Publications

High-throughput screening (HTS) of chemical libraries has become a critical tool in basic biology and drug discovery. However, its implementation and the adaptation of high-content assays to human embryonic stem cells (hESCs) have been hampered by multiple technical challenges. Here we present a strategy to adapt hESCs to HTS conditions, resulting in an assay suitable […]

BACKGROUND: Prion-based diseases are incurable transmissible neurodegenerative disorders affecting animals and humans.nnMETHODOLOGY/PRINCIPAL FINDINGS: Here we report the discovery of the in vivo antiprion activity of Guanabenz (GA), an agonist of alpha2-adrenergic receptors routinely used in human medicine as an antihypertensive drug. We isolated GA in a screen for drugs active in vivo against two different […]

The screening of a commercially available library of compounds has proved a successful strategy for the identification of a lead compound in a drug discovery programme. Here, we analysed 880 off-patent drugs, which initially comprised the Prestwick Chemical library, as sources of bacterial endotoxin neutralizers. We identified 3,3′,5-triiodo-thyroacetic acid (tiratricol) as a non-antibacterial compound that […]

The process of identifying active targets (hits) in high-throughput screening (HTS) usually involves 2 steps: first, removing or adjusting for systematic variation in the measurement process so that extreme values represent strong biological activity instead of systematic biases such as plate effect or edge effect and, second, choosing a meaningful cutoff on the calculated statistic […]

Escherichia coli YjeE is a broadly conserved bacterial ATPase of unknown function that has been widely characterized as essential. Here, the transcriptional regulation of the promoter of yjeE (P yjeE) was probed using a luciferase reporter and 172 antibiotics of diverse mechanisms. Norfloxacin and other fluorquinolones were found to be the most potent activator of […]

The aim of this study was to investigate the permeation properties of 20 permanently positive charged molecules in the parallel artificial membrane permeability assay (PAMPA). Eight of them were derivatives of the N-alkyl-isoquinolinium salt and 12 were congeners of the dye rhodamine 110. Five out of 12 molecules from the rhodamine 110 series have one […]

High-throughput screening (HTS) is the primary technique for new lead identification in drug discovery and chemical biology. Unfortunately, it is susceptible to false-positive hits. One common mechanism for such false-positives is the congregation of organic molecules into colloidal aggregates, which nonspecifically inhibit enzymes. To both evaluate the feasibility of large-scale identification of aggregate-based inhibition and […]

High throughput screening (HTS) data is often noisy, containing both false positives and negatives. Thus, careful triaging and prioritization of the primary hit list can save time and money by identifying potential false positives before incurring the expense of followup. Of particular concern are cell-based reporter gene assays (RGAs) where the number of hits may […]

There is an urgent need for the development of new antifungal agents. A facile in vivo model that evaluates libraries of chemical compounds could solve some of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida species, are ingested by Caenorhabditis elegans and establish a persistent lethal […]