The 90 kDa ribosomal S6 kinases (RSKs) are a group of serine/threonine kinases involved in diverse cellular processes, including growth, survival, and motility. Phosphorylation of the sodium-hydrogen exchanger (NHE) in cardiac tissue by RSK has been shown to activate NHE during cellular stresses, such as myocardial infarction, as a mechanism to maintain pH. BIX 02565 is a RSK2 inhibitor with an IC50 value of 1.1 nM. It also demonstrates off-target binding at multiple adrenergic receptor subtypes that are important for vascular tone and cardiac function (IC50s = 0.052-1.820 μM for adrenergic ɑ1A, ɑ1B, ɑ1D, ɑ2A, β2, and imidazoline I2 receptors. BIX 02565 can also inhibit LRRK2 and PRKD1 with IC50 values of 16 and 35 nM, respectively). In rats, BIX 02565 at 1, 3, and 10 mg/kg was shown to significantly decrease heart rate and mean arterial pressure.
