Ligand efficiency measures

Stevan W. Djuric, Irini Akritopoulou-Zanze, Philip B. Cox and Scott Galasinski 

3 Assessing risk—from Rule of Five to Rule of 3/7S 421 

Medicinal Chemistry Technologies, Advanced Technologies, Abbott Laboratories, Abbott Park, IL 60064, USA 

Annual Reports in Medicinal Chemistry, Volume 45 ISSN 0065-7743, DOI 10.1016/S0065-7743(10)45025-3 

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As an example of the latter in drug design, we show the combined use of a size-based and a lipophilicity-based ligand efficiency measure in a project situation. 

Nissink JWM (2009) Simple size-independent measure of ligand efficiency. J Chem Inf Model 49 1617-1622... 

The modified ligand efficiency will have a greater preference for smaller fragments, thereby rendering it inefficient as a measure for prioritizing compounds for lead development. To circumvent the observed size dependency on LE, Brandt... 

Although this measure of ligand efficiency is the most widely used, it has been proposed that the LE index could be replaced by size-independent indices like the fit quality score (FQ) [19] or the percentage LE [20], which allow the comparison of fragments irrespective of their molecular weight. Many other related indices (listed in Table 1) have also been proposed recently to take into account properties other than molecular weight in the fragment-to-lead optimization, such as polar surface area or lipophilicity [20]. 

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