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.

ISIDA Property‐Labelled Fragment Descriptors

“…[1][2][3][4] Standard methods include quantitative structure-activity relationships (QSAR) [5][6][7][8] and similarity-based virtual screening. [9][10][11][12] However, although an enormous amount of descriptors [13][14][15][16] are available and data mining [17][18][19] methods are implemented for chemoinformatics tasks, significant differences of activity still arise among molecules perceived as similar by the computational tool (activity cliffs).…”

The pharmaceutical industry and natural products: historical status and new trends

“…Undoubtedly, in industry HTS automation is the likely means of targeting bioactivity whilst in many academic institutions due to limitations in funding, HTS is not generally used inhouse and often requires outsourcing with limitations to the number of possible biological screens. Of course, utilizing modern techniques of HTS at least in theory, can lead to the identification of NCEs and hits, but the serendipity behind analyzing a less uncommon terrestrial or marine organism should not be overlooked (Michael et al 2008;Frearson and Collie 2009;Macarrón et al 2011).…”

Assay Design for High‐Throughput Screening

“…Further, a number of recent FDA-approved drugs originated from an HTS, such as Maraviroc (Pfizer), Dasatinib (Bristol-Myers Squibb), and Eltrombopag (GlaxoSmithKline) [3,4]. Growing interest in HTS has spread to the academic sector in recent years [5,6], among the most notable being funding by the U.S. National Institute of Health (NIH) of the Molecular Libraries Screening Center Network as a pilot phase in 2004 and the Molecular Libraries Production Center Network (MLPCN) as a second phase in 2008. The goal of this effort was to support HTS and structureactivity relationship (SAR) studies in the public sector for the development of small-molecule probes (http://mli.nih.gov/mli/mlpcn/).…”