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HTS (High Throughput Screening) - Articles and news items
Over the past decades, pharmaceutical drug development has undergone some significant changes, a prominent example for this being the emergence of biomolecular drugs (New Biological Entities, NBEs) such as antibodies and peptides. However, classical small molecule drugs (New Chemical Entities, NCEs) are far from being a dying species, and in fact the number of NCE drugs approved by the US Food and Drug Administration (FDA) in the past few years has been higher with increasing trend compared to NBE drugs, which appear to stagnate at lower level in terms of new drug approvals…
Issue 6 2013, Screening, Supplements, Z Homepage promo / 16 December 2013 / Roger Clark, Paul Harper and Mark Wigglesworth (AstraZeneca Global High Throughput Centre), Rob Jepras and Steve Ludbrook (GlaxoSmithKline)
Technological and sociological advances in HTS: evolution and revolution?
Flow cytometry as a drug screening platform
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Drug Discovery, Issue 6 2013 / 15 December 2013 / Sergio C. Chai, Asli N. Goktug and Taosheng Chen, High Throughput Screening Center, Department of Chemical Biology and Therapeutics, St. Jude Children’s Research Hospital
Liquid handlers are ubiquitous and essential tools in every aspect of the drug discovery arena. Innovations in the past few decades resulted in a sizeable array of devices. With so many choices, it is important to identify appropriate instrumentation for a particular screening strategy, which should be based on unique capabilities and limitations…
Autophagy is a cellular stress response to diverse stimuli such as starvation, infection and DNA damage. Autophagy plays important roles in the progression of various diseases including cancer, neurodegenerative diseases and Crohn’s disease. Despite recent advances in our understanding of the autophagy machinery, surprisingly little effort has been undertaken towards utilising this knowledge in drug discovery processes. Several phenotypic screens have been undertaken to identify drug candidates that modulate this process. Current highthroughput screening approaches assay the formation of the autophagosome and very little effort is made towards the identification of compounds that inhibit specific autophagy components. Here, I give an overview about potential molecular drug targets in the autophagy pathway and review the current status of targeted drug discovery towards identifying autophagy gene-specific drugs.
Although many of the marketed small molecule drugs have been discovered by research and development efforts within the pharmaceutical industry, there has been a paradigm shift with external sources increasingly being relied upon to fill their pipelines. This trend is likely to increase and the key pre-clinical activities carried out by organisations outside the pharmaceutical industry include target validation, assay development and their use in High Throughput Screening campaigns, validation of the Hit molecules, Hit-to-Lead and Lead-to-Candidate screening/chemistry. In order to perform these activities, adequate know-how and technical expertise is essential so that the processes meet appropriate industry standards. This article discusses some of the challenges associated with assay development and the automation of High Throughput Screening.
Deciphering crude proteomes in the quest for candidate biomarker signatures for disease diagnostics, prognostics and classifications has proven to be challenging using conventional proteomic technologies. In this context, affinity protein microarrays, and in particular recombinant antibody microarrays, have recently been established as a promising approach within high-throughput (disease) proteomics1-3. The technology will provide miniaturised set-ups capable of profiling numerous protein analytes in a sensitive, selective and multiplexed manner.
The majority of active pharmaceutical ingredients (APIs) are produced by crystallisation and so the phenomenon of polymorphism, whereby an organic molecule can adopt more than one crystalline form (Figure 1 opposite), is of considerable importance when trying to achieve consistent product quality during the manufacture of pharmaceutical solids and solid dosage forms. Although morphology and particle size-distribution are important solid-state characteristics, the uncontrolled occurrence of multiple physical forms (polymorphs, solvates, salts, co-crystals or amorphous) of an API can have significant effects on the performance of the material during processing, manufacture, storage and administration. For example, the solubility difference between some polymorphs has been shown to be over four times that of the least soluble form1 and can vary by significantly more for amorphous forms2.
Back in May, it was announced that new stem cell research would reduce the need for animal testing…
Over the last 15 years, vendors have offered microscope-based instruments capable of producing images of fluorescent labelled components of cells grown in microtitre plates. These instruments are typically bundled with analysis software capable of defining the relative distribution of several fluorescent markers on a cell by cell basis1,2. As the readers have improved and image acquisition and analysis times have reduced, the potential for screening larger compound libraries has presented itself. High Content Screening (HCS) i.e. the generation of multiparameter data from a single well, has thus become an important tool in the High-Throughput Screening (HTS) laboratory.
The pharmaceutical industry has significantly influenced laboratory automation trends in the past two decades. The need to screen large collections of chemical entities in a short time with minimised consumption of reagents has driven a strong demand of parallelisation, automation, simplification and miniaturisation solutions from the suppliers of instruments, labware and assay technologies. Currently, the levels of automation and miniaturisation seem to have reached a plateau and the new paradigms are flexibility and information content.
High Throughput Screening (HTS) has for many years now been playing a central role in drug discovery efforts to aid the identification of small molecule chemical entities that are capable of modifying the activity of disease relevant targets1. In order to make HTS a viable option to provide appropriate starting points for drug discovery efforts, large libraries of compounds are required that contain diverse chemical space.
Issue 3 2007 / 23 May 2007 / Colleen B. Jonsson, Ph.D., Program Leader, Emerging Infectious Disease Research and E. Lucile White, Manager, High-Throughput Screening Center and Enzymology Laboratory, Southern Research Institute, Birmingham, AL, United States
There are over 300 human viruses that have no treatment, vaccine or antiviral. Unfortunately, only sixty-two drugs are approved by the US Food and Drug Administration (FDA) for the treatment of six different viral illnesses. Of these, 45% are for the treatment of HIV/AIDS. The remaining drugs offer treatments that target hepatitis B and C, herpes, influenza, and respiratory syncytial viruses. Antiviral drugs can play a significant role in the containment of an outbreak of an emerging virus. Vaccination of individuals during an outbreak can also prove effective; however, protection of an individual from the threat may not occur for two or more weeks after the initial vaccination. Hence, only a drug can be offered as a prophylactic treatment of individuals in an endemic area.