Archives des Publications - Page 27 sur 44 - Prestwick Chemical Libraries

Publications

Caenorhabditis elegans as a chemical screening tool for the study of neuromuscular disorders. Manual and semi-automated methods

Methods

Giacomotto J, S??galat L, Carre-Pierrat M, Gieseler K
Methods - vol. 56 103-113 (2012)

We previously reported the use of the cheap and fast-growing nematode Caenorhabditis elegans to search for molecules, which reduce muscle degeneration in a model for Duchenne Muscular Dystrophy (DMD). We showed that Prednisone, a steroid that is generally prescribed as a palliative treatment to DMD patients, also reduced muscle degeneration in the C. elegans DMD […]

Publications

The monoamine oxidase A inhibitor clorgyline is a broad-spectrum inhibitor of fungal ABC and MFS transporter efflux pump activities which reverses the azole resistance of Candida albicans and Candida glabrata clinical isolates

Antimicrobial Agents and Chemotherapy

Holmes AR, Keniya MV, Ivnitski-Steele I, Monk BC, Lamping E, Sklar LA, Cannon RD
Antimicrobial Agents and Chemotherapy - vol. 56 1508-1515 (2012)

Resistance to the commonly used azole antifungal fluconazole (FLC) can develop due to overexpression of ATP-binding cassette (ABC) and major facilitator superfamily (MFS) plasma membrane transporters. An approach to overcoming this resistance is to identify inhibitors of these efflux pumps. We have developed a pump assay suitable for high-throughput screening (HTS) that uses recombinant Saccharomyces […]

Publications

Development and Implementation of a High Throughput Screen for the Human Sperm-Specific Isoform of Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDHS).

Current chemical genomics

Sexton JZ, Danshina PV, Lamson DR, Hughes M, House AJ, Yeh L, O'Brien DA, Williams KP
Current chemical genomics - vol. 5 30-41 (2011)

Glycolytic isozymes that are restricted to the male germline are potential targets for the development of reversible, non-hormonal male contraceptives. GAPDHS, the sperm-specific isoform of glyceraldehyde-3-phosphate dehydrogenase, is an essential enzyme for glycolysis making it an attractive target for rational drug design. Toward this goal, we have optimized and validated a high-throughput spectrophotometric assay for […]

Publications

Novel chemical suppressors of long QT syndrome identified by an in vivo functional screen

Circulation

Peal DS, Mills RW, Lynch SN, Mosley JM, Lim E, Ellinor PT, January CT, Peterson RT, Milan DJ
Circulation - vol. 123 23-30 (2011)

BACKGROUND: Genetic long QT (LQT) syndrome is a life-threatening disorder caused by mutations that result in prolongation of cardiac repolarization. Recent work has demonstrated that a zebrafish model of LQT syndrome faithfully recapitulates several features of human disease, including prolongation of ventricular action potential duration, spontaneous early afterdepolarizations, and 2:1 atrioventricular block in early stages […]

Publications

Triclabendazole protects yeast and mammalian cells from oxidative stress: Identification of a potential neuroprotective compound

Biochemical and Biophysical Research Communications

Lee YJ, Burlet E, Wang S, Xu B, Huang S, Galiano FJ, Witt SN
Biochemical and Biophysical Research Communications - vol. 414 205-208 (2011)

The Prestwick and NIH chemical libraries were screened for drugs that protect baker’s yeast from sugar-induced cell death (SICD). SICD is triggered when stationary-phase yeast cells are transferred from spent rich medium into water with 2% glucose and no other nutrients. The rapid, apoptotic cell death occurs because reactive oxygen species (ROS) accumulate. We found […]

Publications

Drug screening in a zebrafish model of Duchenne muscular dystrophy.

Proceedings of the National Academy of Sciences of the United States of America

Kawahara G, Karpf JA, Myers JA, Alexander MS, Guyon JR, Kunkel LM
Proceedings of the National Academy of Sciences of the United States of America - vol. 108 5331-6 (2011)

Two known zebrafish dystrophin mutants, sapje and sapje-like (sap(c/100)), represent excellent small-animal models of human muscular dystrophy. Using these dystrophin-null zebrafish, we have screened the Prestwick chemical library for small molecules that modulate the muscle phenotype in these fish. With a quick and easy birefringence assay, we have identified seven small molecules that influence muscle […]

Publications

High-throughput fluorescence polarization assay to identify inhibitors of Cbl(TKB)-protein tyrosine kinase interactions

Analytical Biochemistry

Kumar EA, Charvet CD, Lokesh GL, Natarajan A
Analytical Biochemistry - vol. 411 254-260 (2011)

The casitas B-lineage lymphoma (Cbl) proteins play an important role in regulating signal transduction pathways by functioning as E3 ubiquitin ligases. The Cbl proteins contain a conserved tyrosine kinase binding (TKB) domain that binds more than a dozen proteins, including protein tyrosine kinases (PTKs), in a phosphorylation-dependent manner. The cell surface expression levels of the […]

Publications

Visual characterization and diversity quantification of chemical libraries: 1. Creation of delimited reference chemical subspaces

Journal of Chemical Information and Modeling

Le Guilloux V, Colliandre L, Bourg S, Guénegou G, Dubois-Chevalier J, Morin-Allory L
Journal of Chemical Information and Modeling - vol. 51 1762-1774 (2011)

High-throughput screening (HTS) is a well-established technology which can test up to several million compounds in a few weeks. Despite these appealing capabilities, available resources and high costs may limit the number of molecules screened, making diversity analysis a method of choice to design and prioritize screening libraries. With a constantly increasing number of molecules […]

Publications

Orthologue selectivity and ligand bias: Translating the pharmacology of GPR35

Trends in Pharmacological Sciences

Milligan G
Trends in Pharmacological Sciences - vol. 32 317-325 (2011)

GPR35 is a poorly characterized G protein-coupled receptor (GPCR) that has been suggested as a potential therapeutic target for the treatment of diabetes, hypertension and asthma. Two endogenously produced ligands have been suggested as activators of GPR35, although the relevance of these remains unclear. Recently, a series of surrogate agonist ligands and the first antagonists […]

Publications

Drug discovery for duchenne muscular dystrophy via utrophin promoter activation screening

PLoS ONE

Moorwood C, Lozynska O, Suri N, Napper AD, Diamond SL, Khurana TS
PLoS ONE - vol. 6 1-11 (2011)

BACKGROUND: Duchenne muscular dystrophy (DMD) is a devastating muscle wasting disease caused by mutations in dystrophin, a muscle cytoskeletal protein. Utrophin is a homologue of dystrophin that can functionally compensate for its absence when expressed at increased levels in the myofibre, as shown by studies in dystrophin-deficient mice. Utrophin upregulation is therefore a promising therapeutic […]

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