Abstract
Based on analyses of existing small organic drug molecules, a set of “rules-of-thumb” have been devised to assess the likeness of a small molecule under study to those existing drugs in terms of physicochemical and topological properties. These rules can be used to estimate the likelihood of a small molecule to possess the desired efficacy, pharmacokinetic/pharmacodynamic properties, and toxicity profiles to eventually become a drug, and therefore, whether it justifies further experimental work and development. These rules are particularly useful when selecting a chemical starting point for a given project or choosing a chemical series to focus when multiple series are available. Caution should be paid, however, not to overly rely on these rules for decision-making, since these rules are restricted by knowledge of existing drugs. Novel chemotypes and/or targets may be exceptions.
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Zhang, MQ. (2012). Working with Small Molecules: Rules-of-Thumb of “Drug Likeness”. In: Drewes, G., Bantscheff, M. (eds) Chemical Proteomics. Methods in Molecular Biology, vol 803. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-364-6_20
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