Key result
Preclinical safety margins for hERG IC50 and dog QTc effects strongly predicted clinical QTc prolongation, yielding ROC AUC values of 0.80 and 0.81, respectively.
Why the study?
Does preclinical hERG IC50 and dog QTc data predict clinical QT interval prolongation risk for pharmacological compounds?
Population
24 pharmacological compounds (13 clinical QTc positives; 11 negatives)
Comparison
Preclinical assessment of hERG channel block and… vs Clinical heart rate-corrected QT interval data
Design
Other
Authors
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Safety margins <30-fold from hERG/dog data flag higher clinical QTc risk; leaves open need for integrated risk assessment in early development.
Observational (n=24)
Does preclinical hERG IC50 and dog QTc data predict clinical QT interval prolongation risk for pharmacological compounds?
Effect estimate: AUC 0.81
Preclinical hERG IC50 and dog QTc data show good concordance with clinical QT prolongation risk, supporting the progression of low-potency hERG blockers in early drug discovery.
Pollard et al. (2017) conducted an observational in Drug-induced QT interval prolongation (n=24). Preclinical hERG IC50 and dog QTc data was evaluated on Concordance between preclinical data and clinical QTc prolongation (AUC 0.81). Preclinical safety margins for hERG IC50 and dog QTc effects strongly predicted clinical QTc prolongation, yielding ROC AUC values of 0.80 and 0.81, respectively.
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