Screening: In-Depth Focus 2014

• Assay techniques for the identification of compounds that protect against free radicals
  Peter McDonald and Anuradha Roy, University of Kansas
  The biology and the chemistry of free radical generation and their effects on cell physiology in homeostasis and disease have been reviewed extensively. Aerobic reactions in mitochondria, endoplasmic reticulum and peroxisomes result in accumulation of oxygen-derived reactive molecules and free radicals as byproducts. ROS (Reactive Oxygen Species) are also generated by radiation and from the metabolism of various drugs, oxidation of phenols or aromatic amines and compound autoxidation catalysed by transition metal ions. Being short-lived and unstable, the reactive oxygen species manifest their effects by readily reacting with other cellular chemical species..
• Hit validation and optimisation in earlystage drug discovery
  Michelle Arkin and Jeff Neitz, Small Molecule Discovery Center, UCSF
  In drug discovery, the process of developing an initial ‘hit’ compound into a bona fide lead is idiosyncratic. This article describes the general process for this ‘hit-to-lead’ phase, starting from validation of hits arising from screening. The decision workflow for compound optimisation will depend on the target profile for the eventual drug. It is important to select hits based on biological mechanism and physicochemical properties…
• The role and future of sandwich immunoassays in phenotypic screening
  Steve Ludbrook, Rob Jepras and Gareth Wayne, GlaxoSmithKline
  Sandwich immunoassays are in widespread use across research and clinical applications as gold-standard methods for the accurate detection of protein analytes. With the renaissance in phenotypic assay approaches for pre-clinical drug discovery, recent advances in higher throughput aligned sandwich immunoassay technologies are enabling this method to be utilised earlier in the drug discovery process, enabling clinically relevant assays to be interrogated up to high throughput screening scales. Rapid progress in miniaturisation approaches should maintain and increase the use of such assays at the front end of drug discovery approaches…