A5087639015- NF-κB Signaling Pathways
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Synthesis and Catalytic Reactions
- Cancer therapeutics and mechanisms
- Immune Response and Inflammation
- Chemical Synthesis and Analysis
- Synthesis and bioactivity of alkaloids
- Protein Kinase Regulation and GTPase Signaling
- Microbial Metabolism and Applications
- Axial and Atropisomeric Chirality Synthesis
- Synthesis and biological activity
- Asymmetric Synthesis and Catalysis
- Click Chemistry and Applications
- Tuberculosis Research and Epidemiology
- Chemical synthesis and alkaloids
- Sphingolipid Metabolism and Signaling
- Synthetic Organic Chemistry Methods
- Catalytic C–H Functionalization Methods
- Pharmacological Effects of Natural Compounds
- Chemical Synthesis and Reactions
University of Strathclyde
2011-2024
The University of Sydney
2018
Universitat de Barcelona
2008-2013
The inhibitory-kappaB kinases (IKKs) IKKα and IKKβ play central roles in regulating the non-canonical canonical NF-κB signalling pathways. Whilst proteins that transduce signals of each pathway have been extensively characterised, clear dissection functional IKKα-mediated versus IKKβ-driven remains to be fully elucidated. Progress has relied upon complementary molecular pharmacological tools; however, lack highly potent selective inhibitors limited advances. Herein, we report development an...
IKKβ plays a central role in the canonical NF-kB pathway, which has been extensively characterized. The of IKKα noncanonical and indeed pathway as complex with IKKβ, is less well understood. One major reason for this absence chemical tools designed selective inhibitors over IKKβ. Herein, we report first time series novel, potent, IKKα. We demonstrate effective target engagement selectivity U2OS cells through inhibition IKKα-driven p100 phosphorylation without affecting IKKβ-dependent...
Sphingosine kinase enzymes (SK1 and SK2) catalyze the conversion of sphingosine into 1-phosphate play a key role in lipid signaling cellular responses. Mapping isoform amino acid sequence differences for SK2 onto recently available crystal structures SK1 suggests that subtle structural exist foot lipid-binding "J-channel" SK2, structure which has yet to be defined by biology techniques. We have probed these with ligand series derived from potent SK1-selective inhibitor, PF-543. Here we show...
Society urgently needs new, effective medicines for the treatment of tuberculosis. To kick-start required hit-to-lead campaigns, libraries pharmaceutical companies have recently been evaluated starting points. The GlaxoSmithKline (GSK) library yielded many high-quality hits, and associated data were placed in public domain to stimulate engagement by wider community. One such series, spiro compounds, are described here. compounds explored a combination traditional in-house research open...
The carboline ring system is an important pharmacophore found in a number of biologically targets. Development synthetic routes for the preparation these compounds order to prepare range analogues containing heterocyclic moiety. A manganese dioxide mediated one-pot method starting with activated alcohol and consisting oxidation, Pictet–Spengler cyclisation, oxidative aromatisation, offers convenient process that allows access β-carbolines. This methyl 9 H -pyrido[3,4- b ]indole-1-carboxylate...
The stereochemical outcome of the Lewis acid-mediated glycolate addition titanium enolates from protected N-hydroxyacetyl-4-isopropyl-1,3-thiazolidine-2-thiones to dimethyl and dibenzyl acetals depends on hydroxyl protecting group. Particularly, pivaloyl derivative provides reluctant anti adducts in high yields diastereomeric ratios, which can be isolated further converted enantiomerically pure form β-methoxy or β-benzyloxy α-pivaloyloxy carbonyl fragments a straightforward manner.
Abstract The stereoselective outcome of the title reaction is found to depend on nature O‐protecting group glycolate substrate.