NS-1643

[Description]:

NS1643 is a potent human ether-a-go-go related gene (hERG) KV11.1 channel activator (EC50 = 10.5 μM).IC50 value:Target: HERG activatorin vitro: NS1643 enhanced the magnitude of wild-type hERG current in a concentration- and voltage-dependent manner with an EC(50) of 10.4 microM at -10 mV. The fully activated current-voltage relationship revealed that the drug increased outward but not inward currents, consistent with altered inactivation gating. NS1643 shifted the voltage dependence of inactivation by +21 mV at 10 microM and +35 mV at 30 microM, but it did not alter the voltage dependence of activation of hERG channels [1]. In Xenopus laevis oocytes, NS1643 increased both steady-state and tail current at all voltages tested. The EC(50) value for HERG channel activation was 10.5 microM [2]. NS1643 also activates the ERG2 channel; however, the molecular mechanism of the activation differs between the ERG1 and ERG2 channels. For ERG2, NS1643 causes a left-ward shift of the activation curve, a faster time-constant of activation and a slower time-constant of inactivation as well as an increased relative importance for the fast component of deactivation to the total deactivation. In contrast, for ERG1, NS1643 causes a right-ward shift in the voltage-dependent release from inactivation but does not affect time-constants of deactivation [3].

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

Research Areas >> Others

[References]

[1]. Casis O, et al. Mechanism of action of a novel human ether-a-go-go-related gene channel activator. Mol Pharmacol. 2006 Feb;69(2):658-65.

[2]. Hansen RS, et al. Activation of human ether-a-go-go-related gene potassium channels by the diphenylurea 1,3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643). Mol Pharmacol. 2006 Jan;69(1):266-77.

[3]. Elmedyb P, et al. Activation of ERG2 potassium channels by the diphenylurea NS1643. Neuropharmacology. 2007 Aug;53(2):283-94.

[Related Small Molecules]

[ Density]:
1.627g/cm3

[ Boiling Point ]:
342.311ºC at 760 mmHg

[ Molecular Formula ]:
C₁₅H₁₀F₆N₂O₃

[ Molecular Weight ]:
380.24200

[ Flash Point ]:
160.824ºC

[ Exact Mass ]:
380.06000

[ PSA ]:
81.59000

[ LogP ]:
4.92540

[ Appearance of Characters ]:
white solid

[ Index of Refraction ]:
1.589

[ Storage condition ]:
-20℃

Click to get detail MSDS

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301-H319

[ Precautionary Statements ]:
P301 + P310-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Faceshields;Gloves

[ RIDADR ]:
UN 2811 6.1 / PGIII

The human ether-a-go-go-related gene activator NS1643 enhances epilepsy-associated KCNQ channels.

J. Pharmacol. Exp. Ther. , (2014)

Human ether-a-go-go-related gene (hERG) and KCNQ channels are two classes of voltage-gated potassium channels. Specific mutations have been identified that are causal for type II long QT (LQT2) syndro...

Hydroxymethylation of microRNA-365-3p Regulates Nociceptive Behaviors via Kcnh2.

J. Neurosci. 36 , 2769-81, (2016)

DNA 5-hydroxylmethylcytosine (5hmC) catalyzed by ten-eleven translocation methylcytosine dioxygenase (TET) occurs abundantly in neurons of mammals. However, the in vivo causal link between TET dysregu...

Potassium channel activation inhibits proliferation of breast cancer cells by activating a senescence program.

Cell Death Dis. 4 , e652, (2013)

Traditionally the hERG1 potassium channel has been known to have a fundamental role in membrane excitability of several mammalian cells including cardiac myocytes. hERG1 has recently been found to be ...

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