Synonym
NS309; NS-309; NS 309.
IUPAC/Chemical Name
(Z)-6,7-dichloro-3-(hydroxyimino)indolin-2-one
InChi Key
CVOUSAVHMDXCKG-UHFFFAOYSA-N
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)
SMILES Code
O=C1/C(C2=CC=C(Cl)C(Cl)=C2N1)=N\O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
NS309 is a potent and selective activator of the Ca2+-activated SK/IK potassium channels.
In vitro activity:
This study has identified and characterized the compound NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) as a potent activator of human Ca2+ -activated K+ channels of SK and IK types, whereas it is devoid of effect on BK type channels. IK- and SK-channels have previously been reported to be activated by the benzimidazolinone, 1-EBIO and more potently by its dichloronated-analogue, DC-EBIO. NS309 is at least 1000 times more potent than 1-EBIO and at least 30 times more potent than DC-EBIO when the compounds are compared on the same cell.
Reference: Biochim Biophys Acta. 2004 Oct 11;1665(1-2):1-5. https://pubmed.ncbi.nlm.nih.gov/15471565/
In vivo activity:
The aim of this study was to investigate the role of SK/KCa channels in experimental SCI/R in rabbits. Treatment with 2 mg/kg NS309, a pharmacological activator for SK/KCa channel, attenuated SCI/R-induced neuronal loss, spinal cord edema and neurological dysfunction. These effects were still observed when the administration was delayed by 6 h after SCI/R initiation. NS309 decreased the levels of oxidative products and promoted activities of antioxidant enzymes in both serum and spinal cord tissues. The results of ELISA assay showed that NS309 markedly decreased levels of pro-inflammatory cytokines while increased anti-inflammatory cytokines levels after SCI/R. In addition, treatment with NS309 was shown to preserve mitochondrial respiratory complexes activities and enhance mitochondrial biogenesis.
Reference: Front Pharmacol. 2019 Apr 2;10:325. https://pubmed.ncbi.nlm.nih.gov/31001121/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
74.4 |
321.89 |
| Ethanol |
3.0 |
12.99 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
231.03
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Morimura K, Yamamura H, Ohya S, Imaizumi Y. Voltage-dependent Ca2+-channel block by openers of intermediate and small conductance Ca2+-activated K+ channels in urinary bladder smooth muscle cells. J Pharmacol Sci. 2006 Mar;100(3):237-41. doi: 10.1254/jphs.sc0060011. Epub 2006 Mar 4. PMID: 16518073.
2. Strøbaek D, Teuber L, Jørgensen TD, Ahring PK, Kjaer K, Hansen RS, Olesen SP, Christophersen P, Skaaning-Jensen B. 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. doi: 10.1016/j.bbamem.2004.07.006. PMID: 15471565.
3. Zhu J, Yang LK, Chen WL, Lin W, Wang YH, Chen T. 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 Apr 2;10:325. doi: 10.3389/fphar.2019.00325. PMID: 31001121; PMCID: PMC6454010.
4. Brøndum E, Kold-Petersen H, Simonsen U, Aalkjaer C. NS309 restores EDHF-type relaxation in mesenteric small arteries from type 2 diabetic ZDF rats. Br J Pharmacol. 2010 Jan;159(1):154-65. doi: 10.1111/j.1476-5381.2009.00525.x. Epub 2009 Dec 10. PMID: 20015296; PMCID: PMC2823361.
In vitro protocol:
1. Morimura K, Yamamura H, Ohya S, Imaizumi Y. Voltage-dependent Ca2+-channel block by openers of intermediate and small conductance Ca2+-activated K+ channels in urinary bladder smooth muscle cells. J Pharmacol Sci. 2006 Mar;100(3):237-41. doi: 10.1254/jphs.sc0060011. Epub 2006 Mar 4. PMID: 16518073.
2. Strøbaek D, Teuber L, Jørgensen TD, Ahring PK, Kjaer K, Hansen RS, Olesen SP, Christophersen P, Skaaning-Jensen B. 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. doi: 10.1016/j.bbamem.2004.07.006. PMID: 15471565.
In vivo protocol:
1. Zhu J, Yang LK, Chen WL, Lin W, Wang YH, Chen T. 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 Apr 2;10:325. doi: 10.3389/fphar.2019.00325. PMID: 31001121; PMCID: PMC6454010.
2. Brøndum E, Kold-Petersen H, Simonsen U, Aalkjaer C. NS309 restores EDHF-type relaxation in mesenteric small arteries from type 2 diabetic ZDF rats. Br J Pharmacol. 2010 Jan;159(1):154-65. doi: 10.1111/j.1476-5381.2009.00525.x. Epub 2009 Dec 10. PMID: 20015296; PMCID: PMC2823361.
1: Tajbakhsh N, Sokoya EM. Compromised endothelium-dependent hyperpolarization-mediated dilations can be rescued by NS309 in obese Zucker rats. Microcirculation. 2014 Nov;21(8):747-53. doi: 10.1111/micc.12157. PubMed PMID: 25047389.
2: Parajuli SP, Hristov KL, Soder RP, Kellett WF, Petkov GV. NS309 decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels. Br J Pharmacol. 2013 Apr;168(7):1611-25. doi: 10.1111/bph.12049. PubMed PMID: 23145946; PubMed Central PMCID: PMC3605870.
3: Kroigaard C, Dalsgaard T, Nielsen G, Laursen BE, Pilegaard H, Köhler R, Simonsen U. Activation of endothelial and epithelial K(Ca) 2.3 calcium-activated potassium channels by NS309 relaxes human small pulmonary arteries and bronchioles. Br J Pharmacol. 2012 Sep;167(1):37-47. doi: 10.1111/j.1476-5381.2012.01986.x. PubMed PMID: 22506557; PubMed Central PMCID: PMC3448912.
4: Seear RV, Lew VL. IKCa agonist (NS309)-elicited all-or-none dehydration response of human red blood cells is cell-age dependent. Cell Calcium. 2011 Nov;50(5):444-8. doi: 10.1016/j.ceca.2011.07.005. Epub 2011 Sep 21. PubMed PMID: 21937109.
5: Brøndum E, Kold-Petersen H, Simonsen U, Aalkjaer C. NS309 restores EDHF-type relaxation in mesenteric small arteries from type 2 diabetic ZDF rats. Br J Pharmacol. 2010 Jan;159(1):154-65. doi: 10.1111/j.1476-5381.2009.00525.x. Epub 2009 Dec 10. PubMed PMID: 20015296; PubMed Central PMCID: PMC2823361.
6: Pandita RK, Rønn LC, Jensen BS, Andersson KE. Urodynamic effects of intravesical administration of the new small/intermediate conductance calcium activated potassium channel activator NS309 in freely moving, conscious rats. J Urol. 2006 Sep;176(3):1220-4. PubMed PMID: 16890729.
7: Strøbaek D, Teuber L, Jørgensen TD, Ahring PK, Kjaer K, Hansen RS, Olesen SP, Christophersen P, Skaaning-Jensen B. 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. PubMed PMID: 15471565.
