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Industrial-scale screening accelerates discovery of novel drug combination therapies.

Drug combination therapies are widely recognised as essential therapeutic treatments for chronic conditions ranging from infectious diseases to cancer and HIV/AIDS. Such therapies can enhance a clinical efficacy profile, improve the therapeutic window by reducing the effective clinical dosage and possibly delay the onset of acquired drug resistance.

Highlights from GlobalData’s CRO Benchmark Report. Fall 13

The biopharmaceutical industry is currently facing significant headwinds. The blockbuster era is over, development costs are skyrocketing, uncertainty exists around regulatory and reimbursement, patent cliffs, generic erosion and a sluggish global economy all have industry executives losing sleep at night.

Adoption of high content screening at HTS laboratories.

Over the past five years, a majority of HTS laboratories have adopted high content screening (HCS) in their operations. As HTS laboratories have sought more biologically-relevant assays, cell-based assays and high content screening technologies have become more widespread.

HTS a strategy for drug discovery

Whichever technologies are implemented, high throughput screening is set to become one of the cornerstones of drug discovery, however deciding which strategy to implement will provide many headaches. This article concentrates on screens identifying the interaction of small molecules with protein targets rather than target identification screens.

HTS where next?

After approximately a decade of maturation and a three orders of magnitude increase in capabilities, High Throughput Screening (HTS) is now an established discipline within pharmaceutical discovery. But opposing stresses exist within the screening world the resolution of which will significantly affect the path along which the HTS discipline will develop.

TOXICOGENOMICS insights into the present and future

Adverse drug responses are an important post-marketing public health issue, occurring many times in subsets of treatment populations. Promising new approaches to predicting physiological responses to drugs are focused on genomic responses or toxicogenomics1. This article provides a current perspective on toxicogenomics technologies that are aimed at: 1) providing new tools and systems for more rapid, accurate and complete toxicity assessments in advance of human exposure; 2) enhancing the thoroughness and accuracy of toxicity assessments achievable with currently available test systems, and 3) predictive assessments of individualised risk for developing adverse drug reactions.

ASSAY INTERFERENCE a limiting factor in HTS? Summer 03

With current HTS focused on better quality hits, the necessity to differentiate between true and false results puts increasing emphasis on the robustness of the assay technology.This article explores the common causes of assay interference, the effect they have on the main assay technologies used in HTS today and compares their performance relative to the other attributes that make for a good screen. No single technology is ideal in both respects, but fluorescence lifetime appears to offer some advantage in minimising compound-related interference.

accommodating cells in HTS. Winter 03

High Throughput Screening has become an important and integrated part of drug discovery at most pharmaceutical and many biotechnology companies worldwide, and is now entrenched in the drug discovery process.To produce high quality leads, centralised HTS laboratories are expanding their overall role in drug discovery, and have become more closely aligned with the project teams, therapeutic areas and medicinal chemistry departments. Most notable in this push for higher quality leads is an increasing use of cell-based assays in high throughput mode.

Development of an HTS FabD inhibition assay using a new 384-well filter plate to screen novel antibiotics. Winter 05

Several enzymes are involved in the fatty acid biosynthesis (Fab) system of bacterial organisms. Unlike the mammalian FAS enzyme system in which all the active sites are present in a single, multifunctional protein with several domains1, the multi-enzyme system prevalent among bacteria2 makes these proteins attractive targets for novel antibiotics with little or no cross reactivity to the mammalian enzyme.

Building a uHTS laboratory communications from the frontier. Winter 05

Through sheer commercial need to conduct HTS reliably, rapidly and economically, science and technology have partnered to move laboratories from semi-automated craft guilds to industrialised uHTS research operations. To the benefit of both the pharmaceutical and HTS technology industries, todays researcher, tasked with setting up or revamping an HTS laboratory, is faced with a variety of choices from a wide variety of established vendors

Tracking HTS Assay Development Time: opportunity for improving drug discovery. Summer 10

High throughput screening assays are developed more quickly now due to advances in technology, improved liquid handling and sensitive detection, as well as increased communication between scientists in high throughput labs and therapeutic areas. Increased availability of commercial reagents, target proteins and engineered cell lines will relieve current bottlenecks for further improvement.

HTS Systems: impact of reliability on downtime and drug discovery. Winter 10

This article reports the results of a survey on the reliability of automated HTS assay systems and the effect of reliability on output. Evidence supporting the view that HTS systems have associated with them a high degree of downtime was found and a significant proportion was attributed to poor reliability of hardware, both peripheral and integration components.

Cellular Dopamine and Intracellular Calcium Signaling Using the Next Generation HTS Microplate Reader

Two cell-based signaling assays from Invitrogen, Fluo-4 Direct Calcium Assay and Tango-bla U2OS GPCR Assay, were performed on the PHERAstar FS HTS instrument. The PHERAstar FS has several unique features that enhance the performance of these assays including direct optic bottom reading, high resolution cell layer scanning, injection at the point of measurement and dual emission detection.

Neutron scattering provides unique insights for drug R&D. Fall 10

Drug discovery and development is a long and expensive process. Techniques, such as computer modelling, that make the search for promising candidates easier are usually taken up enthusiastically.

Integrating HTS and fragment-based drug discovery.

High-Throughput Screening and Fragment Based Drug Discovery have been considered as alternative approaches to drug discovery for enzyme targets