BioCentury
ARTICLE | Distillery Therapeutics

Cardiovascular

March 29, 2017 7:14 PM UTC

In vitro and cell culture studies identified a GRK2-inhibiting analog of Paxil paroxetine that could help treat heart failure. Structure-based design, chemical synthesis and in vitro testing of analogs of the selective serotonin reuptake inhibitor (SSRI) Paxil paroxetine yielded a compound that inhibited the activity of GRK2 -- a gene up-regulated in heart failure -- with an IC50 of 30 nM. In a primary mouse cardiomyocyte-based model of adrenergic receptor β (ADRB) agonist-induced heart failure, the compound increased contractility compared with Paxil. Next steps could include testing the compound in animal models of heart failure...