Sematilide (formerly known as CK-1752) is a novel class III antiarrhythmic agent. It acts as a selective delayed rectifier K+ current (IKr) channel blocker. I The sematilide-sensitive current, which was recorded by means of a triangular voltage command, showed a strong inward rectification and had a peak at about -40 mV, suggesting that sematilide inhibits the rapidly activating delayed rectifier K+ current. The Ca2+-independent transient K+ and the inward rectifier K+ currents were not affected significantly by application of 100 microM sematilide. Moreover, voltage-dependent Na+ and Ca2+ currents were not affected significantly by 100 microM sematilide. These findings indicate that sematilide selectively blocks the rapidly activating delayed rectifier K+ current in atrial myocytes and provide evidence supporting the usefulness of the drug as a class III antiarrhythmic agent.

Physicochemical Properties

Molecular Formula	C14H24CLN3O3S
Molecular Weight	349.87
Exact Mass	349.123
Elemental Analysis	C, 48.06; H, 6.91; Cl, 10.13; N, 12.01; O, 13.72; S, 9.16
CAS #	101526-62-9
Related CAS #	Sematilide;101526-83-4
PubChem CID	58504
Appearance	White to yellow solid powder
Boiling Point	511.9ºC at 760 mmHg
Flash Point	263.4ºC
Vapour Pressure	7.59E-11mmHg at 25°C
LogP	3.476
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	8
Heavy Atom Count	22
Complexity	408
Defined Atom Stereocenter Count	0
SMILES	Cl.CCN(CCNC(C1C=CC(NS(=O)(C)=O)=CC=1)=O)CC
InChi Key	OKXAJGDKHKNFAX-UHFFFAOYSA-N
InChi Code	InChI=1S/C14H23N3O3S.ClH/c1-4-17(5-2)11-10-15-14(18)12-6-8-13(9-7-12)16-21(3,19)20;/h6-9,16H,4-5,10-11H2,1-3H3,(H,15,18);1H
Chemical Name	Benzamide, N-(2-(diethylamino)ethyl)-4-((methylsulfonyl)amino)-, monohydrochloride
Synonyms	CK-1752A HCl; CK1752A; CK 1752A; CK-1752 HCl; CK1752; CK 1752; Sematilide hydrochloride; Sematilide HCl; Sematilide hydrochloride; Sematilide;
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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

Targets	Applying 10, 30, 100, and 300 μM of sematilide inhibits delayed rectifier K+ current (IC50=25 μM) in a concentration-dependent manner [1].
ln Vitro	Applying 10, 30, 100, and 300 μM of sematilide inhibits delayed rectifier K+ current (IC50=25 μM) in a concentration-dependent manner [1]. Sematilide (10, 30, 100, 300 µM) causes a concentration-dependent inhibition of the delayed rectifier K⁺ current (I_K) tail current (I_K-tail) in enzymatically isolated rabbit left atrial myocytes, with an IC50 of approximately 25 µM. Application of 300 µM sematilide almost completely blocks I_K-tail. [1] The sematilide-sensitive current (I_sema) exhibits strong inward rectification and peaks around -40 mV, characteristic of the rapidly activating component I_Kr. The inhibition of I_K by sematilide is not voltage-dependent over the range of +1 to +41 mV. [1] Sematilide (100 µM) does not significantly affect the Ca²⁺-independent transient outward K⁺ current (I_t) in rabbit atrial myocytes. [1] Sematilide (100 µM) does not significantly affect the inward rectifier K⁺ current (I_K1) in rabbit atrial myocytes. [1] Sematilide (100 µM) does not significantly affect the voltage-dependent Na⁺ current (I_Na) in rabbit atrial myocytes. [1] Sematilide (100 µM) does not significantly affect the voltage-dependent Ca²⁺ current (I_Ca, primarily L-type) in rabbit atrial myocytes. [1]
ln Vivo	In dogs with arrhythmia models, simalide (0.3–1.0 mg/kg, intravenous injection) works well [2].
Cell Assay	Isolation of Rabbit Atrial Myocytes: Hearts from young male rabbits were perfused on a Langendorff system with normal Krebs solution, followed by Ca²⁺-free Krebs solution, and then Ca²⁺-free Krebs solution containing collagenase. After enzyme washout with KB solution, the left atrium was dissociated by gentle agitation. Cells were stored in a high Mg²⁺, Ca²⁺-free HEPES-buffered solution with gradual addition of Ca²⁺ and used within 12 hours. [1] Whole-Cell Voltage Clamp Recording: Ionic currents were recorded from single atrial myocytes using the whole-cell patch-clamp technique at 36°C. Pipettes were filled with an internal solution containing K-aspartate, KCl, MgCl₂, CaCl₂, EGTA, Na₂ATP, and HEPES (pCa 7.5). The standard external solution contained NaCl, KCl, CaCl₂, MgCl₂, glucose, and HEPES. Specific current isolations: I_K was recorded in the presence of CoCl₂ to block I_Ca; I_t was recorded in the presence of CdCl₂ to block I_Ca; I_K1 was recorded as the Ba²⁺-sensitive current in the presence of CdCl₂; I_Na was recorded at 10°C in a solution with reduced Na⁺ (replaced by tetraethylammonium) and CdCl₂; I_Ca was recorded in the presence of 4-aminopyridine to block I_t. Drugs were applied via the bathing solution. Currents were digitized and analyzed using computer software. [1]
Animal Protocol	Animal/Disease Models: Mongrel dogs of either sex (body weight 10-18 kg) [2] Doses: 0.3, 1, 3 and 10 mg/kg Route of Administration: intravenous (iv) (iv)infusion Experimental Results: 0.3 and 3.0 mg/kg demonstrated antirhythmic effects Abnormal effects.
Toxicity/Toxicokinetics	This study does not provide systemic toxicity, toxicokinetic, or protein binding data for sematilide. At the cellular level, sematilide (100 µM) showed high selectivity for I_Kr over other major cardiac currents (I_t, I_K1, I_Na, I_Ca), suggesting a potentially favorable safety profile regarding electrophysiological side effects. [1]
References	[1]. Effects of Sematilide, a novel class III antiarrhythmic agent, on membrane currents in rabbit atrial myocytes. Eur J Pharmacol. 1997 Jul 23;331(2-3):295-302. [2]. Pharmacology of Sematilide, a non-quaternary class III antiarrhythmic agent.
Additional Infomation	See also: Sematilide (annotation moved to). Sematilide is a novel class III antiarrhythmic agent. Its primary mechanism of action is selective blockade of the rapidly activating delayed rectifier K⁺ current (I_Kr), which prolongs the action potential duration and effective refractory period in cardiac tissue. [1] The high selectivity of sematilide for I_Kr over other repolarizing currents (I_t, I_K1) and depolarizing currents (I_Na, I_Ca) in atrial myocytes supports its classification as a "pure" class III agent and may underlie its clinical effects in prolonging atrial and ventricular refractory periods. [1]

Solubility Data

Solubility (In Vitro)

DMSO: >10 mM Water:N/A Ethanol:N/A

Solubility (In Vivo)

Solubility in Formulation 1: 0.5 mg/mL (1.43 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 0.5 mg/mL (1.43 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: 0.5 mg/mL (1.43 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 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	2.8582 mL	14.2910 mL	28.5820 mL
	5 mM	0.5716 mL	2.8582 mL	5.7164 mL
	10 mM	0.2858 mL	1.4291 mL	2.8582 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.