In vitro hERG patch clamp assays have become standard components in cardiac safety evaluation during nonclinical drug development. However, prediction of in vivo effects from in vitro measurements of hERG block may be complicated in the case of drugs that are strongly protein bound. The complication arises from the fact that only the free, unbound drug is active against hERG. Thus, accurate estimation of hERG potency in vitro is performed in the absence of serum protein, unlike the in vivo condition where drugs are present in both free and protein-bound forms.
Conventional manual patch clamp evaluation of hERG potency in the presence of 100% fetal bovine serum (FBS, dialyzed) evaluates the effect of drug-protein binding on hERG inhibition.
hERG Serum Shift Assay Benefits
Measures hERG block in the presence and absence of serum proteins
Conventional manual patch clamp for “gold standard” accuracy