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Publications
A cell-based screening system for influenza A viral RNA transcription/replication inhibitors.

Scientific reports

Ozawa M, Shimojima M, Goto H, Watanabe S, Hatta Y, Kiso M, Furuta Y, Horimoto T, Peters NR, Hoffmann FM, Kawaoka Y
Scientific reports - vol. 3 1106 (2013)

Although two classes of antivirals, NA inhibitors and M2 ion channel blockers, are licensed for influenza treatment, dual resistant mutants, including highly pathogenic H5N1 viruses, have appeared. Alternative treatment options are, therefore, needed. Influenza A viral RNA (vRNA) transcription/replication is a promising target for antiviral development, since it is essential for virus replication. Accordingly, an […]

Publications
Dopamine D2 receptor antagonism suppresses tau aggregation and neurotoxicity

Biological Psychiatry

McCormick AV, Wheeler JM, Guthrie CR, Liachko NF, Kraemer BC
Biological Psychiatry - vol. 73 464-471 (2013)

Background: Tauopathies, including Alzheimer’s disease and frontotemporal dementia, are diseases characterized by the formation of pathological tau protein aggregates in the brain and progressive neurodegeneration. Presently no effective disease-modifying treatments exist for tauopathies. Methods: To identify drugs targeting tau neurotoxicity, we have used a Caenorhabditis elegans model of tauopathy to screen a drug library containing […]

Publications
In vitro assessment of Macleaya cordata crude extract bioactivity and anticancer properties in normal and cancerous human lung cells

Experimental and Toxicologic Pathology

Liu M, Lin YL, Chen XR, Liao CC, Poo WK
Experimental and Toxicologic Pathology - vol. 65 775-787 (2013)

The purpose of this study is to assess the bioactivity and anticancer properties of Macleaya cordata crude extract in vitro using normal fetal lung fibroblast MRC5 and adenocarcinomic epithelial cell A549 as model systems,. Treatment of extract induced cell detachment, rounding, and irregularity in shape, in both normal and adenocarcinomic human lung cells, in accompanied […]

Publications
Identification of small molecules that promote human embryonic stem cell self-renewal

Biochemical and Biophysical Research Communications

Kumagai H, Suemori H, Uesugi M, Nakatsuji N, Kawase E
Biochemical and Biophysical Research Communications - vol. 434 710-716 (2013)

Human embryonic stem cells (hESCs) and induced pluripotent cells have the potential to provide an unlimited source of tissues for regenerative medicine. For this purpose, development of defined/xeno-free culture systems under feeder-free conditions is essential for the expansion of hESCs. Most defined/xeno-free media for the culture of hESCs contain basic fibroblast growth factor (bFGF). Therefore, […]

Publications
An in vivo zebrafish screen identifies organophosphate antidotes with diverse mechanisms of action.

Journal of biomolecular screening

Jin S, Sarkar KS, Jin YN, Liu Y, Kokel D, Van Ham TJ, Roberts LD, Gerszten RE, Macrae CA, Peterson RT
Journal of biomolecular screening - vol. 18 108-115 (2013)

Organophosphates are a class of highly toxic chemicals that includes many pesticides and chemical weapons. Exposure to organophosphates, either through accidents or acts of terrorism, poses a significant risk to human health and safety. Existing antidotes, in use for over 50 years, have modest efficacy and undesirable toxicities. Therefore, discovering new organophosphate antidotes is a […]

Publications
Zebrafish based small molecule screens for novel DMD drugs

Drug Discovery Today: Technologies

Kawahara G, Kunkel LM
Drug Discovery Today: Technologies - vol. 10 e91-e96 (2013)

Recently, a number of chemical and drug screens using zebrafish embryos have been published. Using zebrafish dystrophin mutants, we screened a chemical library for small molecules that modulate the muscle phenotype and identified seven small molecules that influence muscle pathology in dystrophin-null zebrafish. One chemical, aminophylline, which is known to be a non-selective phosphodiesterase (PDE) […]

Publications
Hit identification of novel heparanase inhibitors by structure- and ligand-based approaches

Bioorganic and Medicinal Chemistry

Gozalbes R, Mosulén S, Ortí L, Rodríguez-Díaz J, Carbajo RJ, Melnyk P, Pineda-Lucena A
Bioorganic and Medicinal Chemistry - vol. 21 1944-1951 (2013)

Heparanase is a key enzyme involved in the dissemination of metastatic cancer cells. In this study a combination of in silico techniques and experimental methods was used to identify new potential inhibitors against this target. A 3D model of heparanase was built from sequence homology and applied to the virtual screening of a library composed […]

Publications
The immunosuppressive drug azathioprine inhibits biosynthesis of the bacterial signal molecule cyclic-di-GMP by interfering with intracellular nucleotide pool availability

Applied Microbiology and Biotechnology

Antoniani D, Rossi E, Rinaldo S, Bocci P, Lolicato M, Paiardini A, Raffaelli N, Cutruzzol?? F, Landini P
Applied Microbiology and Biotechnology - vol. 97 7325-7336 (2013)

In Gram-negative bacteria, production of the signal molecule c-di-GMP by diguanylate cyclases (DGCs) is a key trigger for biofilm formation, which, in turn, is often required for the development of chronic bacterial infections. Thus, DGCs represent interesting targets for new chemotherapeutic drugs with anti-biofilm activity. We searched for inhibitors of the WspR protein, a Pseudomonas […]

Publications
Animal models in therapeutic drug discovery for oculopharyngeal muscular dystrophy

Drug Discovery Today: Technologies

Chartier A, Simonelig M
Drug Discovery Today: Technologies - vol. 10 e103-e108 (2013)

Oculopharyngeal muscular dystrophy (OPMD) is a late onset disease which affects specific muscles. No pharmacological treatments are currently available for OPMD. In recent years, genetically tractable models of OPMD-Drosophila and Caenorhabditis elegans-have been generated. Although these models have not yet been used for large-scale primary drug screening, they have been very useful in candidate approaches […]

Publications
A cell-free fluorometric high-throughput screen for inhibitors of Rtt109-catalyzed histone acetylation

PLoS ONE

Dahlin JL, Sinville R, Solberg J, Zhou H, Han J, Francis S, Strasser JM, John K, Hook DJ, Walters MA, Zhang Z
PLoS ONE - vol. 8 (2013)

The lysine acetyltransferase (KAT) Rtt109 forms a complex with Vps75 and catalyzes the acetylation of histone H3 lysine 56 (H3K56ac) in the Asf1-H3-H4 complex. Rtt109 and H3K56ac are vital for replication-coupled nucleosome assembly and genotoxic resistance in yeast and pathogenic fungal species such as Candida albicans. Remarkably, sequence homologs of Rtt109 are absent in humans. […]