The Hit-to-lead Process

Gillespie P, Goodnow RA Jr (2004) The hit-to-lead process in drug discovery. In Doherty A (ed) Annual reports in medicinal chemistry. Elsevier, Oxford, p 293... 

The objective of this volume is to provide an overview of the hit-to-lead process it is not intended to be all inclusive. Furthermore, much of the methodology described here is influenced by the culture of the authors respective institutions. In general, however, lead seeking approaches across industry (and academia) are more similar than they are different and are, for the most part, captured in this volume. 

Goodnow, R.A., Jr, Gillespie, P., Bleicher, K. Chemoinformatic tools for library design and the hit-to-lead process a user s perspective. In Chemoinformatics in Drug Discovery, Oprea, T.I. (ed.) Wiley-VCH, Weinheim, 2004, 381-435. 

Alanine, A., Nettekoven, M., Roberts, E., and Thoma, A.W. Lead generation - enhancing the success of dmg discovery by investing in the hit to lead process. Comb. Chem. High Throughput Screen. 2003, 6, 51-66. 

Chemoinformatic Tools for Library Design and the Hit-to-Lead Process A User s Perspective... 

The goal of the hit-to-lead process is to develop a hit or series of hits to the point where significant resources can be committed for lead optimization. Occasionally, a hit from... 

Our approach to the hit-to-lead process is shown in Figure 15.10. It is shown as a linear process, but several of the steps may require iterations. 

Throughout the period of the hit-to-lead process, additional analogs may be prepared to improve understanding of the SAR of the series to give an impression of whether chemistry space in the series is limited and to show that analogs can be prepared in a timely manner. 

If hits with good properties were selected at the outset, we can hope to arrive at the end of the hit-to-lead process with a series of compounds meeting our lead series criteria, where issues have been flagged and appear tractable. These compounds then provide the launching point for the next phase, lead optimization. 

Wunberg, T., Hendrix, M., Hillisch, A., Lobell, M., Meier, H., Schmeck, C., Wild, H., Hinzen, B. Improving the hit-to-lead process data-driven assessment of drug-like and lead-like screening hits. Drug Discov. Today 2006, 11, 175-80. 

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