Chromanol 293BIKs blocker. Also blocks ICFTR CAS# 163163-23-3 |
- Hydroxyfasudil
Catalog No.:BCC1635
CAS No.:105628-72-6
- Y-27632 dihydrochloride
Catalog No.:BCC1273
CAS No.:129830-38-2
- Hydroxyfasudil hydrochloride
Catalog No.:BCC1636
CAS No.:155558-32-0
- H-1152
Catalog No.:BCC1615
CAS No.:451462-58-1
- H-1152 dihydrochloride
Catalog No.:BCC1616
CAS No.:871543-07-6
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 163163-23-3 | SDF | Download SDF |
PubChem ID | 56846045 | Appearance | Powder |
Formula | C15H20N2O4S | M.Wt | 324.39 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | Soluble to 20 mM in ethanol and to 100 mM in DMSO | ||
Chemical Name | N-[(3S,4S)-6-Cyano-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-N-methylethanesulfonamide | ||
SMILES | CCS(=O)(=O)N(C)C1C(C(OC2=C1C=C(C=C2)C#N)(C)C)O | ||
Standard InChIKey | HVSJHHXUORMCGK-KBPBESRZSA-N | ||
Standard InChI | 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 | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | Blocker of the slow delayed rectifier K+ current (IKs) (IC50 = 1-10 μM). Also blocks the CFTR chloride current (ICFTR) (IC50 = 19 μM). (-)-[3R,4S]-Chromanol 293B also available. |
Chromanol 293B Dilution Calculator
Chromanol 293B Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 3.0827 mL | 15.4135 mL | 30.8271 mL | 61.6542 mL | 77.0677 mL |
5 mM | 0.6165 mL | 3.0827 mL | 6.1654 mL | 12.3308 mL | 15.4135 mL |
10 mM | 0.3083 mL | 1.5414 mL | 3.0827 mL | 6.1654 mL | 7.7068 mL |
50 mM | 0.0617 mL | 0.3083 mL | 0.6165 mL | 1.2331 mL | 1.5414 mL |
100 mM | 0.0308 mL | 0.1541 mL | 0.3083 mL | 0.6165 mL | 0.7707 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
- Cannabisin F
Catalog No.:BCN4696
CAS No.:163136-19-4
- BYK 49187
Catalog No.:BCC2450
CAS No.:163120-31-8
- N-Benzylmaleimide
Catalog No.:BCC9095
CAS No.:1631-26-1
- Albatrelin G
Catalog No.:BCN7596
CAS No.:1630970-05-6
- 17-Hydroxy-18-dehydroneogrifolin
Catalog No.:BCN7633
CAS No.:1630936-42-3
- Huperzine C
Catalog No.:BCN2489
CAS No.:163089-71-2
- (1S,2S)-1-Amino-2-Indanol
Catalog No.:BCC8386
CAS No.:163061-74-3
- (1R,2R)-1-Amino-2-indanol
Catalog No.:BCC8380
CAS No.:163061-73-2
- Lup-20(29)-ene-3bate,23-diol
Catalog No.:BCN4080
CAS No.:163060-07-9
- Cimicifugoside H1
Catalog No.:BCN7950
CAS No.:163046-73-9
- 2-Cl-IB-MECA
Catalog No.:BCC6938
CAS No.:163042-96-4
- 3-O-(2-Aminoethyl)-25-hydroxyvitamin D3
Catalog No.:BCC1309
CAS No.:163018-26-6
- (-)-[3R,4S]-Chromanol 293B
Catalog No.:BCC7080
CAS No.:163163-24-4
- Cimifugin 4'-O-beta-D-glucopyranoside
Catalog No.:BCN7853
CAS No.:1632110-81-6
- Ezetimibe
Catalog No.:BCN2180
CAS No.:163222-33-1
- 680C91
Catalog No.:BCC6158
CAS No.:163239-22-3
- Clevudine
Catalog No.:BCC4770
CAS No.:163252-36-6
- Sitafloxacin Hydrate
Catalog No.:BCC4959
CAS No.:163253-35-8
- Bethoxazin
Catalog No.:BCC5471
CAS No.:163269-30-5
- FIIN-2
Catalog No.:BCC3974
CAS No.:1633044-56-0
- Stachybotrylactam
Catalog No.:BCN6967
CAS No.:163391-76-2
- 2',4'-Di-O-(E-p-coumaroyl)afzelin
Catalog No.:BCN6512
CAS No.:163434-73-9
- Fmoc-Met(O2)-OH
Catalog No.:BCC3531
CAS No.:163437-14-7
- Flufenamic acid
Catalog No.:BCC9162
CAS No.:530-78-9
Models of torsades de pointes: effects of FPL64176, DPI201106, dofetilide, and chromanol 293B in isolated rabbit and guinea pig hearts.[Pubmed:19524054]
J Pharmacol Toxicol Methods. 2009 Sep-Oct;60(2):174-84.
INTRODUCTION: For studying the torsades de pointes (TdP) liability of a compound, most high and medium throughput methods use surrogate markers such as HERG inhibition and QT prolongation. In this study, we have tested whether isolated hearts may be modified to allow TdP to be the direct readout. METHOD: Isolated spontaneously beating rabbit and guinea pig hearts were perfused according to the Langendorff method in hypokalemic (2.1 mM) solution. The in vitro lead II ECG equivalent and the incidence of TdP were monitored for 1 h. In addition, heart rate, QTc, Tp-Te, short-term variability (STV), time to arrhythmia, and time to TdP were also analyzed. RESULTS: FPL64176, a calcium channel activator; and DPI201106, a sodium channel inactivation inhibitor, produced TdP in isolated rabbit and guinea pig hearts in a concentration dependent manner; guinea pig hearts were 3- to 5-fold more sensitive than rabbit hearts. Both compounds also increased QTc and STV. In contrast, dofetilide, an IKr inhibitor, produced no (or a low incidence of) TdP in both species, in spite of prolongation of QTc intervals. Chromanol 293B, an IKs inhibitor, did not produce TdP in rabbit hearts but elicited TdP concentration dependently in guinea pig hearts even though the compound had no effect on QTc intervals. CONCLUSION: IKs inhibition appears to be more likely to produce TdP in isolated guinea pig hearts than IKr inhibition. Chromanol 293B did not produce TdP in rabbit hearts presumably due to a low level of IKs channels in the heart. TdP produced in this study was consistent with the notion that its production was a consequence of reduced repolarization reserve, thereby causing rhythmic abnormalities. This isolated, perfused, and spontaneously beating rabbit and guinea pig heart preparation in hypokalemic medium may be useful as a preclinical test model for studying proarrhythmic liability of compounds in new drug development.
Chromanol 293B binding in KCNQ1 (Kv7.1) channels involves electrostatic interactions with a potassium ion in the selectivity filter.[Pubmed:17347319]
Mol Pharmacol. 2007 Jun;71(6):1503-11.
The Chromanol 293B (293B, trans-6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethyl-chroman) is a lead compound of potential class III antiarrhythmics that inhibit cardiac I(Ks) potassium channels. These channels are formed by the coassembly of KCNQ1 (Kv7.1, KvLQT1) and KCNE1 subunits. Although homomeric KCNQ1 channels are the principal molecular targets, entry of KCNE1 to the channel complex enhances the chromanol block. Because closely related neuronal KCNQ2 potassium channels are insensitive to the drug, we used KCNQ1/KCNQ2 chimeras to identify the binding site of the inhibitor. We localized the putative drug receptor to the H5 selectivity filter and the S6 transmembrane segment. Single residues affecting 293B inhibition were subsequently identified through systematic exchange of amino acids that were either different in KCNQ1 and KCNQ2 or predicted by a docking model of 293B in the open and closed conformation of KCNQ1. Mutant channel proteins T312S, I337V, and F340Y displayed dramatically lowered sensitivity to chromanol block. The predicted drug binding receptor lies in the inner pore vestibule containing the lower part of the selectivity filter, and the S6 transmembrane domain also reported to be important for binding of benzodiazepines. We propose that the block of the ion permeation pathway involves hydrophobic interactions with the S6 transmembrane residues Ile337 and Phe340, and stabilization of Chromanol 293B binding through electrostatic interactions of its oxygen atoms with the most internal potassium ion within the selectivity filter.
Chromanol 293B, an inhibitor of KCNQ1 channels, enhances glucose-stimulated insulin secretion and increases glucagon-like peptide-1 level in mice.[Pubmed:25437377]
Islets. 2014;6(4):e962386.
Glucose-stimulated insulin secretion (GSIS) is a highly regulated process involving complex interaction of multiple factors. Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) is a susceptibility gene for type 2 diabetes (T2D) and the risk alleles of the KCNQ1 gene appear to be associated with impaired insulin secretion. The role of KCNQ1 channel in insulin secretion has been explored by previous work in clonal pancreatic beta-cells but has yet to be investigated in the context of primary islets as well as intact animals. Genetic studies suggest that altered incretin glucagon-like peptide-1 (GLP-1) secretion might be a potential link between KCNQ1 variants and impaired insulin secretion, but this hypothesis has not been verified so far. In the current study, we examined KCNQ1 expression in pancreas and intestine from normal mice and then investigated the effects of Chromanol 293B, a KCNQ1 channel inhibitor, on insulin secretion in vitro and in vivo. By double-immunofluorescence staining, KCNQ1 was detected in insulin-positive beta-cells and GLP-1-positive L-cells. Administration of Chromanol 293B enhanced GSIS in cultured islets and intact animals. Along with the potentiated insulin secretion during oral glucose tolerance tests (OGTT), plasma GLP-1 level after gastric glucose load was increased in 293B treated mice. These data not only provided new evidence for the participation of KCNQ1 in GSIS at the level of pancreatic islet and intact animal but also indicated the potential linking role of GLP-1 between KCNQ1 and insulin secretion.
Renal defects in KCNE1 knockout mice are mimicked by chromanol 293B in vivo: identification of a KCNE1-regulated K+ conductance in the proximal tubule.[Pubmed:21576273]
J Physiol. 2011 Jul 15;589(Pt 14):3595-609.
KCNE1 is a protein of low molecular mass that is known to regulate the Chromanol 293B and clofilium-sensitive K+ channel, KCNQ1, in a number of tissues. Previous work on the kidney of KCNE1 and KCNQ1 knockout mice has revealed that these animals have different renal phenotypes, suggesting that KCNE1 may not regulate KCNQ1 in the renal system. In the current study, in vivo clearance approaches and whole cell voltage-clamp recordings from isolated renal proximal tubules were used to examine the physiological role of KCNE1. Data from wild-type mice were compared to those from KCNE1 knockout mice. In clearance studies the KCNE1 knockout mice had an increased fractional excretion of Na+, Cl-, HCO3(-) and water. This profile was mimicked in wild-type mice by infusion of Chromanol 293B, while chromanol was without effect in KCNE1 knockout animals. Clofilium also increased the fractional excretion of Na+, Cl- and water, but this was observed in both wild-type and knockout mice, suggesting that KCNE1 was regulating a chromanol-sensitive but clofilium-insensitive pathway. In whole cell voltage clamp recordings from proximal tubules, a chromanol-sensitive, K+-selective conductance was identified that was absent in tubules from knockout animals. The properties of this conductance were not consistent with its being mediated by KCNQ1, suggesting that KCNE1 regulates another K+ channel in the renal proximal tubule. Taken together these data suggest that KCNE1 regulates a K+-selective conductance in the renal proximal tubule that plays a relatively minor role in driving the transport of Na+, Cl- and HCO3(-).
Chromanol 293B, a blocker of the slow delayed rectifier K+ current (IKs), inhibits the CFTR Cl- current.[Pubmed:11414653]
Naunyn Schmiedebergs Arch Pharmacol. 2001 Jun;363(6):590-6.
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.
Chromanol 293B inhibits slowly activating delayed rectifier and transient outward currents in canine left ventricular myocytes.[Pubmed:11332571]
J Cardiovasc Electrophysiol. 2001 Apr;12(4):472-8.
INTRODUCTION: Drugs that selectively inhibit the slowly activating component of the delayed rectifier potassium current (I(Ks)) are being considered as possible antiarrhythmic agents, because they produce more prolongation of action potential duration at fast rates with less transmural dispersion of repolarization compared with blockers of the rapidly activating component (I(Kr)). Although the chromanol derivative Chromanol 293B has been shown to be relatively selective in blocking I(Ks) in some species, its selectivity is far from established. METHODS AND RESULTS: The present study uses whole-cell, patch-clamp technique to examine the selectivity of this compound for inhibition of I(Ks) in comparison with other repolarizing ionic currents, such as I(Kr), inward rectifier potassium current (I(Kl)), transient outward current (I(to)), and L-type calcium current (I(Ca-L)) in canine left ventricular mid-myocardial and endocardial cells. Chromanol 293B blocked I(Ks) with an IC50 of 1.8 microM and I(to) with an IC50 of 38 microM. Concentrations as high as 30 microM did not affect I(Kl), I(Kr), or I(Ca-L). Higher concentrations of Chromanol 293B (100 microM) caused a slight, but statistically insignificant, inhibition of I(Kr). CONCLUSION: Our results indicate that Chromanol 293B is a relatively selective blocker of I(Ks) in canine left ventricular myocytes.
Time-dependent block of the slowly activating delayed rectifier K(+) current by chromanol 293B in guinea-pig ventricular cells.[Pubmed:10696102]
Br J Pharmacol. 2000 Mar;129(5):1007-13.
The slowly activating delayed rectifier K(+) current (I(Ks)) was recorded in single myocytes dissociated from guinea-pig ventricles and the mechanism underlying the block of I(Ks) by a chromanol derivative, 293B, was investigated. In the presence of 1 - 100 microM 293B, activation phase of I(Ks) was followed by a slower decay during 10 s depolarizing pulses. Both the rate and extent of the decay were increased in a concentration-dependent manner. The relationship between the concentration of 293B and the block showed a Hill's coefficient of approximately 1. The half-inhibitory concentration was approximately 3.0 microM and did not differ significantly at various membrane potentials from +20 to +80 mV. A mathematical model for the 293B block was constructed on the basis of multiple closed and open states for the I(Ks) channels, and the blocking rate was calculated by fitting the model to the original current traces. The blocking rate constant showed a linear function with the 293B concentration, indicating 1 : 1 binding stoichiometry. At +80 mV the blocking rate was 4x10(4) M(-1) s(-1) and the unblocking rate was 0.2 s(-1). The results indicate that 293B is an open channel blocker with relatively smaller blocking rate than those reported so far for time-dependent blockade of various ionic channels.