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Bioanalysis
BioTechniques
Future Drug Discovery
Future Medicinal Chemistry
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International Journal of Pharmacokinetics
Pharmaceutical Patent Analyst
Therapeutic Delivery
Perspective

Alternative variables in drug discovery: promises and challenges

    Cele Abad-Zapatero

    * Author for correspondence

    Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, MBRB 1052, MC/870, 900 South Ashland Avenue, Chicago, IL, 60607, USA.

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    Email the corresponding author at caz@uic.edu

    ,
    Edmund J Champness

    Optibrium Ltd, 7221 Cambridge Research Park, Beach Drive, Cambridge, CB25 9TL, UK

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    &
    Matthew D Segall

    Optibrium Ltd, 7221 Cambridge Research Park, Beach Drive, Cambridge, CB25 9TL, UK

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    Published Online:20 Mar 2014https://doi.org/10.4155/fmc.14.16

    Abstract

    A number of alternative variables have appeared in the medicinal chemistry literature trying to provide a more rigorous formulation of the guidelines proposed by Lipinski to exclude chemical entities with poor pharmacokinetic properties early in the discovery process. Typically, these variables combine the affinity towards the target with physicochemical properties of the ligand and are named efficiencies or ligand efficiencies. Several formulations have been defined and used by different laboratories with different degrees of success. A unified formulation, ligand efficiency indices, was proposed that included efficiency in two complementary variables (i.e., size and polarity) to map and monitor the drug-discovery process (AtlasCBS). The use of this formulation in combination with an extended multiparameter optimization is presented, with examples, as a promising methodology to optimize the drug-discovery process in the future. Future perspectives and challenges for this approach are also discussed.

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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