ICA-27243 is a selective and orally bioactive KCNQ2/Q3 potassium channel opener with EC50 of 0.38 μM. ICA-27243 is less effective at activating KCNQ4 and KCNQ3/Q5. ICA-27243 has antiepileptic and anticonvulsant (antiepileptic/antiseizure) properties.

Physicochemical Properties

Molecular Formula	C12H7CLF2N2O
Molecular Weight	268.65
Exact Mass	268.021
CAS #	325457-89-4
PubChem CID	9903497
Appearance	White to off-white solid powder
LogP	3.649
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	18
Complexity	306
Defined Atom Stereocenter Count	0
InChi Key	GDGUOCFTHNGPBK-UHFFFAOYSA-N
InChi Code	InChI=1S/C12H7ClF2N2O/c13-11-4-2-8(6-16-11)17-12(18)7-1-3-9(14)10(15)5-7/h1-6H,(H,17,18)
Chemical Name	N-(6-chloropyridin-3-yl)-3,4-difluorobenzamide
Synonyms	ICA27243 ICA 27243 ICA-27243
HS Tariff Code	2934.99.9001
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)

Biological Activity

ln Vitro	Coadministration of XE-991 and Linopirdine, two M current inhibitors, can decrease the membrane potential hyperpolarization that ICA-27243 causes in human neuroblastoma cells (SH-SY5Y). In Chinese hamster ovary cells that stably express heteromultimeric KCNQ2/Q3 channels, ICA-27243 increases 86Rb+ efflux (EC50 = 0.2 μM) and whole-cell currents (EC50 = 0.4 μM). The hyperpolarization shift that occurs when KCNQ2/Q3 channels are activated is reliant on the channel activation voltage (V1/2 shift of -19 mV at 10 μM) [1].
ln Vivo	In a mouse maximum electroshock epilepsy paradigm, ICA-27243 (1-100 mg/kg; oral; male CD-1 mice) exhibits anticonvulsant action (ED50 of 8.4 mg/kg) [1].
Animal Protocol	Animal/Disease Models: Male CD-1 mice, electric shock test [1] Doses: 1-100 mg/kg Route of Administration: Oral Experimental Results:There was a dose-dependent increase in hindlimb extension latency, with an ED50 value of 8.4 mg/kg.
References	[1]. N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide (ICA-27243): a novel, selective KCNQ2/Q3 potassium channel activator. Mol Pharmacol. 2008 Mar;73(3):977-86. [2]. N-Pyridyl and Pyrimidine Benzamides as KCNQ2/Q3 Potassium Channel Openers for the Treatment of Epilepsy. ACS Med Chem Lett. 2011 Mar 31;2(6):481-4.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~930.58 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (7.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.7223 mL	18.6116 mL	37.2232 mL
	5 mM	0.7445 mL	3.7223 mL	7.4446 mL
	10 mM	0.3722 mL	1.8612 mL	3.7223 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.