BIX 02565

BIX 02565 is a potent ribosomal S6 kinase 2 (RSK2) inhibitor with IC₅₀ of 1.1 nM. IC50 & Target: IC50: 1.1 nM (RSK2)^[1] In Vitro: BIX 02565, a potent RSK2 inhibitor (IC₅₀=1.1 nM) targets for the treatment of heart failure secondary to myocardial infarction through indirect NHE inhibition^[1]. BIX 02565, a second Rsk inhibitor, protects enzyme active sites from reaction with biotinylated nucleotide acyl phosphates^[2]. In Vivo: In telemetry-instrumented rats, BIX 02565 (30, 100, and 300 mg/kg p.o. QD for 4 days) elicits concentration-dependent decreases in MAP after each dose (to -39±4 mm Hg on day 4 at T_max). BIX 02565 produces concentration-dependent relaxation ex vivo in the phenylephrine-constricted rat aortic ring at concentrations above 0.03 μM with a calculated EC₅₀ of 3.1 μM. Subsequently, BIX 02565 is infused in the anesthetized rat in a low-dose (0.1, 0.3, and 1.0 mg/kg per 20 min) and high-dose (1.0, 3.0, and 10.0 mg/kg per 20 min) series of continuous infusions to test the effect of compound on hemodynamics in vivo^[1].