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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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1g |
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NS309 is a nonselective activator of small- and intermediate-conductance Ca2+-activated K+ (SK/KCa2 and IK/KCa3.1) channels (EC50s range from 0.12-1.2 µM for SK channels and 10-90 nM for IK channels). NS309 decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels. NS309 restores EDHF-type relaxation in mesenteric small arteries from type 2 diabetic ZDF rats.
ln Vitro |
hSK3 and hIK channels are activated by NS309 (40 nM), with hIK channels experiencing the largest effects (an 8.5-fold increase in current and a 1.9-fold rise in hSK3 channel current) [2]. The whole-cell SK currents are greatly increased and the resting membrane potential of the detrusor smooth muscle (DSM) cell is hyperpolarized by NS309 (10 μM) [5]. In a concentration-dependent manner, NS309 suppresses the amplitude, force, frequency, duration, pitch, and spontaneous phasic contraction of isolated DSM strips [5].
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ln Vivo |
In rabbits, SCI/R is prevented by NS309 (2 mg/kg; intraperitoneal injection) [6].
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Animal Protocol |
Animal/Disease Models: Adult New Zealand White Rabbit (2.5-3.0 kg) [6]
Doses: 2 mg/kg Route of Administration: intraperitoneal (ip) injection Experimental Results: Neurological outcomes in SCI/R-challenged rabbits were Dramatically improved. |
References |
[1]. Specific enhancement of SK channel activity selectively potentiates the afterhyperpolarizing current I(AHP) and modulates the firing properties of hippocampal pyramidal neurons.
[2]. C Hougaard, et al. Selective positive modulation of the SK3 and SK2 subtypes of small conductance Ca2+-activated K+ channels. Br J Pharmacol. 2007 Jul; 151(5): 655–665. [3]. Nichole Coleman, et al. New Positive Ca2+-Activated K+ Channel Gating Modulators with Selectivity for KCa3.1. Mol Pharmacol. 2014 Sep; 86(3): 342–357. [4]. Dorte Strøbaek, et al. Activation of human IK and SK Ca2+-activated K+ channels by NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime). Biochim Biophys Acta. 2004 Oct 11;1665(1-2):1-5. [5]. Shankar P Parajuli, et al. NS309 decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels. Br J Pharmacol. 2013 Apr; 168(7): 1611–1625. [6]. Jie Zhu, et al. Activation of SK/KCa Channel Attenuates Spinal Cord Ischemia-Reperfusion Injury via Anti-oxidative Activity and Inhibition of Mitochondrial Dysfunction in Rabbits. Front Pharmacol. 2019; 10: 325. |
Molecular Formula |
C8H4CL2N2O2
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Molecular Weight |
231.032
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Exact Mass |
229.965
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CAS # |
18711-16-5
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Related CAS # |
18711-16-5
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
O=C1/C(C2=CC=C(Cl)C(Cl)=C2N1)=N\O
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InChi Key |
CVOUSAVHMDXCKG-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C8H4Cl2N2O2/c9-4-2-1-3-6(5(4)10)11-8(13)7(3)12-14/h1-2,14H,(H,11,12,13)
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Chemical Name |
(Z)-6,7-dichloro-3-(hydroxyimino)indolin-2-one
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Synonyms |
NS309 NS-309 NS 309.
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO : ~100 mg/mL (~432.83 mM)
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Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 4.3284 mL | 21.6422 mL | 43.2844 mL | |
5 mM | 0.8657 mL | 4.3284 mL | 8.6569 mL | |
10 mM | 0.4328 mL | 2.1642 mL | 4.3284 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.