR) agonist and mu (MOR) partial ligands have been put forward as potential treatment agents for cocaine other psychostimulant abuse. Members of the orvinol series are known their high binding affinity to both KOR MOR, but efficacy at individual receptors has not thoroughly evaluated. In this study, it is shown that a predictive model can be derived, with being controlled by length group attached C20 introduction branching into side chain. vivo evaluation...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMULTIDIMENSIONAL LUMINESCENCE MEASUREMENTSIsiah M. Warner, Gabor Patonay, and Mark P. ThomasCite this: Anal. Chem. 1985, 57, 3, 463A–483APublication Date (Print):March 1, 1985Publication History Published online29 May 2012Published inissue 1 March 1985https://pubs.acs.org/doi/10.1021/ac00280a798https://doi.org/10.1021/ac00280a798research-articleACS PublicationsRequest reuse permissionsArticle Views69Altmetric-Citations57LEARN ABOUT THESE...
TRPM2 (transient receptor potential channel, subfamily melastatin, member 2) is a Ca