A theoretical entropy score as a single value to express inhibitor selectivity

Background: Designing maximally selective ligands that act on individual targets is the dominant paradigm in drug discovery. Poor selectivity can underlie toxicity and side effects in the clinic, and for this reason compound selectivity is increasingly monitored from very early on in the drug discovery process. To make sense of large amounts of profiling data, and to determine when a compound is sufficiently selective, there is a need for a proper quantitative measure of selectivity. Results: Here we propose a new theoretical entropy score that can be calculated from a set of IC50 data. In contrast to previous measures such as the ‘selectivity score’, Gini score, or partition index, the entropy score is nonarbitary, fully exploits IC50 data, and is not dependent on a reference enzyme. In addition, the entropy score gives the most robust values with data from different sources, because it is less sensitive to errors. We apply the new score to kinase and nuclear receptor profiling d...

• Type: Journal
• Year: 2011
• Where: BMCBI
• Authors: Joost C. M. Uitdehaag, Guido J. R. Zaman
• Keywords: Artificial Intelligence, BMCBI 2011, Drug Discovery, Entropy Score, Theoretical Entropy Score