Biological Activity
bix 02565 is a novel inhibitor of ribosomal s6 kinase 2 with ic50 value of 1 nm [1].ribosomal s6 kinase (rsk) is a na/h exchanger (nhe) -activating factor and is important for ph maintenance during the early phase of cellular stress. while, nhe activation leads to ca2+ overload and cardiac hypertrophy over longer periods [2].bix 02565 is a novel rsk2 inhibitor. also, bix 02565 inhibited adrenergic ɑ1a-, ɑ1b-, ɑ1d-, ɑ2a-, β2- and imidazoline i2 receptors with ic50 values ranging from 0.052 to 1.820 μm. these receptors played important roles in the regulation of vascular tone and cardiac function [2]. also, bix 02565 inhibited lrrk2 and prkd1 with ic50 values of 16 and 35 nm [1].in the rat cv screen, bix 02565 (1, 3 and 10 mg/kg) significantly decreased heart rate (-93 +13 beats/min) and mean arterial pressure (map: to -65 +6 mm hg below baseline). in telemetry-instrumented rats, bix 02565 (30, 100 and 300 mg/kg for 4 days) reduced map (to -39 + 4 mm hg) in a concentration-dependent way [2].
References
[1]. kirrane tm, boyer sj, burke j, et al. indole rsk inhibitors. part 2: optimization of cell potency and kinase selectivity. bioorg med chem lett, 2012, 22(1): 738-742.
[2]. fryer rm, muthukumarana a, chen rr, et al. mitigation of off-target adrenergic binding and effects on cardiovascular function in the discovery of novel ribosomal s6 kinase 2 inhibitors. j pharmacol exp ther, 2012, 340(3): 492-500.
