| Bioactivity | NS309 is a potent and selective activator of the Ca2+-activated SK/IK potassium channels, but displays no activity at BK channels[1][2][3][4]. | ||||||||||||
| Target | EC50: 0.62 µM (SK2), 0.3 μM (SK3), ∼20 nM (KCa3.1/SK4), ∼600 nM (KCa2/SK channels), 10 nM (hIK) | ||||||||||||
| Invitro | NS309 (40 nM) activates both hSK3 and hIK channels, with the largest effect on hIK channels (8.5-fold increase in current compares to 1.9-fold increase in current for hSK3 channels)[2].NS309 (10 μM) significantly increases the whole cell SK currents and hyperpolarized detrusor smooth muscle (DSM) cells resting membrane potential[5].NS309 inhibits the spontaneous phasic contraction amplitude, force, frequency, duration and tone of isolated DSM strips in a concentration-dependent manner[5]. | ||||||||||||
| In Vivo | NS309 (2 mg/kg; i.p.) protects against SCI/R in rabbits[6]. Animal Model: | ||||||||||||
| Name | NS309 | ||||||||||||
| CAS | 18711-16-5 | ||||||||||||
| Formula | C8H4Cl2N2O2 | ||||||||||||
| Molar Mass | 231.04 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [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. |