In vitro preclinical lead optimisation technologies (PLOTs) in pharmaceutical development.
The explosion of genuine high throughput technologies has allowed large compound libraries to be screened with ever increasing biological specificity, exacerbating the problem of lead candidate selection for subsequent drug development. To avoid creating a bottleneck, compounds identified from the high throughput screens undergo lead optimisation, a medium-throughput screen which allows ranking in terms of their basic absorption, distribution, metabolism, excretion (ADME) and toxicological properties. The historical role of the preclinical scientist in the drug discovery/development continuum has been to perform ADME and toxicology studies, simply to support the regulatory submission of lead candidates. This situation is, however, changing with the development of preclinical lead optimisation technologies (Approaches to High Throughput Toxicity Screening, London, Atterwill et al., 1999) facilitating the selection of leading candidates, thereby bridging the gap between high throughput efficacy screens and traditional safety assessment programmes.
Atterwill
Christopher K
CK
Huntingdon Life Sciences Ltd, Woolley Road, Alconbury, Cambridgeshire PE28 4HS, UK. sales@ukorg.huntingdon.com
Wing
Mark G
MG
D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015507:Drugs, Investigational / Q000493:pharmacokinetics* / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D007880:Legislation, Drug; D009152:Mutagenicity Tests; D010597:Pharmacogenetics; D013678:Technology, Pharmaceutical / Q000379:methods*; D014116:Toxicology / Q000379:methods*
D015507:Drugs, Investigational