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.
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.
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.
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 toxicogenomics (1).
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 (HTS) 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.