scholarly journals Targeting Wall Techoic Acid Biosynthesis: An in Vivo Based High-Throughput Screen for Small Molecule Inhibitors

2009 ◽  
Vol 4 (11) ◽  
pp. 893-894 ◽  
Author(s):  
Wenlan Chen ◽  
Robert Woodward ◽  
Peng George Wang
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
Small Molecule Inhibitors ◽  
High Throughput Screen ◽  
Acid Biosynthesis

scholarly journals Cell‐based high‐throughput screen for small molecule inhibitors of Bax translocation

2018 ◽  
Vol 23 (3) ◽  
pp. 1784-1797 ◽  
Author(s):  
Kelvin Kai‐Wan Hui ◽  
Chesarahmia Dojo Soeandy ◽  
Stephano Chang ◽  
Frederick S. Vizeacoumar ◽  
Thomas Sun ◽  
...  
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
Small Molecule Inhibitors ◽  
High Throughput Screen

scholarly journals A High-Throughput Cellular Screening Assay for Small-Molecule Inhibitors and Activators of Cytoplasmic Dynein-1-Based Cargo Transport

2020 ◽  
Vol 25 (9) ◽  
pp. 985-999
Author(s):  
John Vincent ◽  
Marian Preston ◽  
Elizabeth Mouchet ◽  
Nicolas Laugier ◽  
Adam Corrigan ◽  
...  
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
High Throughput Screening ◽  
Small Molecule Inhibitors ◽  
Cytoplasmic Dynein ◽  
Lead Discovery ◽  
Screening Assay ◽  
Age Related ◽  
The Uk

Cytoplasmic dynein-1 (hereafter dynein) is a six-subunit motor complex that transports a variety of cellular components and pathogens along microtubules. Dynein’s cellular functions are only partially understood, and potent and specific small-molecule inhibitors and activators of this motor would be valuable for addressing this issue. It has also been hypothesized that an inhibitor of dynein-based transport could be used in antiviral or antimitotic therapy, whereas an activator could alleviate age-related neurodegenerative diseases by enhancing microtubule-based transport in axons. Here, we present the first high-throughput screening (HTS) assay capable of identifying both activators and inhibitors of dynein-based transport. This project is also the first collaborative screening report from the Medical Research Council and AstraZeneca agreement to form the UK Centre for Lead Discovery. A cellular imaging assay was used, involving chemically controlled recruitment of activated dynein complexes to peroxisomes. Such a system has the potential to identify molecules that affect multiple aspects of dynein biology in vivo. Following optimization of key parameters, the assay was developed in a 384-well format with semiautomated liquid handling and image acquisition. Testing of more than 500,000 compounds identified both inhibitors and activators of dynein-based transport in multiple chemical series. Additional analysis indicated that many of the identified compounds do not affect the integrity of the microtubule cytoskeleton and are therefore candidates to directly target the transport machinery.

scholarly journals Small Molecule Inhibitors of Phospholipase C from a Novel High-throughput Screen

2013 ◽  
Vol 288 (8) ◽  
pp. 5840-5848 ◽  
Author(s):  
Weigang Huang ◽  
Matthew Barrett ◽  
Nicole Hajicek ◽  
Stephanie Hicks ◽  
T. Kendall Harden ◽  
...  
Keyword(s):  
Phospholipase C ◽  
Small Molecule ◽  
High Throughput ◽  
Small Molecule Inhibitors ◽  
High Throughput Screen

scholarly journals A Target-Based High Throughput Screen Yields Trypanosoma brucei Hexokinase Small Molecule Inhibitors with Antiparasitic Activity

2010 ◽  
Vol 4 (4) ◽  
pp. e659 ◽  
Author(s):  
Elizabeth R. Sharlow ◽  
Todd A. Lyda ◽  
Heidi C. Dodson ◽  
Gabriela Mustata ◽  
Meredith T. Morris ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Small Molecule ◽  
High Throughput ◽  
Small Molecule Inhibitors ◽  
High Throughput Screen ◽  
Antiparasitic Activity

scholarly journals A high-throughput screen to identify novel small molecule inhibitors of the Werner Syndrome Helicase-Nuclease (WRN)

PLoS ONE ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. e0210525 ◽  
Author(s):  
Joshua A. Sommers ◽  
Tomasz Kulikowicz ◽  
Deborah L. Croteau ◽  
Thomas Dexheimer ◽  
Dorjbal Dorjsuren ◽  
...  
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
Small Molecule Inhibitors ◽  
Werner Syndrome ◽  
High Throughput Screen

scholarly journals Small-Molecule Inhibitors of toxT Expression in Vibrio cholerae

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Rebecca Anthouard ◽  
Victor J. DiRita
Keyword(s):  
Cholera Toxin ◽  
Vibrio Cholerae ◽  
Small Molecule ◽  
High Throughput ◽  
Small Molecule Inhibitors ◽  
Severe Disease ◽  
Virulence Gene ◽  
High Throughput Screen ◽  
Content Type ◽  
Oral Rehydration

ABSTRACTVibrio cholerae, a Gram-negative bacterium, infects humans and causes cholera, a severe disease characterized by vomiting and diarrhea. These symptoms are primarily caused by cholera toxin (CT), whose production byV. choleraeis tightly regulated by the virulence cascade. In this study, we designed and carried out a high-throughput chemical genetic screen to identify inhibitors of the virulence cascade. We identified three compounds, which we named toxtazin A and toxtazin B and Bʹ, representing two novel classes oftoxTtranscription inhibitors. All three compounds reduce production of both CT and the toxin-coregulated pilus (TCP), an important colonization factor. We present evidence that toxtazin A works at the level of thetoxTpromoter and that toxtazins B and Bʹ work at the level of thetcpPpromoter. Treatment with toxtazin B results in a 100-fold reduction in colonization in an infant mouse model of infection, though toxtazin A did not reduce colonization at the concentrations tested. These results add to the growing body of literature indicating that small-molecule inhibitors of virulence genes could be developed to treat infections, as alternatives to antibiotics become increasingly needed.IMPORTANCEV. choleraecaused more than 580,000 infections worldwide in 2011 alone (WHO, Wkly. Epidemiol. Rec. 87:289-304, 2012). Cholera is treated with an oral rehydration therapy consisting of water, glucose, and electrolytes. However, asV. choleraeis transmitted via contaminated water, treatment can be difficult for communities whose water source is contaminated. In this study, we address the need for new therapeutic approaches by targeting the production of the main virulence factor, cholera toxin (CT). The high-throughput screen presented here led to the identification of two novel classes of inhibitors of the virulence cascade inV. cholerae, toxtazin A and toxtazins B and Bʹ. We demonstrate that (i) small-molecule inhibitors of virulence gene production can be identified in a high-throughput screen, (ii) targeting virulence gene production is an effective therapeutic strategy, and (iii) small-molecule inhibitors can uncover unknown layers of gene regulation, even in well-studied regulatory cascades.

scholarly journals Identification of small-molecule inhibitors of ricin and shiga toxin using a cell-based high-throughput screen

Toxicon ◽  
2010 ◽  
Vol 56 (3) ◽  
pp. 313-323 ◽  
Author(s):  
Paul G. Wahome ◽  
Yan Bai ◽  
Lori M. Neal ◽  
Jon D. Robertus ◽  
Nicholas J. Mantis
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
Shiga Toxin ◽  
Small Molecule Inhibitors ◽  
High Throughput Screen ◽  
A Cell
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