Avoiding Missed Opportunities by Analyzing the Sensitivity of Our Decisions

Drug discovery is a multiparameter optimization process in which the goal of a project is to identify compounds that meet multiple property criteria required to achieve a therapeutic objective. However, once a profile of property criteria has been chosen, the impact of these criteria on the decision...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2016-05, Vol.59 (9), p.4267-4277
Main Authors: Segall, Matthew D, Yusof, Iskander, Champness, Edmund J
Format: Article
Language:English
Subjects:
Drug Discovery
Probability
Uncertainty
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Summary:Drug discovery is a multiparameter optimization process in which the goal of a project is to identify compounds that meet multiple property criteria required to achieve a therapeutic objective. However, once a profile of property criteria has been chosen, the impact of these criteria on the decisions made regarding progression of compounds or chemical series should be carefully considered. In some cases the decision is very sensitive to a specific property criterion, and such a criterion may artificially distort the direction of the project; any uncertainty in the “correct” value or the importance of this criterion may lead to valuable opportunities being missed. In this paper, we describe a method for analyzing the sensitivity of the prioritization of compounds to a multiparameter profile of property criteria. We show how the results can be easily interpreted and illustrate how this analysis can highlight new avenues for exploration.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.5b01921