Publications by authors named "Michael Mathieson"
There is currently a public health crisis due to the rise of multidrug-resistant tuberculosis cases, as well as the rise in the number of deaths from tuberculosis. To achieve the United Nations Sustainable Development Goal of ending the tuberculosis epidemic by 2030, new treatments are urgently required. We previously reported the discovery of , a preclinical candidate that acted through inhibition of the lysyl tRNA synthetase (LysRS).
View Article and Find Full Text PDFTuberculosis is a major global cause of both mortality and financial burden mainly in low and middle-income countries. Given the significant and ongoing rise of drug-resistant strains of Mycobacterium tuberculosis within the clinical setting, there is an urgent need for the development of new, safe and effective treatments. Here the development of a drug-like series based on a fused dihydropyrrolidino-pyrimidine scaffold is described.
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- Due to rising drug resistance in tuberculosis patients, there is a critical demand for new drugs targeting novel mechanisms to bypass existing resistance.
- Benzofuran has shown potential as a TB treatment by targeting the thioesterase domain of Pks13, but it poses a risk of inhibiting the hERG cardiac ion channel, leading to heart irregularities.
- Although the research team improved the compound's safety profile, they ultimately halted development due to persistent cardiac concerns, yet the study supports Pks13 as a promising target for new TB drugs and encourages exploring different chemical structures.
Article Synopsis
- There's an urgent need for new oral drugs to combat multi-drug-resistant tuberculosis (TB), particularly those targeting MmpL3.
- Several spirocycle compounds were identified from phenotypic screening, showing potential effectiveness but also presenting cytotoxic risks due to their lipophilic nature and basic amine groups.
- Optimizations led to the discovery of a new zwitterion series with improved properties, but unfortunately, one identified compound lacked efficacy in acute TB infection models despite demonstrating bactericidal activity under certain conditions.
A highly diastereoselective synthesis of trifluoromethylated 1,3-dioxanes is described. The reaction proceeds by an addition/oxa-Michael sequence and works efficiently under mild reaction conditions, with a good substrate scope and acceptable to good yields.
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- The study highlights how native species can quickly adapt to exploit invasive species that have no local predators, boosting their own ecological roles.
- An Australian true bug has evolved longer mouthparts over the last 30-40 years, allowing it to feed on the invasive balloon vine imported from tropical America.
- This genetic adaptation has led to a significant increase in seed predation rates, suggesting that native species can shift their behaviors to help manage invasive threats.
Active learning with support vector machines in the drug discovery process.
J Chem Inf Comput Sci
June 2003
We investigate the following data mining problem from computer-aided drug design: From a large collection of compounds, find those that bind to a target molecule in as few iterations of biochemical testing as possible. In each iteration a comparatively small batch of compounds is screened for binding activity toward this target. We employed the so-called "active learning paradigm" from Machine Learning for selecting the successive batches.
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