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Success Stories


Publications
French/European academic compound library initiative

Drug Discovery Today

Hibert MF
Drug Discovery Today - vol. 14 723-725 (2009)

Since the year 2000, French academic medicinal chemists took the initiative to collect molecules and natural extracts produced in their labs over the past years to catalyse scientific partnerships with biologists through virtual and experimental screening. This formatted collection was named ‘Chimiothe`que Nationale’ (National Compound Library). After eight years of existence, the outcome in terms […]

Publications
Integrated chemical genomics reveals modifiers of survival in human embryonic stem cells.

Stem cells

Damoiseaux R, Sherman SP, Alva JA, Peterson C, Pyle AD
Stem cells - vol. 27 533-542 (2009)

Understanding how survival is regulated in human embryonic stem cells (hESCs) could improve expansion of stem cells for production of cells for regenerative therapy. There is great variability in comparing the differentiation potential of multiple hESC lines. One reason for this is poor survival upon dissociation, which limits selection of homogeneous populations of cells. Understanding […]

Publications
Limitations in a frataxin knockdown cell model for Friedreich ataxia in a high-throughput drug screen.

BMC neurology

Calmels N, Seznec H, Villa P, Reutenauer L, Hibert M, Haiech J, Rustin P, Koenig M, Puccio H
BMC neurology - vol. 9 46 (2009)

BACKGROUND: Pharmacological high-throughput screening (HTS) represents a powerful strategy for drug discovery in genetic diseases, particularly when the full spectrum of pathological dysfunctions remains unclear, such as in Friedreich ataxia (FRDA). FRDA, the most common recessive ataxia, results from a generalized deficiency of mitochondrial and cytosolic iron-sulfur cluster (ISC) proteins activity, due to a partial […]

Publications
Development and NMR validation of minimal pharmacophore hypotheses for the generation of fragment libraries enriched in heparanase inhibitors

Journal of Computer-Aided Molecular Design

Gozalbes R, Mosulén S, Carbajo RJ, Pineda-Lucena A
Journal of Computer-Aided Molecular Design - vol. 23 555-569 (2009)

A combined strategy based on the development of pharmacophore hypotheses and NMR approaches is reported for the identification of novel inhibitors of heparanase, a key enzyme involved in tumor metastasis through the remodeling of the subepithelial and subendothelial basement membranes, resulting in the dissemination of metastatic cancer cells. Several pharmacophore hypotheses were initially developed from […]

Publications
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 […]

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

PLoS ONE

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 […]

Publications
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 […]

Publications
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 […]

Publications
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 […]

Publications
A high-throughput screening strategy identifies cardiotonic steroids as alternative splicing modulators

Proceedings of the National Academy of Sciences

Stoilov P, Lin C, Damoiseaux R, Nikolic J, Black DL
Proceedings of the National Academy of Sciences - vol. 105 11218-11223 (2008)

10.1073/pnas.0801661105 Alternative splicing has emerged as a promising therapeutic target in a number of human disorders. However, the discovery of compounds that target the splicing reaction has been hindered by the lack of suitable high-throughput screening assays. Conversely, the effects of known drugs on the splicing reaction are mostly unclear and not routinely assessed. We […]