Hit-to-Lead
The hit to lead phase is a critical phase of drug discovery programs. The first set of compounds, or hits, that demonstrate promising activity against a target of interest are further characterized. Through limited medicinal chemistry efforts, the aim is to turn these hits into leads: compounds that we believe can be optimized into drug candidates.
- How do we select the most promising chemical matter from all hit series?
- How do we start optimizing a scaffold?
- How do we make sure the optimization is progressing as it should?
- When do we know when to stop working on a chemical series?
Following hit identification, learn how to enhance biological activity and improve compound properties by reviewing our Hit Generation Best Practices. To support this optimization phase, it’s critical to employ reliable chemical tools as described in our Validating Chemical Probes guidelines, and consider the use of innovative modalities like PROTACs for selective protein degradation.
Please cite the EFMC Best Practices in Medicinal Chemistry WG work as following (please include both):
- Quancard, J., Vulpetti, A., Bach, A., Cox, B., Guéret, S. M., Hartung, I. V., Koolman, H. F., Laufer, S., Lepri, S., Messinger, J., Ritter, K., Sbardella, G., Unzue Lopez, A., Willwacher, M. K., & Young, R. J. (2025). The European Federation for Medicinal Chemistry and Chemical Biology (EFMC) Best Practices: Hit to Lead. ChemMedChem, 2025, e202400931. https://doi.org/10.1002/cmdc.202400931
- The material (webinars, slide decks and case studies) is freely accessible for personal use or for use in further training or teaching material from the EFMC website: https://www.efmc.info/hit-to-lead