Encyclopedia of Cancer

Living Edition
| Editors: Manfred Schwab

Lead Optimization

  • Mark R. Player
Living reference work entry
DOI: https://doi.org/10.1007/978-3-642-27841-9_3298-3


The synthetic chemical modification of a biologically active molecule to address pharmacokinetic, pharmacodynamic, and toxicologic issues in order to enable its clinical utility.


Drug discovery activities that occur prior to lead optimization, such as the choice of target, assay development, high-throughput screening, and early molecular optimization and testing, are typically referred to as lead generation. Leads typically have been somewhat optimized for their molecular properties (solubility, removal of covalent modifiers, chemical stability), have been subjected to in vitro assays to predict their pharmacokinetic properties (Caco-2 flux, liver microsomal stability, protein binding, inhibitory activity toward cytochrome P450 isoenzymes(CYP450s)), possess reasonable in vitro and cellular potencies toward the molecular target, and have been subjected to some selectivity measurements (kinase selectivity screen and a broad receptor/transporter selectivity...


Oral Bioavailability Reactive Metabolite Lead Optimization Idiosyncratic Drug Reaction Flavin Monooxygenases 
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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Johnson & Johnson Pharmaceutical Research & DevelopmentSpring HouseUSA