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Alternatives to Laboratory Animals - ATLA

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Comment: In Vitro Preclinical Lead Optimisation Technologies (PLOTs) in Pharmaceutical Development

Christopher K. Atterwill and Mark G. Wing

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 by employing medium-throughput screens which permit 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 facilitating the selection of leading candidates, thereby bridging the gap between high throughput efficacy screens and conventional safety assessment programmes.