SERCA2a activator 1

SERCA2a activator A is a novel sarco/endoplasmic reticulum Ca2+-dependent ATPase 2a (SERCA2a) activator that activates the Ca2+-dependent ATPase activity of cardiac SR vesicles but not that of skeletal muscle SR vesicles that lack of phospholamban (PLN); binds to PLN (Kd=75 uM), attenuates its inhibition of SERCA2a; enhances systolic and diastolic functions in rat hearts.

Signaling Pathways >> Membrane Transporter/Ion Channel >> Calcium Channel

Research Areas >> Cardiovascular Disease

SERCA2a[1]

SERCA2a activator 1 (Compound A) activates the Ca2+-dependent ATPase activity of cardiac sarcoplasmic reticulum (SR) vesicles but not that of skeletal muscle SR vesicles that lack phospholamban (PLN). The surface plasmon resonance assay reveals a direct interaction between SERCA2a activator 1 and PLN, suggesting that the binding of SERCA2a activator 1 to PLN attenuates its inhibition of SERCA2a, resulting in SERCA2a activation[1]. SERCA2a activator 1 also increases the Ca2+ transients and contraction and relaxation of isolated adult rat cardiomyocytes. In isolated perfused rat hearts, the SERCA2a activator 1 enhances systolic and diastolic functions[1].

SERCA2a activator 1 (Compound A; 30mg/kg; intravenous injection; male Wistar rats) treatment significantly enhances the diastolic function in anesthetized normal rats[1]. Animal Model: Male Wistar rats (7-8 weeks old)[1] Dosage: 30mg/kg Administration: Intravenous injection Result: Significantly enhanced the diastolic function in anesthetized normal rats.

[1]. Kaneko M, et al. A pyridone derivative activates SERCA2a by attenuating the inhibitory effect of phospholamban. Eur J Pharmacol. 2017 Nov 5;814:1-8.