| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IKs/slow delayed rectifier K+ current
Chromanol 293B selectively targets the KCNQ1 (Kv7.1) potassium channel, particularly when co-assembled with the KCNE1 (minK) beta-subunit to form the cardiac IKs channel. It blocks IKs with an IC50 of 6.89 uM in Xenopus oocytes expressing rat KCNQ1/KCNE1. Chromanol 293B also blocks CFTR chloride current. The compound modulates pancreatic function: it promotes insulin secretion and improves glucose metabolism by acting directly on pancreatic beta-cells and indirectly elevating GLP-1 levels. |
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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].
In vitro, chromanol 293B blocks the slow delayed rectifier K+ current (IKs) via KCNQ1 (Kv7.1) channels. It also blocks CFTR chloride current. Chromanol 293B promotes insulin secretion in pancreatic beta-cells and improves glucose-stimulated insulin secretion (GSIS). It increases glucose-stimulated insulin secretion by modulating potassium voltage-gated KCNQ1 channels. Chromanol 293B also indirectly elevates GLP-1 levels. The compound is used to study cardiac electrophysiology, insulin secretion, and epithelial ion transport. |
| ln Vivo |
In vivo, chromanol 293B has been shown to enhance glucose-stimulated insulin secretion (GSIS) in the pancreas and increase glucagon-like peptide-1 (GLP-1) levels in mice, thereby improving glucose metabolism. It is used to study cardiac arrhythmias and the role of IKs channels in ventricular repolarization. Chromanol 293B can be administered to rodents via intraperitoneal injection for metabolic studies.
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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]. To assess IKs channel block, Xenopus oocytes are injected with cRNA encoding rat KCNQ1 and KCNE1 subunits. After 2-5 days of expression, two-electrode voltage-clamp recordings are performed. IKs currents are elicited by depolarizing voltage steps from -80 mV to +60 mV. Chromanol 293B is applied at increasing concentrations (0.1-100 uM) in the bath solution, and the percentage of current inhibition is calculated. The IC50 is determined by fitting dose-response curves. For CFTR inhibition, similar assays are performed in oocytes or cells expressing CFTR. For selectivity, assays on other potassium channels are performed. |
| 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]. For cell-based assays, pancreatic beta-cell lines (e.g., INS-1, MIN6) or isolated mouse pancreatic islets are used. Cells are treated with chromanol 293B at concentrations ranging from 1-30 uM in Krebs-Ringer buffer containing glucose (e.g., 2.8-16.7 mM). Insulin secretion is measured by ELISA or RIA after 1-2 hours of incubation. For GLP-1 studies, intestinal L-cells (e.g., GLUTag cells) are treated similarly. Cell viability is assessed by MTT assay. For cardiac studies, primary cardiomyocytes or iPSC-derived cardiomyocytes are used, and action potential duration (APD) is measured by patch-clamp or multi-electrode array. |
| Animal Protocol |
For in vivo metabolic studies, chromanol 293B is formulated in a suitable vehicle (e.g., DMSO followed by dilution in PBS or saline) and administered via intraperitoneal injection to mice at doses ranging from 10-50 mg/kg. Blood glucose levels are measured at various time points (0, 15, 30, 60, 120 minutes) using a glucometer. Insulin levels are measured by ELISA. For GLP-1 studies, plasma GLP-1 levels are measured after glucose challenge. For cardiac studies, chromanol 293B (5-20 mg/kg) may be administered intravenously or intraperitoneally, and ECGs are recorded to measure QT interval.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for chromanol 293B are limited. The compound has a molecular weight of 324.4 and moderate lipophilicity. For in vivo studies, it is typically dissolved in DMSO or ethanol and then diluted in PBS or saline. For species-specific PK parameters (Cmax, Tmax, t1/2, bioavailability), researchers should consult the primary literature. Solubility: Chromanol 293B is soluble in DMSO (18 mg/mL). For in vitro use, stock solutions are prepared in DMSO and diluted to final concentration in assay buffer (final DMSO <0.1%).
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| Toxicity/Toxicokinetics |
Published toxicology data for chromanol 293B are limited. In cell-based assays at concentrations used for IKs block (1-30 uM), no significant cytotoxicity has been reported. In animal studies at effective doses for insulin secretion (10-50 mg/kg), no severe adverse events have been reported. As a potassium channel blocker, chromanol 293B has the potential to prolong the QT interval in the heart, which could be pro-arrhythmic at high doses. The compound is for research use only and should be handled with standard laboratory safety precautions.
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| References | |
| Additional Infomation |
Chromanol 293B is a 1-benzopyran.
Chromanol 293B is a research tool compound and is not approved for clinical use. It is widely used as a standard IKs (KCNQ1/KCNE1) channel blocker in cardiac electrophysiology and has served as a pharmacological tool for dissecting the role of IKs in ventricular repolarization and arrhythmia mechanisms. Chromanol 293B has also been used in pancreatic beta-cell research to study the role of KCNQ1 channels in insulin secretion. The compound should be stored at -20degC as a powder, protected from light and moisture. |
| 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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