SKA-31 (Naphtho[1,2-d]thiazol-2-ylamine) is an activator of KCa3.1 and KCa2 channels (EC50s: 260, 2900, 2900 nM for KCa3.1, KCa2.1 and KCa2.2 respectively).

KCa2.1:2900 nM, KCa3.1:260 nM, KCa2.2:2900 nM

SKA-31能夠激活KCa2.1，其EC(50)值為2.9 microM；KCa2.2的EC(50)值為1.9 microM；KCa2.3的EC(50)值為2.9 microM；以及KCa3.1的EC(50)值為260 nM。SKA-31在小鼠内皮细胞中激活了天然的KCa2.3和KCa3.1通道[1]。SKA-31 (1 μM)能夠激活KCa3.1以及KCa2.3通道，并在野生型CAEC中引起膜超极化（ΔMP -45 mV）。SKA-31（200 nM、500 nM）顯著增强了野生型中EDHF引起的血管舒張[2]。

给予10和30 mg/kg的SKA-31可以分别将正常血压小鼠的平均动脉血压降低4和6 mm Hg，并且在由血管紧张素II引起的高血压中可以降低12 mm Hg [2]。SKA-31 (10 μM) 在阴囊的微血管及中脑动脉中抑制肌肉舒张力分别高达80%和约65%，两种血管的IC50值均约为2 μM [3]。

Jurkat E61 and MEL cells were seeded at 10^5 cells/ml in 12-well plates. SKA-31 was added at concentrations of 10 and 100 μM in a final DMSO concentration of 0.1%, which was found not to affect cell viability. After 48 h, the cells in each well were well mixed and resuspended, and the number of trypan blue-positive cells in three aliquots from each well was determined under a light microscope. The test was repeated twice [1].

For intravenous injection, SKA-31 was dissolved at 10 mg/ml in a mixture of 10% Cremophor EL and 90% saline and injected at 10 mg/kg. For intraperitoneal application, SKA-31 was dissolved at 10 mg/ml in Miglyol 812 neutral oil (caprylic/capric triglyceride). After tail vein injection of the aqueous solution or intraperitoneal administration of the oily solution, approximately 200 μl of blood was collected from the tail into EDTA blood sample collection tubes at various time points. For very early time points (3, 5, and 10 min) after intravenous administration, blood samples were obtained by cardiac puncture under deep isoflurane anesthesia. Plasma was separated by centrifugation and stored at -80°C pending analysis. After determining that SKA-31 plasma concentrations peaked 2 h after application (10 mg/kg i.p.), we took blood samples under deep isoflurane anesthesia by cardiac puncture from a group of three rats before sacrificing the animals to remove brain, heart, liver, spleen, and fat. Tissue samples were homogenized in 1 ml of H2O with a homogenizer, and the protein was precipitated with 1 ml of acetonitrile. The samples were then centrifuged at 3000 rpm, and supernatants were concentrated to 1 ml. Plasma and homogenized tissue samples were purified using C18 solid-phase extraction cartridges. Elution fractions corresponding to SKA-31 were evaporated to dryness under nitrogen and dissolved in acetonitrile [1].