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 […]

Establishment of human papillomavirus infection requires cell cycle progression

PLoS Pathogens

Pyeon D, Pearce SM, Lank SM, Ahlquist P, Lambert PF
PLoS Pathogens - vol. 5 (2009)

Human papillomaviruses (HPVs) are DNA viruses associated with major human cancers. As such there is a strong interest in developing new means, such as vaccines and microbicides, to prevent HPV infections. Developing the latter requires a better understanding of the infectious life cycle of HPVs. The HPV infectious life cycle is closely linked to the […]

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 […]

Cardiac glycosides induce cell death in human cells by inhibiting general protein synthesis


Perne A, Muellner MK, Steinrueck M, Craig-Mueller N, Mayerhofer J, Schwarzinger I, Sloane M, Uras IZ, Hoermann G, Nijman SMB, Mayerhofer M
PLoS ONE - vol. 4 (2009)

BACKGROUND: Cardiac glycosides are Na(+)/K(+)-pump inhibitors widely used to treat heart failure. They are also highly cytotoxic, and studies have suggested specific anti-tumor activity leading to current clinical trials in cancer patients. However, a definitive demonstration of this putative anti-cancer activity and the underlying molecular mechanism has remained elusive.nnMETHODOLOGY/PRINCIPAL FINDINGS: Using an unbiased transcriptomics approach, […]

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 […]

A Chemical Genetic Screen for mTOR Pathway Inhibitors Based on 4E-BP-Dependent Nuclear Accumulation of eIF4E

Chemistry and Biology

Livingstone M, Larsson O, Sukarieh R, Pelletier J, Sonenberg N
Chemistry and Biology - vol. 16 1240-1249 (2009)

The signal transduction pathway wherein mTOR regulates cellular growth and proliferation is an active target for drug discovery. The search for new mTOR inhibitors has recently yielded a handful of promising compounds that hold therapeutic potential. This search has been limited by the lack of??a high-throughput assay to monitor the phosphorylation of a direct rapamycin-sensitive […]

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 […]

Combining chemical genomics screens in yeast to reveal spectrum of effects of chemical inhibition of sphingolipid biosynthesis.

BMC microbiology

Kemmer D, McHardy LM, Hoon S, Rebérioux D, Giaever G, Nislow C, Roskelley CD, Roberge M
BMC microbiology - vol. 9 9 (2009)

BACKGROUND: Single genome-wide screens for the effect of altered gene dosage on drug sensitivity in the model organism Saccharomyces cerevisiae provide only a partial picture of the mechanism of action of a drug.nnRESULTS: Using the example of the tumor cell invasion inhibitor dihydromotuporamine C, we show that a more complete picture of drug action can […]

Incidence and specificity of drug-induced trafficking inhibition of cardiac ion channels

Journal of Pharmacological and Toxicological Methods

Wible BA
Journal of Pharmacological and Toxicological Methods - vol. 60 223 (2009)

A high throughput assay to identify small molecule modulators of prostatic acid phosphatase.

Current chemical genomics

Larsen RS, Zylka MJ, Scott JE
Current chemical genomics - vol. 3 42-9 (2009)

Prostatic acid phosphatase (PAP) is expressed in nociceptive neurons and functions as an ectonucleotidase. Injection of the secretory isoform of PAP has potent antinociceptive effects in mouse models of chronic pain. These data suggested that a small molecule activator of PAP may have utility as a novel therapeutic for chronic pain, while inhibitors could be […]