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J Pharmacol Toxicol Methods. 2017 Sep;87:108-126. doi: 10.1016/j.vascn.2017.02.020. Epub 2017 Feb 16.

Potential functional and pathological side effects related to off-target pharmacological activity.

Author information

1
AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA. Electronic address: james.j.lynch@abbvie.com.
2
AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA.

Abstract

Most pharmaceutical companies test their discovery-stage proprietary molecules in a battery of in vitro pharmacology assays to try to determine off-target interactions. During all phases of drug discovery and development, various questions arise regarding potential side effects associated with such off-target pharmacological activity. Here we present a scientific literature curation effort undertaken to determine and summarize the most likely functional and pathological outcomes associated with interactions at 70 receptors, enzymes, ion channels and transporters with established links to adverse effects. To that end, the scientific literature was reviewed using an on-line database, and the most commonly reported effects were summarized in tabular format. The resultant table should serve as a practical guide for research scientists and clinical investigators for the prediction and interpretation of adverse side effects associated with molecules interacting with components of this screening battery.

KEYWORDS:

Drug development; Drug discovery; Enzyme; Ion channel; Off-target; Receptor; Safety pharmacology; Side effect; Toxicology; Transporter

PMID:
28216264
DOI:
10.1016/j.vascn.2017.02.020
[Indexed for MEDLINE]

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