HTS and hit finding in academia--from chemical genomics to drug discovery

Abstract

The liaison between academia and the pharmaceutical industry was originally served primarily through the scientific literature and limited, specific industry-academia partnerships. Some of these partnerships have resulted in drugs on the market, such as Vorinostat (Memorial Sloan-Kettering Cancer Centre and Merck) and Tenofovir (University of Leuven; Institute of Organic Chemistry and Biochemistry, Czech Republic; and GlaxoSmithKline), but the timescales from concept to clinic have, in most cases, taken many decades. We now find ourselves in a world in which the edges between these sectors are more blurred and the establishment and acceptance of high-throughput screening alongside the wider concept of 'hit discovery' in academia provides one of the key platforms required to enable this sector to contribute directly to addressing unmet medical need.

Figure 1

Geographical distribution of the majority of existing academic screening centres (data drawn primarily from the SBS Academic Screening Facilities Directory at http://www.sbsonline.org/).

Figure 2

Representation of some key elements underpinning an effective screening facility, including (clockwise, from top left): example of a rectangular design experiment to optimize biochemical assay parameters, as depicted using MODDE V8 software (Umetrics); 2D scatter plot depicted using Vortex software (Dotmatics); plate representation of compound potency depicted using ActivityBase XE software (IDBS); chemical registration view using Register software (Dotmatics); compound storage facilities (REMP); automated liquid handling instrumentation; single-field images of plated cultured embryonic stem cells stained for a pluripotency marker (upper), leishmania promastigotes (left), ribbon diagram of Trypanosoma brucei pteridine reductase (centre), Xenopus XLK2 kidney cell in mitosis (right), electron micrograph of T. brucei (lower); and a bioinformatics array plot of screens (x-axis) against compounds (y-axis) where compound potency is displayed as a colour gradient from red (most active) to green (inactive).

Figure 3

Relative size of compound collections held in 44 of the academic screening facilities (data drawn from the SBS Academic Screening Facilities Directory).