Ibrutinib-Mediated Atrial Fibrillation Attributable to Inhibition of C-Terminal Src Kinase.

ABSTRACT:

Background

Ibrutinib is a Bruton tyrosine kinase inhibitor with remarkable efficacy against B-cell cancers. Ibrutinib also increases the risk of atrial fibrillation (AF), which remains poorly understood.

Methods

We performed electrophysiology studies on mice treated with ibrutinib to assess inducibility of AF. Chemoproteomic analysis of cardiac lysates identified candidate ibrutinib targets, which were further evaluated in genetic mouse models and additional pharmacological experiments. The pharmacovigilance database, VigiBase, was queried to determine whether drug inhibition of an identified candidate kinase was associated with increased reporting of AF.

Results

We demonstrate that treatment of mice with ibrutinib for 4 weeks results in inducible AF, left atrial enla

SUBMITTER: Xiao L 

PROVIDER: S-EPMC9661397 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature