A small molecule that directs differentiation of human ESCs into the pancreatic lineage.

Nature chemical biology

Chen S, Borowiak M, Fox JL, Maehr R, Osafune K, Davidow L, Lam K, Peng LF, Schreiber SL, Rubin LL, Melton D
Nature chemical biology - vol. 5 258-265 (2009)

Stepwise differentiation from embryonic stem cells (ESCs) to functional insulin-secreting beta cells will identify key steps in beta-cell development and may yet prove useful for transplantation therapy for diabetics. An essential step in this schema is the generation of pancreatic progenitors–cells that express Pdx1 and produce all the cell types of the pancreas. High-content chemical […]

High-throughput screening for daunorubicin-mediated drug resistance identifies mometasone furoate as a novel ABCB1-reversal agent.

Journal of biomolecular screening

Winter SS, Lovato DM, Khawaja HM, Edwards BS, Steele ID, Young SM, Oprea TI, Sklar LA, Larson RS
Journal of biomolecular screening - vol. 13 185-93 (2008)

The overexpression of P-glycoprotein, encoded by the ATP Binding Cassette B1 (ABCB1) gene, contributes to multidrug resistance (MDR) and is considered one of the major obstacles to successful cancer chemotherapy. The authors previously developed a T-lineage acute lymphoblastic leukemia (T-ALL) cell line that overexpresses ABCB1 and exhibits MDR to daunorubicin (DNR), prednisolone, and vincristine. Using […]

High-Throughput Screening Assay for the Identification of Compounds Regulating Self-Renewal and Differentiation in Human Embryonic Stem Cells

Cell Stem Cell

Desbordes SC, Placantonakis DG, Ciro A, Socci ND, Lee G, Djaballah H, Studer L
Cell Stem Cell - vol. 2 602-612 (2008)

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 […]

Antihypertensive drug guanabenz is active in vivo against both yeast and mammalian prions


Tribouillard-Tanvier D, Béringue V, Desban N, Gug F, Bach S, Voisset C, Galons H, Laude H, Vilette D, Blondel M
PLoS ONE - vol. 3 (2008)

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 […]

Tiratricol neutralizes bacterial endotoxins and reduces lipopolysaccharide-induced TNF-α production in the cell

Chemical Biology and Drug Design

Cascales L, Mas-Moruno C, Tamborero S, Aceña JL, Sanz-Cervera JF, Fustero S, Cruz LJ, Mora P, Albericio F, Pérez-Payá E
Chemical Biology and Drug Design - vol. 72 320-328 (2008)

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 […]

Quantitative assessment of hit detection and confirmation in single and duplicate high-throughput screenings.

Journal of biomolecular screening

Wu Z, Liu D, Sui Y
Journal of biomolecular screening - vol. 13 159-67 (2008)

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 […]

Known Bioactive Small Molecules Probe the Function of a Widely Conserved but Enigmatic Bacterial ATPase, YjeE

Chemistry and Biology

Mangat CS, Brown ED
Chemistry and Biology - vol. 15 1287-1295 (2008)

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 […]

Application of high-throughput isothermal denaturation to assess protein stability and screen for ligands.

Journal of biomolecular screening

Senisterra GA, Soo Hong B, Park H, Vedadi M
Journal of biomolecular screening - vol. 13 337-42 (2008)

Many diseases in humans are caused by mutations that decrease the stability of specific proteins or increase their susceptibility to aggregation. Consequently, the availability of high-throughput methods for assessing protein stability and aggregation properties under physiological conditions (e.g., 37 degrees C) is necessary to analyze physicochemical properties under conditions that are closer to in vivo […]

Identification of Small Molecule Inhibitors of β–Amyloid Cytotoxicity through a Cell-based High-Throughput Screening Platform

Journal of Biomolecular Screening

Seyb KI, Schuman ER, Ni J, Huang M, Michaelis ML, Glicksman MA
Journal of Biomolecular Screening - vol. 13 870-878 (2008)

Fluorescence spectroscopic profiling of compound libraries

Journal of Medicinal Chemistry

Simeonov A, Jadhav A, Thomas CJ, Wang Y, Huang R, Southall NT, Shinn P, Smith J, Austin CP, Auld DS, Inglese J
Journal of Medicinal Chemistry - vol. 51 2363-2371 (2008)

Chromo/fluorophoric properties often accompany the heterocyclic scaffolds and impurities that comprise libraries used for high-throughput screening (HTS). These properties affect assay outputs obtained with optical detection, thus complicating analysis and leading to false positives and negatives. Here, we report the fluorescence profile of more than 70,000 samples across spectral regions commonly utilized in HTS. The […]