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Lead Generation - Enhancing the Success of Drug Discovery by Investing in the Hit to Lead Process
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2003
Year
Lead ConversionPharmaceutical ResearchHit IdentificationGreen ChemistryLead IdentificationChemistryLead CandidateMedicinal ChemistryDrug Discovery IndustryDrug DevelopmentPharmacologyDrug RepurposingPharmaceutical IndustryNatural SciencesDiscovery ResearchRational Drug DesignTranslational ResearchMedicineLead GenerationDrug DiscoveryLead Optimization
Drug discovery suffers from low success rates, and failing to make timely, knowledge‑based decisions on lead candidates incurs costly downstream delays, so many companies have formed dedicated hit‑to‑lead groups that rely on clear processes and rigorous quality metrics. This paper highlights the importance of a Lead Generation group and its goal of discovering and refining novel lead series with improved drug‑like properties, surveying the processes and tools that enable these objectives. The group employs productivity‑enhancing integrated technologies and early evaluation of drug‑like properties to achieve a balanced activity‑properties profile before full optimisation, and the article reviews the tools and interactions that drive these gains.
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.