| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| Targets |
IKs/slow delayed rectifier K+ current
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| ln Vitro |
The cystic fibrosis transmembrane conductance regulator (CFTR) and the sulphonylurea receptor subunit (SUR) of the KATP channel are both members of the ATP-binding cassette (ABC) protein superfamily. Many compounds that open or block the KATP channel by binding to SUR also inhibit the CFTR Cl- current (ICFTR); an example in point is the chromanol-type KATP channel opener, cromakalim. The structurally related chromanol 293B (trans-6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethyl-chromane), a blocker of the slow component of the delayed rectifier K+ current (IKs) in the heart, is also a weak inhibitor of KATP. This suggests that 293B may affect also ICFTR- We have addressed this question with human CFTR expressed in Xenopus oocytes. In two-electrode voltage-clamp experiments, 293B inhibited ICFTR with an IC50-value of 19 microM and Hill coefficient of 1.0; the inhibition was weakened by increasing concentrations of isobutyl-methylxanthine (IBMX). Patch-clamp recordings gave an IC50-value of 30 microM but showed a unusual variability in the sensitivity to 293B. The data show that 293B inhibits ICFTR and suggest that the mechanism of inhibition may depend on the phosphorylation state of the CFTR protein. The concentrations required for inhibition of ICFTR are three- to fivefold higher than those reported for inhibition of KvLQT1 + minK expressed in Xenopus oocytes. Since CFTR is expressed also in cardiac myocytes, the effects of 293B in these cells must be analysed with caution[1].
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| Enzyme Assay |
Excised macropatches. [1]
The patch-clamp technique (Hamill et al. 1981) was used and inside-out macropatches were excised as described by Hilgemann (1995). After shrinking the oocytes in a hypertonic solution containing 200 mM K+-aspartate at pH 7.0, the vitelline layer of the oocytes was removed with sharpened watchmaker’s forceps. Oocytes were then placed in a bath solution containing (in mM): NaCl 96, KCl 2, MgCl2 1, EGTA 2, HEPES 5; titrated to pH 7.4 with NaOH. Patch pipettes were drawn as described above and heat-polished. After filling with (in mM) NaCl 96, KCl 2, CaCl2 1.8, MgCl2 1, HEPES 5, pH 7.4, pipettes had a resistance of 250–400 kΩ. Patches were excised and clamped at –30 mV. Every 30 s, voltage was stepped from –90 mV to +50 mV in 10-mV intervals lasting 1 s. ICFTR was activated by addition of protein kinase A catalytic subunit (cPKA, 17 nM~30 U/ml) and Na2ATP (0.2 mM) to the bath solution[1]. |
| Cell Assay |
Whole oocyte voltage-clamp. [1]
Two-electrode voltage-clamp recordings (Hodgkin et al. 1952) were performed in a medium containing (in mM): NaCl 96, KCl 2, CaCl2 1.8, MgCl2 1, HEPES 5; pH 7.0 with NaOH. Microelectrodes were drawn from filament borosilicate glass capillaries (GC 150TF) using a horizontal microelectrode puller. After filling with 3 M KCl, pipettes had a resistance of 200–500 kΩ. Oocytes were clamped at –25 mV for 30 s and voltage-stepped from –90 mV to +10 mV in 10-mV steps lasting 1 s. The chloride current flowing through CFTR, ICFTR, was induced by addition of forskolin (3 µM) and isobutylmethylxanthine (IBMX, 0.1–1 mM) to the bath. 293B was added to the bath after the current reached a steady state level (after 15–25 min)[1]. |
| References | |
| Additional Infomation |
Chromanol 293B is a 1-benzopyran.
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| Molecular Formula |
C15H20N2O4S
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|---|---|
| Molecular Weight |
324.40
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| Exact Mass |
324.114
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| Elemental Analysis |
C, 55.54; H, 6.21; N, 8.64; O, 19.73; S, 9.88
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| CAS # |
163163-23-3
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| Related CAS # |
(-)-Chromanol 293B;163163-24-4
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| PubChem CID |
121846
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| Appearance |
White to off-white solid powder
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| Density |
1.33g/cm3
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| Boiling Point |
474.1ºC at 760mmHg
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| Vapour Pressure |
8.52E-10mmHg at 25°C
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| Index of Refraction |
1.592
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| LogP |
2.493
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
22
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| Complexity |
560
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CCS(=O)(=O)N(C)[C@@H]1[C@H](C(OC2=C1C=C(C=C2)C#N)(C)C)O
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| InChi Key |
HVSJHHXUORMCGK-UONOGXRCSA-N
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| InChi Code |
InChI=1S/C15H20N2O4S/c1-5-22(19,20)17(4)13-11-8-10(9-16)6-7-12(11)21-15(2,3)14(13)18/h6-8,13-14,18H,5H2,1-4H3/t13-,14+/m0/s1
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| Chemical Name |
N-[(3R,4S)-6-cyano-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl]-N-methylethanesulfonamide
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| Synonyms |
Chromanol 293B; 163163-23-3; (-)-[3R,4S]-Chromanol 293B; 293B Cpd; (-)-Chromanol 293B; 163163-24-4; (3R,4S)-293B; LS-185874;
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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 |
| 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) |
DMF: ≥ 30 mg/mL (92.48 mM)
DMSO: ≥ 30 mg/mL (92.48 mM) Ethanol: ≥ 2 mg/mL (6.17 mM) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0826 mL | 15.4131 mL | 30.8261 mL | |
| 5 mM | 0.6165 mL | 3.0826 mL | 6.1652 mL | |
| 10 mM | 0.3083 mL | 1.5413 mL | 3.0826 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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