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Purity: ≥98%
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.
| Targets |
Applying 10, 30, 100, and 300 μM of sematilide inhibits delayed rectifier K+ current (IC50=25 μM) in a concentration-dependent manner [1].
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| 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].
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| 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 did not provide data on systemic toxicity, toxicokinetics, or protein binding of cermatrib. At the cellular level, cermatrib (100 µM) showed higher selectivity for I_Kr than for other major cardiac currents (I_t, I_K1, I_Na, I_Ca), suggesting that it may have good safety in terms of electrophysiological side effects. [1]
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| References | |
| Additional Infomation |
See also: Sematilide (note moved to).
Sematilide is a novel class III antiarrhythmic drug. Its main mechanism of action is the selective blocking of rapidly activated delayed rectifier potassium currents (I_Kr), thereby prolonging the action potential duration and effective refractory period in myocardial tissue. [1] Sematilide's high selectivity for I_Kr relative to 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 antiarrhythmic drug and may explain its clinical efficacy in prolonging the atrial and ventricular refractory periods. [1] |
| Molecular Formula |
C14H24CLN3O3S
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| Molecular Weight |
349.87
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| Exact Mass |
349.123
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| Elemental Analysis |
C, 48.06; H, 6.91; Cl, 10.13; N, 12.01; O, 13.72; S, 9.16
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| CAS # |
101526-62-9
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| Related CAS # |
Sematilide;101526-83-4
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| PubChem CID |
58504
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| Appearance |
White to yellow solid powder
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| Boiling Point |
511.9ºC at 760 mmHg
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| Flash Point |
263.4ºC
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| Vapour Pressure |
7.59E-11mmHg at 25°C
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| LogP |
3.476
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
22
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| Complexity |
408
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.CCN(CCNC(C1C=CC(NS(=O)(C)=O)=CC=1)=O)CC
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| InChi Key |
OKXAJGDKHKNFAX-UHFFFAOYSA-N
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| 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
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| Chemical Name |
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| 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. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| 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. View More
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. |
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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