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 accessAbstract
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
- Published
- 2013-07-01
- Volume
- 3
- Issue
- 1
- Pages
- 2100-2100
- ISSN
- 2045-2322 (ISSN-L)
- OpenAlex
- W2073921281
- Cited by
- 347
- References
- 34
- FWCI
- 17.37
- Type
- journal article
- Language
- en
- Open access
- gold
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- Kramer, J., Obejero-Paz, C. A., Myatt, G., Kuryshev, Y. A., Bruening-Wright, A., Verducci, J. S., & Brown, A. M. (2013). MICE Models: Superior to the HERG Model in Predicting Torsade de Pointes. Scientific Reports. https://doi.org/10.1038/srep02100
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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