Abstract
Improving on the poor success rates in the drug discovery industry requires that knowledge-based decisions are made to advance or stop a lead candidate as early as possible in the discovery process. Failure to make such timely decisions on the rigorous selection of lead candidates has costly time and resource implications in downstream drug development. To meet this challenge dedicated ‘hit to lead’ groups have recently been established in many major pharmaceutical companies, and a key to the success of such groups is establishing a clear consistent process and rigorous metrics for lead quality. The importance of such a “Lead Generation” group within the drug discovery process will be highlighted with the aim of placing a greater level of emphasis in discovering and refining novel lead series with enhanced drug-like properties. This activity is facilitated by the application of productivity enhancing, integrated technologies coupled with the early evaluation of drug-like properties in the lead refinement process to ensure that a balanced activity - properties profile can be attained before committing to a full lead optimisation program. This article will survey the processes and tools employed in the hit to lead process in such a “Lead Generation” group in order to achieve these objectives, emphasising the possible gains in productivity through close, early interactions between chemistry and other expert groups.
Keywords: hit to lead, hit validation, lead generation, lead optimisation, lead series identification, medicinal chemistry, multi-dimensional optimisation, early adme
Combinatorial Chemistry & High Throughput Screening
Title: Lead Generation - Enhancing the Success of Drug Discovery by Investing in the Hit to Lead Process
Volume: 6 Issue: 1
Author(s): Alexander Alanine, Matthias Nettekoven, Edward Roberts and Andrew W. Thomas
Affiliation:
Keywords: hit to lead, hit validation, lead generation, lead optimisation, lead series identification, medicinal chemistry, multi-dimensional optimisation, early adme
Abstract: Improving on the poor success rates in the drug discovery industry requires that knowledge-based decisions are made to advance or stop a lead candidate as early as possible in the discovery process. Failure to make such timely decisions on the rigorous selection of lead candidates has costly time and resource implications in downstream drug development. To meet this challenge dedicated ‘hit to lead’ groups have recently been established in many major pharmaceutical companies, and a key to the success of such groups is establishing a clear consistent process and rigorous metrics for lead quality. The importance of such a “Lead Generation” group within the drug discovery process will be highlighted with the aim of placing a greater level of emphasis in discovering and refining novel lead series with enhanced drug-like properties. This activity is facilitated by the application of productivity enhancing, integrated technologies coupled with the early evaluation of drug-like properties in the lead refinement process to ensure that a balanced activity - properties profile can be attained before committing to a full lead optimisation program. This article will survey the processes and tools employed in the hit to lead process in such a “Lead Generation” group in order to achieve these objectives, emphasising the possible gains in productivity through close, early interactions between chemistry and other expert groups.
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Cite this article as:
Alanine Alexander, Nettekoven Matthias, Roberts Edward and Thomas W. Andrew, Lead Generation - Enhancing the Success of Drug Discovery by Investing in the Hit to Lead Process, Combinatorial Chemistry & High Throughput Screening 2003; 6 (1) . https://dx.doi.org/10.2174/1386207033329823
DOI https://dx.doi.org/10.2174/1386207033329823 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
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