SKA 31Activator of KCa3.1 and KCa2 channels CAS# 40172-65-4 |
2D Structure
- Atrasentan
Catalog No.:BCC1379
CAS No.:173937-91-2
- Zibotentan (ZD4054)
Catalog No.:BCC2524
CAS No.:186497-07-4
- Atrasentan hydrochloride
Catalog No.:BCC1380
CAS No.:195733-43-8
- Avosentan
Catalog No.:BCC1387
CAS No.:290815-26-8
- Macitentan
Catalog No.:BCC1142
CAS No.:441798-33-0
Quality Control & MSDS
3D structure
Package In Stock
Number of papers citing our products
Cas No. | 40172-65-4 | SDF | Download SDF |
PubChem ID | 94880 | Appearance | Powder |
Formula | C11H8N2S | M.Wt | 200.26 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | DMSO : 150 mg/mL (749.03 mM; Need ultrasonic) | ||
Chemical Name | benzo[e][1,3]benzothiazol-2-amine | ||
SMILES | C1=CC=C2C(=C1)C=CC3=C2N=C(S3)N | ||
Standard InChIKey | FECQXVPRUCCUIL-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C11H8N2S/c12-11-13-10-8-4-2-1-3-7(8)5-6-9(10)14-11/h1-6H,(H2,12,13) | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | Activator of KCa3.1 and KCa2 channels (EC50 values are 260, 2900, 2900 nM for KCa3.1, KCa2.1 and KCa2.2 respectively). Potentiates acetylcholine-induced EDHF-type dilations of mouse carotid arteries and lowers blood pressure in normotensive and hypertensive mice. |
SKA 31 Dilution Calculator
SKA 31 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 4.9935 mL | 24.9675 mL | 49.9351 mL | 99.8702 mL | 124.8377 mL |
5 mM | 0.9987 mL | 4.9935 mL | 9.987 mL | 19.974 mL | 24.9675 mL |
10 mM | 0.4994 mL | 2.4968 mL | 4.9935 mL | 9.987 mL | 12.4838 mL |
50 mM | 0.0999 mL | 0.4994 mL | 0.9987 mL | 1.9974 mL | 2.4968 mL |
100 mM | 0.0499 mL | 0.2497 mL | 0.4994 mL | 0.9987 mL | 1.2484 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
- Boc-N-Me-Phe.DCHA
Catalog No.:BCC3348
CAS No.:40163-88-0
- Erucifoline
Catalog No.:BCN2081
CAS No.:40158-95-0
- H-Arg-pNA.2HCl
Catalog No.:BCC2858
CAS No.:40127-11-5
- Ceftaroline fosamil
Catalog No.:BCC5266
CAS No.:400827-46-5
- 20-Hydroxyganoderic acid G
Catalog No.:BCN8231
CAS No.:400604-12-8
- N6-Benzoyladenine
Catalog No.:BCC9075
CAS No.:4005-49-6
- SU 3327
Catalog No.:BCC7725
CAS No.:40045-50-9
- Syringetin-3-O-glucoside
Catalog No.:BCN2610
CAS No.:40039-49-4
- 24, 25-Dihydroxy VD3
Catalog No.:BCC1303
CAS No.:40013-87-4
- H-Thr-OMe.HCl
Catalog No.:BCC3104
CAS No.:39994-75-7
- Laricitrin 3-O-glucoside
Catalog No.:BCN8149
CAS No.:39986-90-8
- p-Hydroxy-5,6-dehydrokawain
Catalog No.:BCN3597
CAS No.:39986-86-2
- Andarine
Catalog No.:BCC1168
CAS No.:401900-40-1
- Fmoc-β-homo-Arg(Pbf)-OH
Catalog No.:BCC2649
CAS No.:401915-53-5
- Fmoc-β-Homo-Gln(Trt)-OH
Catalog No.:BCC2647
CAS No.:401915-55-7
- H-Orn-OMe.2HCl
Catalog No.:BCC3001
CAS No.:40216-82-8
- H-Hyp-OMe.HCl
Catalog No.:BCC3248
CAS No.:40216-83-9
- 5-O-Feruloylquinic acid
Catalog No.:BCN3788
CAS No.:40242-06-6
- Glycitin
Catalog No.:BCN5895
CAS No.:40246-10-4
- ONO-AE3-208
Catalog No.:BCC1822
CAS No.:402473-54-5
- Acetylcimigenol 3-O-alpha-L-arabinopyranside
Catalog No.:BCN1447
CAS No.:402513-88-6
- DMeOB
Catalog No.:BCC7213
CAS No.:40252-74-2
- NSC 693868
Catalog No.:BCC7208
CAS No.:40254-90-8
- Firategrast
Catalog No.:BCC1575
CAS No.:402567-16-2
Inhibition of Myogenic Tone in Rat Cremaster and Cerebral Arteries by SKA-31, an Activator of Endothelial KCa2.3 and KCa3.1 Channels.[Pubmed:25815673]
J Cardiovasc Pharmacol. 2015 Jul;66(1):118-27.
Endothelial KCa2.3 and KCa3.1 channels contribute to the regulation of myogenic tone in resistance arteries by Ca(2+)-mobilizing vasodilatory hormones. To define further the functional role of these channels in distinct vascular beds, we have examined the vasodilatory actions of the KCa channel activator SKA-31 in myogenically active rat cremaster and middle cerebral arteries. Vessels pressurized to 70 mm Hg constricted by 80-100 mum (ie, 25%-45% of maximal diameter). SKA-31 (10 muM) inhibited myogenic tone by 80% in cremaster and approximately 65% in middle cerebral arteries, with IC50 values of approximately 2 muM in both vessels. These vasodilatory effects were largely prevented by the KCa2.3 blocker UCL1684 and the KCa3.1 blocker TRAM-34 and abolished by endothelial denudation. Preincubation with N(G) nitro L-arginine methyl ester (L-NAME, 0.1 mM) did not affect the inhibitory response to SKA-31, but attenuated the ACh-evoked dilation by approximately 45%. Penitrem-A, a blocker of BK(Ca) channels, did not alter SKA-31 evoked vasodilation but did reduce the inhibition of myogenic tone by ACh, the BKCa channel activator NS1619, and sodium nitroprusside. Collectively, these data demonstrate that SKA-31 produces robust inhibition of myogenic tone in resistance arteries isolated from distinct vascular beds in an endothelium-dependent manner.
SK channel-selective opening by SKA-31 induces hyperpolarization and decreases contractility in human urinary bladder smooth muscle.[Pubmed:23174857]
Am J Physiol Regul Integr Comp Physiol. 2013 Jan 15;304(2):R155-63.
Overactive bladder (OAB) is often associated with increased involuntary detrusor smooth muscle (DSM) contractions during the bladder-filling phase. To develop novel therapies for OAB, it is critical to better understand the mechanisms that control DSM excitability and contractility. Recent studies showed that small-conductance Ca(2+)-activated K(+) (SK) channels, SK3 channels, in particular, regulate human DSM function. However, the concept that SK channel-selective pharmacological activation can decrease the excitability and contractility directly in human DSM needs further exploration. Here, we studied the effect of the novel and potent SK channel activator, SKA-31 (or naphtho [1,2-d]thiazol-2-ylamine), on human DSM excitability and contractility at the cellular and tissue level. We used isometric tension recordings on human DSM-isolated strips and the perforated patch-clamp technique on freshly isolated native human DSM cells. SKA-31 significantly decreased spontaneous phasic contractions of DSM-isolated strips. In the presence of the SK channel blocker, apamin, the inhibitory effects of SKA-31 on the DSM spontaneous phasic contractions were significantly reduced. SKA-31 decreased the carbachol- and KCl-induced contractions in human DSM strips. Electrical field stimulation-induced contractions were significantly attenuated in the presence of SKA-31 at all stimulation frequencies (0.5-50 Hz). SKA-31 hyperpolarized the resting membrane potential of human DSM cells. Apamin abolished the hyperpolarizing effect of SKA-31, indicating the involvement of SK channel activation. These results support the concept that pharmacological activation of SK channels with selective openers may represent an attractive new pharmacological approach for decreasing DSM excitability and contractility, thus controlling OAB.
Activation of KCa3.1 by SKA-31 induces arteriolar dilatation and lowers blood pressure in normo- and hypertensive connexin40-deficient mice.[Pubmed:23734697]
Br J Pharmacol. 2013 Sep;170(2):293-303.
BACKGROUND AND PURPOSE: The calcium-activated potassium channel KCa3.1 is expressed in the vascular endothelium where its activation causes endothelial hyperpolarization and initiates endothelium-derived hyperpolarization (EDH)-dependent dilatation. Here, we investigated whether pharmacological activation of KCa3.1 dilates skeletal muscle arterioles and whether myoendothelial gap junctions formed by connexin40 (Cx40) are required for EDH-type dilatations and pressure depressor responses in vivo. EXPERIMENTAL APPROACH: We performed intravital microscopy in the cremaster muscle microcirculation and blood pressure telemetry in Cx40-deficient mice. KEY RESULTS: In wild-type mice, the KCa3.1-activator SKA-31 induced pronounced concentration-dependent arteriolar EDH-type dilatations, amounting to approximately 40% of maximal dilatation, and enhanced the effects of ACh. These responses were absent in mice devoid of KCa3.1 channels. In contrast, SKA-31-induced dilatations were not attenuated in mice with endothelial cells deficient in Cx40 (Cx40(fl/fl):Tie2-Cre). In isolated endothelial cell clusters, SKA-31 induced hyperpolarizations of similar magnitudes (by approximately 38 mV) in Cx40(fl/fl):Tie2-Cre, ubiquitous Cx40-deficient mice (Cx40(-/-)) and controls (Cx40(fl/fl)), which were reversed by the specific KCa3.1-blocker TRAM-34. In normotensive wild-type and Cx40(fl/fl):Tie2-Cre as well as in hypertensive Cx40(-/-) animals, i.p. injections of SKA-31 (30 and 100 mg.kg(-1)) decreased arterial pressure by approximately 32 mmHg in all genotypes. The depressor response to 100 mg.kg(-1) SKA-31 was associated with a decrease in heart rate. CONCLUSIONS AND IMPLICATIONS: We conclude that endothelial hyperpolarization evoked by pharmacological activation of KCa3.1 channels induces EDH-type arteriolar dilatations that are independent of endothelial Cx40 and Cx40-containing myoendothelial gap junctions. As SKA-31 reduced blood pressure in hypertensive Cx40-deficient mice, KCa3.1 activators may be useful drugs for severe treatment-resistant hypertension.
SKA-31, a novel activator of SK(Ca) and IK(Ca) channels, increases coronary flow in male and female rat hearts.[Pubmed:23118129]
Cardiovasc Res. 2013 Feb 1;97(2):339-48.
AIMS: Endothelial SK(Ca) and IK(Ca) channels play an important role in the regulation of vascular function and systemic blood pressure. Based on our previous findings that small molecule activators of SK(Ca) and IK(Ca) channels (i.e. NS309 and SKA-31) can inhibit myogenic tone in isolated resistance arteries, we hypothesized that this class of compounds may induce effective vasodilation in an intact vascular bed, such as the coronary circulation. METHODS AND RESULTS: In a Langendorff-perfused, beating rat heart preparation, acute bolus administrations of SKA-31 (0.01-5 microg) dose-dependently increased total coronary flow (25-30%) in both male and female hearts; these responses were associated with modest, secondary increases in left ventricular (LV) systolic pressure and heart rate. SKA-31 evoked responses in coronary flow, LV pressure, and heart rate were qualitatively comparable to acute responses evoked by bradykinin (1 microg) and adenosine (10 microg). In the presence of apamin and TRAM-34, selective blockers of SK(Ca) and IK(Ca) channels, respectively, SKA-31 and bradykinin-induced responses were largely inhibited, whereas the adenosine-induced changes were blocked by approximately 40%; TRAM-34 alone produced less inhibition. Sodium nitroprusside (SNP, 0.2 mug bolus dose) evoked changes in coronary flow, LV pressure, and heart rate were similar to those induced by SKA-31, but were unaffected by apamin + TRAM-34. The NOS inhibitor L-NNA reduced bradykinin- and adenosine-evoked changes, but did not affect responses to either SKA-31 or SNP. CONCLUSION: Our study demonstrates that SKA-31 can rapidly and reversibly induce dilation of the coronary circulation in intact functioning hearts under basal flow and contractility conditions.
Genetic deficit of SK3 and IK1 channels disrupts the endothelium-derived hyperpolarizing factor vasodilator pathway and causes hypertension.[Pubmed:19380617]
Circulation. 2009 May 5;119(17):2323-32.
BACKGROUND: It has been proposed that activation of endothelial SK3 (K(Ca)2.3) and IK1 (K(Ca)3.1) K+ channels plays a role in the arteriolar dilation attributed to an endothelium-derived hyperpolarizing factor (EDHF). However, our understanding of the precise function of SK3 and IK1 in the EDHF dilator response and in blood pressure control remains incomplete. To clarify the roles of SK3 and IK1 channels in the EDHF dilator response and their contribution to blood pressure control in vivo, we generated mice deficient for both channels. METHODS AND RESULTS: Expression and function of endothelial SK3 and IK1 in IK1(-/-)/SK3(T/T) mice was characterized by patch-clamp, membrane potential measurements, pressure myography, and intravital microscopy. Blood pressure was measured in conscious mice by telemetry. Combined IK1/SK3 deficiency in IK1(-/-)/SK3(T/T) (+doxycycline) mice abolished endothelial K(Ca) currents and impaired acetylcholine-induced smooth muscle hyperpolarization and EDHF-mediated dilation in conduit arteries and in resistance arterioles in vivo. IK1 deficiency had a severe impact on acetylcholine-induced EDHF-mediated vasodilation, whereas SK3 deficiency impaired NO-mediated dilation to acetylcholine and to shear stress stimulation. As a consequence, SK3/IK1-deficient mice exhibited an elevated arterial blood pressure, which was most prominent during physical activity. Overexpression of SK3 in IK1(-/-)/SK3(T/T) mice partially restored EDHF- and nitric oxide-mediated vasodilation and lowered elevated blood pressure. The IK1-opener SKA-31 enhanced EDHF-mediated vasodilation and lowered blood pressure in SK3-deficient IK1(+/+)/SK3(T/T) (+doxycycline) mice to normotensive levels. CONCLUSIONS: Our study demonstrates that endothelial SK3 and IK1 channels have distinct stimulus-dependent functions, are major players in the EDHF pathway, and significantly contribute to arterial blood pressure regulation. Endothelial K(Ca) channels may represent novel therapeutic targets for the treatment of hypertension.
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.[Pubmed:18955585]
Mol Pharmacol. 2009 Feb;75(2):281-95.
Small-conductance (KCa2.1-2.3) and intermediate-conductance (KCa3.1) calcium-activated K(+) channels are critically involved in modulating calcium-signaling cascades and membrane potential in both excitable and nonexcitable cells. Activators of these channels constitute useful pharmacological tools and potential new drugs for the treatment of ataxia, epilepsy, and hypertension. Here, we used the neuroprotectant riluzole as a template for the design of KCa2/3 channel activators that are potent enough for in vivo studies. Of a library of 41 benzothiazoles, we identified 2 compounds, anthra[2,1-d]thiazol-2-ylamine (SKA-20) and naphtho[1,2-d]thiazol-2-ylamine (SKA-31), which are 10 to 20 times more potent than riluzole and activate KCa2.1 with EC(50) values of 430 nM and 2.9 microM, KCa2.2 with an EC(50) value of 1.9 microM, KCa2.3 with EC(50) values of 1.2 and 2.9 microM, and KCa3.1 with EC(50) values of 115 and 260 nM. Likewise, SKA-20 and SKA-31 activated native KCa2.3 and KCa3.1 channels in murine endothelial cells, and the more "drug-like" SKA-31 (half-life of 12 h) potentiated endothelium-derived hyperpolarizing factor-mediated dilations of carotid arteries from KCa3.1(+/+) mice but not from KCa3.1(-/-) mice. Administration of 10 and 30 mg/kg SKA-31 lowered mean arterial blood pressure by 4 and 6 mm Hg in normotensive mice and by 12 mm Hg in angiotensin-II-induced hypertension. These effects were absent in KCa3.1-deficient mice. In conclusion, with SKA-31, we have designed a new pharmacological tool to define the functional role of the KCa2/3 channel activation in vivo. The blood pressure-lowering effect of SKA-31 suggests KCa3.1 channel activation as a new therapeutic principle for the treatment of hypertension.