Quantifying Risk of Delayed QT Prolongation of Ipatasertib in Preclinical and Clinical Studies in Cancer Patients.

ABSTRACT: QTc prolongation has been associated with torsades de pointes (TdP) and also with other cardiac diseases. We investigated the effect of ipatasertib, a selective serine/threonine kinase (AKT, protein kinase B) inhibitor, on preclinical models of QTc prolongation as well as across two clinical studies. Preclinical in vitro studies suggested that ipatasertib and its metabolite, M1, were unlikely to inhibit human Ether-à-go-go-Related Gene (hERG) channels at the clinically relevant dose. However, clinical evaluation of ipatasertib and its metabolite in the first-in-human study PAM4743g suggested a mild prolongation of the QTc interval, but the effect was delayed, where the maximum change from baseline QTc seemed to occur 2-4 h after time to maximum drug exposure (T_max). QTc prolonga

SUBMITTER: Poon V 

PROVIDER: S-EPMC12267659 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature