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Cited by 347

The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.

MICE Models: Superior to the HERG Model in Predicting Torsade de Pointes

Open access
Kramer, James, Obejero-Paz, Carlos A., Myatt, Glenn, Kuryshev, Yuri A., Bruening-Wright, Andrew, Verducci, Joseph S., Brown, Arthur M.·2013·Scientific Reports
DOI 10.1038/srep02100
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Abstract

Drug-induced block of the cardiac hERG (human Ether-à-go-go-Related Gene) potassium channel delays cardiac repolarization and increases the risk of Torsade de Pointes (TdP), a potentially lethal arrhythmia. A positive hERG assay has been embraced by regulators as a non-clinical predictor of TdP despite a discordance of about 30%. To test whether assaying concomitant block of multiple ion channels (Multiple Ion Channel Effects or MICE) improves predictivity we measured the concentration-responses of hERG, Nav1.5 and Cav1.2 currents for 32 torsadogenic and 23 non-torsadogenic drugs from multiple classes. We used automated gigaseal patch clamp instruments to provide higher throughput along with accuracy and reproducibility. Logistic regression models using the MICE assay showed a significant reduction in false positives (Type 1 errors) and false negatives (Type 2 errors) when compared to the hERG assay. The best MICE model only required a comparison of the blocking potencies between hERG and Cav1.2.

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Metadata

Authors
Kramer, J., Obejero-Paz, C. A., Myatt, G., Kuryshev, Y. A., Bruening-Wright, A., Verducci, J. S., & Brown, A. M.
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2013-07-01
Volume
3
Issue
1
Pages
2100-2100
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep02100
OpenAlex
W2073921281
Cited by
347
References
34
FWCI
17.37
Type
journal article
Language
en
Open access
gold

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