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Secondary Pharmacology: Screening and Interpretation of Off-target Activities – Focus on translation

Whitebread, Steven and Dumotier, Berengere and Armstrong, Duncan and Fekete, Alexander and Chen, Shanni and Hartmann, Andreas and Mueller, Patrick and Urban, Laszlo (2016) Secondary Pharmacology: Screening and Interpretation of Off-target Activities – Focus on translation. Drug Discovery Today. ISSN 13596446

Abstract

Secondary pharmacology has become an essential tool for the drug discovery process during the past decade and is used extensively in the pharmaceutical industry for off-target mitigation particularly during the lead optimization phase. This was achieved by increasing the translational value of the approach, based on the recognition of biological target – drug molecule – adverse drug reaction (ADR) associations and integration of the secondary pharmacology data with pharmacokinetic parameters. Accumulation of information obtained from reverse translation of clinical ADRs, from recognition of specific phenotypes of target-based animal models and from hereditary diseases provides increasing regulatory confidence in the target-based approach to side effect prediction and mitigation. Here we review the progress of secondary pharmacology during the past decade, highlight and demonstrate its applications and impact in drug discovery.

Item Type: Article
Date Deposited: 26 Apr 2016 23:45
Last Modified: 04 Jul 2016 23:45
URI: https://oak.novartis.com/id/eprint/28133

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