Archives des Publications - Page 31 sur 44 - Prestwick Chemical Libraries

Publications

Identification of inhibitors of vacuolar proton-translocating ATPase pumps in yeast by high-throughput screening flow cytometry

Analytical Biochemistry

Johnson RM, Allen C, Melman SD, Waller A, Young SM, Sklar LA, Parra KJ
Analytical Biochemistry - vol. 398 203-211 (2010)

Fluorescence intensity of the pH-sensitive carboxyfluorescein derivative 2,7-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) was monitored by high-throughput flow cytometry in living yeast cells. We measured fluorescence intensity of BCECF trapped in yeast vacuoles, acidic compartments equivalent to lysosomes where vacuolar proton-translocating ATPases (V-ATPases) are abundant. Because V-ATPases maintain a low pH in the vacuolar lumen, V-ATPase inhibition by concanamycin […]

Publications

Minigenome-based reporter system suitable for high-throughput screening of compounds able to inhibit Ebolavirus replication and/or transcription

Antimicrobial Agents and Chemotherapy

Jasenosky LD, Neumann G, Kawaoka Y
Antimicrobial Agents and Chemotherapy - vol. 54 3007-3010 (2010)

We describe an Ebolavirus minigenome-based system that is suitable for high-throughput screening of compounds able to impair Ebolavirus virus replication and/or transcription. The assay is robust (Z؅ factor, >0.6) and can be carried out in low-biosafety containment. Results from a pilot screen of 960 compounds are presented. Ebolaviruses and the closely related Marburgviruses cause hemorrhagic […]

Publications

Modulation of pantothenate kinase 3 activity by small molecules that interact with the substrate/allosteric regulatory domain

Chemistry and Biology

Leonardi R, Zhang YM, Yun MK, Zhou R, Zeng FY, Lin W, Cui J, Chen T, Rock CO, White SW, Jackowski S
Chemistry and Biology - vol. 17 892-902 (2010)

Pantothenate kinase (PanK) catalyzes the rate-controlling step in coenzyme A (CoA) biosynthesis. PanK3 is stringently regulated by acetyl-CoA and uses an ordered kinetic mechanism with ATP as the leading substrate. Biochemical analysis of site-directed mutants indicates that pantothenate binds in a tunnel adjacent to the active site that is occupied by the pantothenate moiety of […]

Publications

Identification of Hedgehog signaling inhibitors with relevant human exposure by small molecule screening

Toxicology in Vitro

Lipinski RJ, Bushman W
Toxicology in Vitro - vol. 24 1404-1409 (2010)

In animal models, chemical disruption of the Hedgehog (Hh) signaling pathway during embryonic development causes severe birth defects including holoprosencephaly and cleft lip and palate. The exact etiological basis of correlate human birth defects remains uncertain but is likely multifactorial, involving the interaction of genetic and environmental or chemical influences. The Hh transduction mechanism relies […]

Publications

Cell-based and cytokine-directed chemical screen to identify potential anti-multiple myeloma agents

Leukemia Research

Feng R, Rios JA, Onishi T, Lokshin A, Gorelik E, Lentzsch S
Leukemia Research - vol. 34 917-924 (2010)

We used a novel high-throughput drug screening assay, based on Luminex technology, to identify anti-myeloma agents capable of inhibiting cytokines and growth factors essential for multiple myeloma (MM) from a chemical library of 1120 compounds provided by MMRF. Tetracycline derivatives inhibited MM cell proliferation and osteoclast activating factors without obvious effect on cell viability. Steroid […]

Publications

Novel regulators of stem cell fates identified by a multivariate phenotype screen of small compounds on human embryonic stem cell colonies

Stem Cell Research

Barbaric I, Gokhale PJ, Jones M, Glen A, Baker D, Andrews PW
Stem Cell Research - vol. 5 104-119 (2010)

Understanding the complex mechanisms that govern the fate decisions of human embryonic stem cells (hESCs) is fundamental to their use in cell replacement therapies. The progress of dissecting these mechanisms will be facilitated by the availability of robust high-throughput screening assays on hESCs. In this study, we report an image-based high-content assay for detecting compounds […]

Publications

A fluorescent polarization-based assay for the identification of disruptors of the RCAN1-calcineurin A protein complex

Analytical Biochemistry

Carme Mulero M, Orz??ez M, Messeguer J, Messeguer ?, P??rez-Pay?? E, P??rez-Riba M
Analytical Biochemistry - vol. 398 99-103 (2010)

Calcineurin is a Ca2+/calmodulin-dependent serine/threonine protein phosphatase involved in many biological processes and developmental programs, including immune response. One of the most studied substrates of calcineurin is the transcription factor NFAT (nuclear factor of activated T cells) responsible for T-cell activation. Different anticalcineurin drugs, such as cyclosporine A and FK506, are the most commonly used […]

Publications

Monitoring of diguanylate cyclase activity and of cyclic-di-GMP biosynthesis by whole-cell assays suitable for high-throughput screening of biofilm inhibitors

Applied Microbiology and Biotechnology

Antoniani D, Bocci P, MacIa̧g A, Raffaelli N, Landini P
Applied Microbiology and Biotechnology - vol. 85 1095-1104 (2010)

In Gram-negative bacteria, production of bis-(3′,5′)-cyclic diguanylic acid (c-di-GMP) by diguanylate cyclases (DGCs) is the main trigger for production of extracellular polysaccharides and for biofilm formation. Mutants affected in c-di-GMP biosynthesis are impaired in biofilm formation, thus making DGCs interesting targets for new antimicrobial agents with anti-biofilm activity. In this report, we describe a strategy […]

Publications

Development of a cell-based high-throughput assay to screen for inhibitors of organic anion transporting polypeptides 1B1 and 1B3.

Current chemical genomics

Gui C, Obaidat A, Chaguturu R, Hagenbuch B
Current chemical genomics - vol. 4 1-8 (2010)

The two organic anion transporting polypeptides (OATPs) 1B1 and 1B3 are expressed at the sinusoidal membrane of hepatocytes. They have a broad and overlapping substrate specificity and transport many endobiotics and drugs. Specific inhibitors are required to determine the contribution of each OATP to the hepatocellular uptake of common substrates. We have developed a cell-based […]

Publications

Pharmacological targeting of the mitochondrial phosphatase PTPMT1.

The Journal of pharmacology and experimental therapeutics

Doughty-Shenton D, Joseph JD, Zhang J, Pagliarini DJ, Kim Y, Lu D, Dixon JE, Casey PJ
The Journal of pharmacology and experimental therapeutics - vol. 333 584-92 (2010)

The dual-specificity protein tyrosine phosphatases (PTPs) play integral roles in the regulation of cell signaling. There is a need for new tools to study these phosphatases, and the identification of inhibitors potentially affords not only new means for their study, but also possible therapeutics for the treatment of diseases caused by their dysregulation. However, the […]

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