Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
4.7
4.6
Journals
Pharmaceuticals
Special Issues
New Developments in High-Throughput Screening
share announcement

New Developments in High-Throughput Screening

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 12448

Special Issue Editors

Dr. Vytaute Starkuviene

E-Mail Website
Guest Editor
1. Universität Heidelberg, Heidelberg, Germany
2. Vilnius University, Vilnius, Lithuania
Interests: functional cell analysis; intracellular trafficking networks
Dr. Holger Erfle

E-Mail Website
Co-Guest Editor
Universität Heidelberg, Heidelberg, Germany
Interests: assay miniaturization and methods; high-content microscopy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

High-throughput screening has propelled basic research, drug discovery and development enormously in the last few years. Being applied for basic research, various screening approaches discover hundreds of novel regulators, functionally characterise short and long non-coding RNAs, identify generic and personalized disease risks and markers, reconstruct the entire regulatory networks in a spatial and temporal manner. Primarily, genetic screens, be it RNA interference (RNAi) or, lately, CRISPR-Cas9 mediated gene editing, are the most instrumental for these purposes. Genetic screens are also widely applied to complement chemical screens, to deconvolute drug targets or prioritize drug–target interactions. Initially being applied only for 2D cell culture models, high-throughput screening is moving to 3D cellular models with dramatically improved clinical relevance of the results.

The applications of high-throughput screening is closely related to technological progress. Automated fluorescence microscopy, sample miniaturization, microfluidics and single cell based analyses, effective intracellular delivery, reagents and strategies for gene editing approaches boosted screening and made it faster, better accessible and more cost-effective.

The journal Pharmaceuticals invites both reviews and original articles dealing with the advancement of high-throughput genetic and chemical screening and novel areas of applications. Topics include: sample miniaturization, physiological and clinically relevant cell and tissue models, novel imaging modalities, loss-of-function and gain-of-function modification strategies, combinatorial screening. Authors from both academic and industrial domains are welcome to submit their contributions. The collection of manuscripts will be published as a Special Issue of the journal.

Dr. Vytaute Starkuviene
Dr. Holger Erfle
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • high-throughput screening
  • expression modulation
  • RNA interference
  • CRISPR-Cas9 gene editing
  • chemical screening
  • arrayed and pooled screening
  • screening in 3D
  • microfluidics

Published Papers (4 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

31 pages, 4188 KiB  
Article
Beta and Gamma Amino Acid-Substituted Benzenesulfonamides as Inhibitors of Human Carbonic Anhydrases
by Benas Balandis, Tomas Šimkūnas, Vaida Paketurytė-Latvė, Vilma Michailovienė, Aurelija Mickevičiūtė, Elena Manakova, Saulius Gražulis, Sergey Belyakov, Visvaldas Kairys, Vytautas Mickevičius, Asta Zubrienė and Daumantas Matulis
Pharmaceuticals 2022, 15(4), 477; https://0-doi-org.brum.beds.ac.uk/10.3390/ph15040477 - 13 Apr 2022
Cited by 5 | Viewed by 2265
Abstract
A series of novel benzenesulfonamide derivatives were synthesized bearing para-N β,γ-amino acid or para-N β-amino acid and thiazole moieties and their binding to the human carbonic anhydrase (CA) isozymes determined. These enzymes are involved in various illnesses, such as [...] Read more.
A series of novel benzenesulfonamide derivatives were synthesized bearing para-N β,γ-amino acid or para-N β-amino acid and thiazole moieties and their binding to the human carbonic anhydrase (CA) isozymes determined. These enzymes are involved in various illnesses, such as glaucoma, altitude sickness, epilepsy, obesity, and even cancer. There are numerous compounds that are inhibitors of CA and used as pharmaceuticals. However, most of them bind to most CA isozymes with little selectivity. The design of high affinity and selectivity towards one CA isozyme remains a significant challenge. The beta and gamma amino acid-substituted compound affinities were determined by the fluorescent thermal shift assay and isothermal titration calorimetry for all 12 catalytically active human carbonic anhydrase isozymes, showing the full affinity and selectivity profile. The structures of several compounds were determined by X-ray crystallography, and the binding mode in the active site of CA enzyme was shown. Full article
(This article belongs to the Special Issue New Developments in High-Throughput Screening)
►▼ Show Figures

Graphical abstract

13 pages, 19326 KiB  
Article
Preclinical Drug Response Metric Based on Cellular Response Phenotype Provides Better Pharmacogenomic Variables with Phenotype Relevance
by Sanghyun Kim and Sohyun Hwang
Pharmaceuticals 2021, 14(12), 1324; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14121324 - 17 Dec 2021
Viewed by 2404
Abstract
High-throughput screening of drug response in cultured cell lines is essential for studying therapeutic mechanisms and identifying molecular variants associated with sensitivity to drugs. Assessment of drug response is typically performed by constructing a dose-response curve of viability and summarizing it to a [...] Read more.
High-throughput screening of drug response in cultured cell lines is essential for studying therapeutic mechanisms and identifying molecular variants associated with sensitivity to drugs. Assessment of drug response is typically performed by constructing a dose-response curve of viability and summarizing it to a representative, such as IC50. However, this is limited by its dependency on the assay duration and lack of reflections regarding actual cellular response phenotypes. To address these limitations, we consider how each response-phenotype contributes to the overall growth behavior and propose an alternative method of drug response screening that takes into account the cellular response phenotype. In conventional drug response screening methods, the ranking of sensitivity depends on either the metric used to construct the dose-response curve or the representative factor used to summarize the curve. This ambiguity in conventional assessment methods is due to the fact that assessment methods are not consistent with the underlying principles of population dynamics. Instead, the suggested phenotype metrics provide all phenotypic rates of change that shape overall growth behavior at a given dose and better response classification, including the phenotypic mechanism of overall growth inhibition. This alternative high-throughput drug-response screening would improve preclinical pharmacogenomic analysis and the understanding of a therapeutic mechanism of action. Full article
(This article belongs to the Special Issue New Developments in High-Throughput Screening)
►▼ Show Figures

Graphical abstract

13 pages, 2424 KiB  
Article
High-Throughput Phenotypic Assay to Screen for Anthelmintic Activity on Haemonchus contortus
by Aya C. Taki, Joseph J. Byrne, Tao Wang, Brad E. Sleebs, Nghi Nguyen, Ross S. Hall, Pasi K. Korhonen, Bill C.H. Chang, Paul Jackson, Abdul Jabbar and Robin B. Gasser
Pharmaceuticals 2021, 14(7), 616; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14070616 - 26 Jun 2021
Cited by 22 | Viewed by 3086
Abstract
Parasitic worms cause very significant diseases in animals and humans worldwide, and their control is critical to enhance health, well-being and productivity. Due to widespread drug resistance in many parasitic worms of animals globally, there is a major, continuing demand for the discovery [...] Read more.
Parasitic worms cause very significant diseases in animals and humans worldwide, and their control is critical to enhance health, well-being and productivity. Due to widespread drug resistance in many parasitic worms of animals globally, there is a major, continuing demand for the discovery and development of anthelmintic drugs for use to control these worms. Here, we established a practical, cost-effective and semi-automated high throughput screening (HTS) assay, which relies on the measurement of motility of larvae of the barber’s pole worm (Haemonchus contortus) using infrared light-interference. Using this assay, we screened 80,500 small molecules and achieved a hit rate of 0.05%. We identified three small molecules that reproducibly inhibited larval motility and/or development (IC50 values of ~4 to 41 µM). Future work will critically assess the potential of selected hits as candidates for subsequent optimisation or repurposing against parasitic nematodes. This HTS assay has a major advantage over most previous assays in that it achieves a ≥ 10-times higher throughput (i.e., 10,000 compounds per week), and is thus suited to the screening of libraries of tens of thousands to hundreds of thousands of compounds for subsequent hit-to-lead optimisation or effective repurposing and development. The current assay should be adaptable to many socioeconomically important parasitic nematodes, including those that cause neglected tropical diseases (NTDs). This aspect is of relevance, given the goals of the World Health Organization (WHO) Roadmap for NTDs 2021–2030, to develop more effective drugs and drug combinations to improve patient outcomes and circumvent the ineffectiveness of some current anthelmintic drugs and possible drug resistance. Full article
(This article belongs to the Special Issue New Developments in High-Throughput Screening)
►▼ Show Figures

Figure 1

45 pages, 6391 KiB  
Article
Discovery of Novel Chemical Series of OXA-48 β-Lactamase Inhibitors by High-Throughput Screening
by Barbara Garofalo, Federica Prati, Rosa Buonfiglio, Isabella Coletta, Noemi D’Atanasio, Angela Molteni, Daniele Carettoni, Valeria Wanke, Giorgio Pochetti, Roberta Montanari, Davide Capelli, Claudio Milanese, Francesco Paolo Di Giorgio and Rosella Ombrato
Pharmaceuticals 2021, 14(7), 612; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14070612 - 25 Jun 2021
Cited by 4 | Viewed by 3710
Abstract
The major cause of bacterial resistance to β-lactams is the production of hydrolytic β-lactamase enzymes. Nowadays, the combination of β-lactam antibiotics with β-lactamase inhibitors (BLIs) is the main strategy for overcoming such issues. Nevertheless, particularly challenging β-lactamases, such as OXA-48, pose the need [...] Read more.
The major cause of bacterial resistance to β-lactams is the production of hydrolytic β-lactamase enzymes. Nowadays, the combination of β-lactam antibiotics with β-lactamase inhibitors (BLIs) is the main strategy for overcoming such issues. Nevertheless, particularly challenging β-lactamases, such as OXA-48, pose the need for novel and effective treatments. Herein, we describe the screening of a proprietary compound collection against Klebsiella pneumoniae OXA-48, leading to the identification of several chemotypes, like the 4-ideneamino-4H-1,2,4-triazole (SC_2) and pyrazolo[3,4-b]pyridine (SC_7) cores as potential inhibitors. Importantly, the most potent representative of the latter series (ID2, AC50 = 0.99 μM) inhibited OXA-48 via a reversible and competitive mechanism of action, as demonstrated by biochemical and X-ray studies; furthermore, it slightly improved imipenem’s activity in Escherichia coli ATCC BAA-2523 β-lactam resistant strain. Also, ID2 showed good solubility and no sign of toxicity up to the highest tested concentration, resulting in a promising starting point for further optimization programs toward novel and effective non-β-lactam BLIs. Full article
(This article belongs to the Special Issue New Developments in High-Throughput Screening)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-4
Back to TopTop