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Wednesday, November 9, 2016
Call For Paper
Bentham Science Publishers would like to invite you to submit your research paper for publishing in the Journal of
Combinatorial Chemistry & High Throughput Screening
Combinatorial Chemistry & High Throughput Screening
Wednesday, November 2, 2016
Highlighted Article: Proteases and their Inhibitors: From Basic to High Throughput Screening
Proteases and their Inhibitors: From Basic to High Throughput Screening
Author(s):
Leticia Casas-Godoy and Georgina Sandoval Pages 636 - 643 ( 8 )
Abstract:
Proteases constitute one of the most important groups of industrial enzymes with a worldwide value expected to reach 2.7 billion US dollars by 2019. Proteases represent a group of enzymes that hydrolyze the peptide bonds of proteins, releasing polypeptides or free amino acids. These enzymes are used in cleaning products, production of leathers, textiles, food and dairy products, in the pharmaceutical and diagnostic industries and for water treatment. Another area of interest regarding proteases is the development of drugs that act as protease inhibitors. This review will briefly describe the general methods used in the detection of proteases and the few studies in the development of high throughput screening methods of proteases and protease inhibitors.
Keywords:
Proteases, inhibitors, high throughput screening.
Affiliation:
CIATEJ, Av. Normalistas 800, 44270 Guadalajara, Jalisco, Mexico.
For More Information please Visit Our Website Combinatorial Chemistry & High Throughput Screening
Tuesday, October 25, 2016
Most Cited Article: ChemScreener: A Distributed Computing Tool for Scaffold based Virtual Screening
ChemScreener: A Distributed
Computing Tool for Scaffold based Virtual Screening
Author(s):
Muthukumarasamy Karthikeyan, Deepak Pandit and Renu VyasPages
544-561 (18)
Abstract:
In this work we present ChemScreener, a Java-based application to perform virtual library generation combined with virtual screening in a platform-independent distributed computing environment. ChemScreener comprises a scaffold identifier, a distinct scaffold extractor, an interactive virtual library generator as well as a virtual screening module for subsequently selecting putative bioactive molecules. The virtual libraries are annotated with chemophore-, pharmacophore- and toxicophore-based information for compound prioritization. The hits selected can then be further processed using QSAR, docking and other in silico approaches which can all be interfaced within the ChemScreener framework. As a sample application, in this work scaffold selectivity, diversity, connectivity and promiscuity towards six important therapeutic classes have been studied. In order to illustrate the computational power of the application, 55 scaffolds extracted from 161 anti-psychotic compounds were enumerated to produce a virtual library comprising 118 million compounds (17 GB) and annotated with chemophore, pharmacophore and toxicophore based features in a single step which would be non-trivial to perform with many standard software tools today on libraries of this size.
Keywords:
Scaffold extraction, therapeutic category, virtual library
generation, virtual screening.
Affiliation:
Digital Information Resource Centre, CSIR- National Chemical
Laboratory, Pune- 411008, India.
For More Information Please Visit Our Website Combinatorial Chemistry & High Throughput Screening
Wednesday, October 19, 2016
Podcast on Synthesis, Bioluminescence Inhibition, Molecular Docking Studies, Antibacterial Activities
Podcast on Synthesis, Bioluminescence Inhibition, Molecular Docking Studies, Antibacterial Activities
Wednesday, October 5, 2016
New Issue ::: Combinatorial Chemistry & High Throughput Screening, 19 Issue 8
Combinatorial Chemistry & High Throughput Screening(CCHTS) publishes full length original research articles and reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research.
The journal should be of value to individuals engaged in the process of drug discovery and development, in the settings of industry, academia or government.
Articles from the journal Combinatorial Chemistry & High Throughput Screening, Volume 19 Issue 8:
- Editorial (Thematic Issue: An Update of HTS for Selected Hydrolases)
- High Throughput Screening of Esterases, Lipases and Phospholipases in Mutant and Metagenomic Libraries: A Review
- From Classical to High Throughput Screening Methods for Feruloyl Esterases: A Review
- High Throughput Screening: Developed Techniques for Cellulolytic and Xylanolytic Activities Assay
- Proteases and their Inhibitors: From Basic to High Throughput Screening
- Identification of Novel PPARα/γ Dual Agonists by Virtual Screening of Specs Database
- Structure-Activity Relationship Studies on Holy Basil (Ocimum sanctum L.) Based Flavonoid Orientin and its Analogue for Cytotoxic Activity in Liver Cancer Cell Line HepG2
- Cheminformatics Based Machine Learning Approaches for Assessing Glycolytic Pathway Antagonists of Mycobacterium tuberculosis
- The Utilization of the Monte Carlo Technique for Rational Drug Discovery
For details on the articles, please visit this link :: http://bit.ly/2dC1Qqe
courtesy by : Bentham Insight
Combinatorial Chemistry & High Throughput Screening, 19 Issue 8
Combinatorial Chemistry & High Throughput Screening(CCHTS) publishes full length original research articles and reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research.
The journal should be of value to individuals engaged in the process of drug discovery and development, in the settings of industry, academia or government.
Articles from the journal Combinatorial Chemistry & High Throughput Screening, Volume 19 Issue 8:
- Editorial (Thematic Issue: An Update of HTS for Selected Hydrolases)
- High Throughput Screening of Esterases, Lipases and Phospholipases in Mutant and Metagenomic Libraries: A Review
- From Classical to High Throughput Screening Methods for Feruloyl Esterases: A Review
- High Throughput Screening: Developed Techniques for Cellulolytic and Xylanolytic Activities Assay
- Proteases and their Inhibitors: From Basic to High Throughput Screening
- Identification of Novel PPARα/γ Dual Agonists by Virtual Screening of Specs Database
- Structure-Activity Relationship Studies on Holy Basil (Ocimum sanctum L.) Based Flavonoid Orientin and its Analogue for Cytotoxic Activity in Liver Cancer Cell Line HepG2
- Cheminformatics Based Machine Learning Approaches for Assessing Glycolytic Pathway Antagonists of Mycobacterium tuberculosis
- The Utilization of the Monte Carlo Technique for Rational Drug Discovery
For details on the articles, please visit this link :: http://bit.ly/2dC1Qqe
courtesy by : Bentham Insight
Combinatorial Chemistry & High Throughput Screening, 19 Issue 7
Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal:
- Target identification and validation
- Assay design, development, miniaturization and comparison
- High throughput/high content/in silico screening and associated technologies
- Label-free detection technologies and applications
- Stem cell technologies
- Biomarkers
- ADMET/PK/PD methodologies and screening
- Probe discovery and development, hit to lead optimization
- Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries)
- Chemical library design and chemical diversity
- Chemo/bio-informatics, data mining
- Compound management
- Pharmacognosy
- Drug repurposing
- Data management and statistical analysis
- Laboratory automation, robotics, microfluidics, signal detection technologies
- Current & Future Institutional Research Profile
- Technology transfer, legal and licensing issues
- Patents
In these respective subject areas, Combinatorial Chemistry & High Throughput Screening is intended to function as the most comprehensive and up-to-date medium available. The journal should be of value to individuals engaged in the process of drug discovery and development, in the settings of industry, academia or government.
Articles from the journal Combinatorial Chemistry & High Throughput Screening, 19 Issue 7
- Editorial (Thematic Issue: Medicinal Chemistry Applied to Natural Products in Neglected Drug Discovery)
- An In-Silico Investigation of Phytochemicals as Antiviral Agents Against Dengue Fever
- Natural Products as a Source for Antileishmanial and Antitrypanosomal Agents
- Management and Treatment of Dengue and Chikungunya – Natural Products to the Rescue
- δ-Cadinene,Calarene and δ-4-Carene from Kadsura heteroclita Essential Oil as Novel Larvicides Against Malaria, Dengue and Filariasis Mosquitoes
- Virtual Screening Techniques to Probe the Antimalarial Activity of some Traditionally Used Phytochemicals
- Rapid and Efficient One-Pot Synthesis of 3,4-Dihydroquinoxalin-2-Amine Derivatives Catalyzed by Co3O4@SiO2Core-Shell Nanoparticles Under Ultrasound Irradiation
For details on the articles, please visit this link :: http://bit.ly/2ba5lDO
courtesy by : Bentham Insight
Combinatorial Chemistry & High Throughput Screening
Combinatorial Chemistry & High Throughput Screening(CCHTS) publishes full length original research articles and reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research.
Articles from the journal Combinatorial Chemistry & High Throughput Screening, Volume 19 Issue 3:
- Editorial: Validate and Verify: Keys to Scientific Excellence
- High Throughput Screening for Colorectal Cancer Specific Compounds
- An Efficient Four-Step Approach Toward Fused Triazino[1,6-a] Quinazolines
- Synthesis and Antifeedant Activities of Rosin-Based Esters Against Armyworm
- Comprehensive Chemical Profiling of Picrorhiza kurroa Royle ex Benth Using NMR, HPTLC and LC-MS/MS Techniques
- Identification of Potent Virtual Leads Specific to S1’ Loop of ADAMTS4: Pharmacophore Modeling, 3D-QSAR, Molecular Docking and Dynamic Studies
- Structure-Based Virtual Screening for Defeating Drug Resistant Form of EGFR Protein
- Fragment-Based De Novo Design of Antimycobacterial Agents and In Vitro Potency Evaluation
- Insights from Analysis of Binding Sites of Human Meprins: Screening of Inhibitors by Molecular Dynamics Simulation Study
For details on the articles, please visit this link :: http://bit.ly/1T3QHXQ
courtesy by : Bentham Insight
Monday, July 11, 2016
Chemical Informatics and the Drug Discovery Knowledge Pyramid
Author(s):
Gerald H. Lushington, Yinghua Dong and Bhargav TheerthamPages 764-776 (13)
Abstract:
The magnitude of the challenges in preclinical drug discovery is evident in the large amount of capital invested in such efforts in pursuit of a small static number of eventually successful marketable therapeutics. An explosion in the availability of potentially drug-like compounds and chemical biology data on these molecules can provide us with the means to improve the eventual success rates for compounds being considered at the preclinical level, but only if the community is able to access available information in an efficient and meaningful way. Thus, chemical database resources are critical to any serious drug discovery effort. This paper explores the basic principles underlying the development and implementation of chemical databases, and examines key issues of how molecular information may be encoded within these databases so as to enhance the likelihood that users will be able to extract meaningful information from data queries. In addition to a broad survey of conventional data representation and query strategies, key enabling technologies such as new context-sensitive chemical similarity measures and chemical cartridges are examined, with recommendations on how such resources may be integrated into a practical database environment.
Keywords:
Chemical cartridge, chemical database, fingerprints, frequent subgraphs, hashing, molecular structure representation, similarity.
Affiliation:
LiS Consulting, 2933 Lankford Dr., Lawrence, KS 66046, USA.
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Digital Holographic Microscopy: A Quantitative Label-Free Microscopy Technique for Phenotypic Screening
Author(s):
Benjamin Rappaz, Billy Breton, Etienne Shaffer and Gerardo TurcattiPages 80-88 (9)
Abstract:
Digital Holographic Microscopy (DHM) is a label-free imaging technique allowing visualization of transparent cells with classical imaging cell culture plates. The quantitative DHM phase contrast image provided is related both to the intracellular refractive index and to cell thickness.
DHM is able to distinguish cellular morphological changes on two representative cell lines (HeLa and H9c2) when treated with doxorubicin and chloroquine, two cytotoxic compounds yielding distinct phenotypes. We analyzed parameters linked to cell morphology and to the intracellular content in endpoint measurements and further investigated them with timelapse recording. The results obtained by DHM were compared with other optical label-free microscopy techniques, namely Phase Contrast, Differential Interference Contrast and Transport of Intensity Equation (reconstructed from three bright-field images). For comparative purposes, images were acquired in a common 96-well plate format on the different motorized microscopes.
In contrast to the other microscopies assayed, images generated with DHM can be easily quantified using a simple automatized on-the-fly analysis method for discriminating the different phenotypes generated in each cell line. The DHM technology is suitable for the development of robust and unbiased image-based assays.
Keywords:
Cell-based assay, differential interference contrast, digital holography, high-content screening, image-based screen, phase contrast, phenotypic drug discovery.
Affiliation:
Biomolecular Screening Facility, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 15, Lausanne 1015, Switzerland.
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Discovery of MINC1, a GTPase-Activating Protein Small Molecule Inhibitor, Targeting MgcRacGAP
Author(s):
Arjan J. van Adrichem, Annika Fagerholm, Laura Turunen, Anna Lehto, Jani Saarela, Ari Koskinen, Gretchen A. Repasky and Krister WennerbergPages 3-17 (15)
Abstract:
The Rho family of Ras superfamily small GTPases regulates a broad range of biological processes such as migration, differentiation, cell growth and cell survival. Therefore, the availability of small molecule modulators as tool compounds could greatly enhance research on these proteins and their biological function. To this end, we designed a biochemical, high throughput screening assay with complementary follow-up assays to identify small molecule compounds inhibiting MgcRacGAP, a Rho family GTPase activating protein involved in cytokinesis and transcriptionally upregulated in many cancers. We first performed an in-house screen of 20,480 compounds, and later we tested the assay against 342,046 compounds from the NIH Molecular Libraries Small Molecule Repository. Primary screening hit rates were about 1% with the majority of those affecting the primary readout, an enzyme-coupled GDP detection assay. After orthogonal and counter screens, we identified two hits with high selectivity towards MgcRacGAP, compared with other RhoGAPs, and potencies in the low micromolar range. The most promising hit, termed MINC1, was then examined with cell-based testing where it was observed to induce an increased rate of cytokinetic failure and multinucleation in addition to other cell division defects, suggesting that it may act as an MgcRacGAP inhibitor also in cells.
Keywords:
Biochemical assays, cytokinesis, HTS, MgcRacGAP, Rac1, small molecule inhibitor.
Affiliation:
Institute for Molecular Medicine Finland FIMM, Nordic EMBL Partnership for Molecular Medicine, Biomedicum Helsinki 2U, P.O. Box 20 (Tukholmankatu 8), FI- 00014, University of Helsinki, Finland.
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High Throughput Screening of Esterases, Lipases and Phospholipases in Mutant and Metagenomic Libraries: A Review
Author(s):
Carlina Peña-García, Mónica Martínez-Martínez, Dolores Reyes-Duarte and Manuel FerrerPages 1-11 (11)
Abstract:
Nowadays, enzymes can be efficiently identified and screened from metagenomic resources or mutant libraries. A set of a few hundred new enzymes can be found using a simple substrate within few months. Hence, the establishment of an enzymes collection is no longer a big hurdle. However, a key problem is the relatively low rate of positive hits and that a timeline of several years from the identification of a gene to the development of a process is the reality rather than the exception. Major problems are related to the time-consuming and cost-intensive screening process that only very few enzymes finally pass. Accessing to the highest possible enzyme and mutant diversity by different, but complementary approaches is increasingly important. The aim of this review is to deliver state-of-art status of traditional and novel screening protocols for targeting lipases, esterases and phospholipases of industrial relevance, and that can be applied at high throughput scale (HTS) for at least 200 distinct substrates, at a speed of more than 105 – 108 clones/day. We also review fine-tuning sequence analysis pipelines and in silico tools, which can further improve enzyme selection by an unprecedent speed (up to 1030 enzymes). If the hit rate in an enzyme collection could be increased by HTS approaches, it can be expected that also the very further expensive and time-consuming enzyme optimization phase could be significantly shortened, as the processes of enzyme-candidate selection by such methods can be adapted to conditions most likely similar to the ones needed at industrial scale.
Keywords:
Biocatalysts, esterases, high throughput screening, lipases, metagenomic, phospholipases, protein engineering
Affiliation:
Departamento de Procesos y Tecnología, Universidad Autónoma Metropolitana, Unidad Cuajimalpa, Av. Vasco de Quiroga 4871, Col. Santa Fe, Deleg. Cuajimalpa, 05348, D.F, México, Institute of Catalysis, Consejo Superior de Investigaciones Científicas (CSIC), Marie Curie 2, 28049 Madrid, Spain
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Identification of Protein Palmitoylation Inhibitors from a Scaffold Ranking Library
Author(s):
Laura D. Hamel, Brian J. Lenhart, David A. Mitchell, Radleigh G. Santos, Marc A. Giulianotti and Robert J. DeschenesPages 262-274 (13)
Abstract:
The addition of palmitoyl moieties to proteins regulates their membrane targeting, subcellular localization, and stability. Dysregulation of the enzymes which catalyzed the palmitoyl addition and/or the substrates of these enzymes have been linked to cancer, cardiovascular, and neurological disorders, implying these enzymes and substrates are valid targets for pharmaceutical intervention. However, current chemical modulators of zDHHC PAT enzymes lack specificity and affinity, underscoring the need for screening campaigns to identify new specific, high affinity modulators. This report describes a mixture based screening approach to identify inhibitors of Erf2 activity. Erf2 is the Saccharomyces cerevisiae PAT responsible for catalyzing the palmitoylation of Ras2, an ortholog of the human Ras oncogene proteins. A chemical library developed by the Torrey Pines Institute for Molecular Studies consists of more than 30 million compounds designed around 68 molecular scaffolds that are systematically arranged into positional scanning and scaffold ranking formats. We have used this approach to identify and characterize several scaffold backbones and R-groups that reduce or eliminate the activity of Erf2 in vitro. Here, we present the analysis of one of the scaffold backbones, bis-cyclic piperazine. We identified compounds that inhibited Erf2 auto-palmitoylation activity using a fluorescence-based, coupled assay in a high throughput screening (HTS) format and validated the hits utilizing an orthogonal gel-based assay. Finally, we examined the effects of the compounds on cell growth in a yeast cell-based assay. Based on our results, we have identified specific, high affinity palmitoyl transferase inhibitors that will serve as a foundation for future compound design.
Keywords:
Acyltransferase, bis-cyclic piperazine, Erf2, enzyme inhibitor, high throughput screening (HTS), palmitoylation, zDHHC.
Affiliation:
Department of Molecular Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC07, Tampa, FL 33612, USA.
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