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.
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.
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.
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.
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.
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 domains (1), the multi-enzyme system prevalent among bacteria (2) makes these proteins attractive targets for novel antibiotics with little or no cross reactivity to the mammalian enzyme.
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.
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.
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.