GSK854

GSK854 is a TNNI3K inhibitor. GSK854 binds to the DFG-out conformation of the ATP-binding site and forms hydrogen bonds with the hinge and gatekeeper. GSK854 reduces mitochondrial superoxide production, ROS, and p38 MAPK activation, and protects mitochondrial membrane potential and cardiac function. GSK854 can be used in research on ischemia/reperfusion cardiac injury, heart failure, acute coronary syndrome, and ischemic heart disease^{[1][2][3][4][5][6]}. In Vitro:GSK854 is a potent inhibitor of TNNI3K with a biochemical IC₅₀ of ≤10 nM^[1].
GSK854 demonstrates potent cellular activity against TNNI3K with an IC₅₀ of 8 nM and an AMP of 74 nm/s^[1].
GSK854 is a highly potent inhibitor of TNNI3K with an IC₅₀ of ≤10 nM and demonstrates significant selectivity over B-Raf and EGFR^[2].
GSK854 rescues ROS elevation in NRVMs but does not act as a non-specific ROS scavenger^[3]. In Vivo:GSK854 (2.75 mg/kg; i.p.; single dose at reperfusion) administered at reperfusion significantly reduces infarct size, superoxide production, and p38 activation in wild-type C57BL/6 mice after myocardial ischemia-reperfusion injury^[3].
GSK854 (2.75 mg/kg; i.p.; at reperfusion and again 6 hours after reperfusion, followed by ad libitum chow for 6 weeks) administered at reperfusion and via chow for 6 weeks preserves cardiac function, limits adverse ventricular remodeling, reduces hypertrophy, and decreases fibrosis in a mouse model of reperfused myocardial infarction^[3].