Background:

SKA-31 is a potent potassium channel activator with EC50s of 260 nM, 1.9 μM, 2.9 μM, and 2.9 μM for KCa3.1, KCa2.2, KCa2.1 and KCa2.3, respectively. SKA-31 potentiates endothelium-derived hyperpolarizing factor response and lowers blood pressure[1].

SKA-31 activates KCa2/3 channels more potently than PK 26124, and is more selective over other Ion channels[1]. SKA-31 reduces cell viability with IC50s of 5.3 μM , 46.9 μM in HCT-116 cells and HCT-8 cells, respectively[2].SKA-31 (5.3 μM; 0-96 hours) reduces HCT-116 cells proliferation when added at time zero at 5.3 μM[2].SKA-31 triggers apoptosis in HCT-116 cells at 5 μM, and the effect is smaller in HCT-8 cells at 45 μM[2].SKA-31 increases the percentage of cells in G0/G1 phase in HCT-116 and HCT-8 cell lines at 5 μM and 45 μM, respectively[2].SKA-31 further activates Caspase 3 and reduces Akt phosphorylation induced by CDDP[2].SKA-31 has a synergic effect with CDDP also on the inhibition of HCT-116 cell proliferation[2].

SKA-31 is not acutely toxic and has good pharmacokinetic properties[1].SKA-31 potentiates native KCa3.1 and KCa2.3 in murine carotid endothelium with EC50 values of 225 nM and 1.6 μM for KCa3.1 and KCa2.3, respectively[1].SKA-31 stimulates KCa3.1 and KCa2.3 in vascular endothelial cells and increases acetylcholine-induced endothelium-derived hyperpolarizing factor (EDHF) -mediated vasodilation[1].SKA-31 potentiates EDHF-type vasodilations and lowers blood pressure in mice. Injections of SKA-31 (1-30 mg/kg; i.p.) lower MAP over 24 hours in normotensive wild-type mice but not in KCa3.1(-/-) mice (-/-)[1].

参考文献:
[1]. Sankaranarayanan A, et al. Naphtho[1,2-d]thiazol-2-ylamine (SKA-31), a new activator of KCa2 and KCa3.1 potassium channels, potentiates the endothelium-derived hyperpolarizing factor response and lowers blood pressure. Mol Pharmacol. 2009 Feb;75(2):281-95.
[2]. Serena Pillozzi, et al. The combined activation of KCa3.1 and inhibition of Kv11.1/hERG1 currents contribute to overcome CDDP resistance in colorectal cancer cells. Br J Cancer. 2018 Jan; 118(2): 200–212.