| A quantitative assessment of hERG liability as a function of lipophilicity. | |
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MedLine Citation:
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PMID: 17239590 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The impact of lipophilicity as a factor contributing to hERG potency is assessed for a large dataset of compounds of differing ionisation type. This dataset is derived from compounds tested in the IonWorks-based in vitro electrophysiology hERG assay at AstraZeneca. Using logistic regression, a quantification of the risk associated with increasing lipophilicity is presented. The anticipated differences between acidic, basic and neutral compounds are apparent in the data but lipophilicity is shown to be a stronger driver for hERG potency than might have been expected. Simple rules defining target lipophilicity values for minimizing hERG liability are derived. |
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Authors:
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Michael J Waring; Craig Johnstone |
Publication Detail:
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Type: Journal Article Date: 2006-12-22 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: 17 ISSN: 0960-894X ISO Abbreviation: Bioorg. Med. Chem. Lett. Publication Date: 2007 Mar |
Date Detail:
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Created Date: 2007-02-23 Completed Date: 2007-05-29 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9107377 Medline TA: Bioorg Med Chem Lett Country: England |
Other Details:
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Languages: eng Pagination: 1759-64 Citation Subset: IM |
Affiliation:
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AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. mike.j.waring@astrazeneca.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Algorithms Chemistry, Physical Databases, Factual Ether-A-Go-Go Potassium Channels / drug effects* Humans Lipids / chemistry* Logistic Models Physicochemical Phenomena Potassium Channel Blockers / chemistry*, pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/ERG1 potassium channel; 0/Ether-A-Go-Go Potassium Channels; 0/Lipids; 0/Potassium Channel Blockers |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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