Medicinal Chemistry Strategies to Minimize Phospholipidosis

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Abstract:

Drug-induced phospholipidosis is characterised by an excessive accumulation of polar phospholipids in cells or tissues. However, from a toxicological perspective the functional consequences of phospholipidosis remain uncertain and a regulatory position unclear. As a consequence, to minimize compound development risk pharmaceutical companies are beginning to proactively address phospholipidosis within drug discovery programs, and implement strategies to identify compounds predicted to show no phospholipidosis. Examples of optimization of compounds to minimize phospholipidosis, and the status of current in silico prediction models, are presented and discussed.

Keywords: Drug-induced phospholipidosis; cationic amphiphilic drugs; in silico models; medicinal chemistry; physicochemical; prediction; strategies; toxicology

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986709788803213

Affiliations: Department of Medicinal Chemistry, Cellzome Ltd, Chesterford Research Park, Little Chesterford, Cambridge, CB10 1XL, UK.

Publication date: August 1, 2009

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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