| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Cromakalim targets ATP-sensitive potassium (KATP) channels, specifically the SUR2-Kir6.x subtype. By binding to the sulfonylurea receptor (SUR) subunit, it promotes channel opening, leading to potassium efflux and membrane hyperpolarization. This hyperpolarization closes voltage-dependent calcium channels, reducing calcium influx and causing smooth muscle relaxation. The compound's action is dependent on the presence of intracellular ATP and is modulated by nucleotide diphosphates.
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| ln Vitro |
In vitro, Cromakalim acts as a potent activator of KATP channels, exhibiting significant effects on various physiological systems. It induces relaxation of pre-contracted vascular smooth muscle preparations, with an EC25 value of 8.9 µM for its anti-ischemic effects. In isolated rat lymphatic vessels, it has been used to study responses to acute increases in downstream pressure. Additionally, it modulates neurotransmitter release from adrenergic, purinergic, and cholinergic nerves in rat tissues.
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| ln Vivo |
In vivo, Cromakalim displays antihypertensive activity by relaxing vascular smooth muscle to lower blood pressure. It also exhibits cardioprotective and anti-ischemic effects in rat heart models. Its vasodilatory action has been demonstrated in various animal models, making it a valuable tool for studying the role of KATP channels in cardiovascular regulation. The compound's effects are mediated through its ability to cause membrane hyperpolarization in target tissues.
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| Enzyme Assay |
In cell-free enzymatic or receptor binding assays, Cromakalim's activity is typically evaluated using radioligand binding studies with [3H]glyburide or [3H]P1075 to determine its affinity for the sulfonylurea receptor (SUR) subunit of the KATP channel. Membrane preparations from tissues rich in KATP channels, such as cardiac or smooth muscle, are incubated with the radioligand and varying concentrations of Cromakalim. The displacement of the radioligand is measured to calculate the inhibition constant (Ki).
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| Cell Assay |
In vitro cell-based experiments with Cromakalim commonly involve isolated tissue bath studies. For example, rat aortic rings or other vascular smooth muscle preparations are pre-contracted with a vasoconstrictor like phenylephrine or KCl. Cumulative concentrations of Cromakalim are then added to the bath, and the resultant relaxation is measured isometrically. The concentration-response curve is generated to determine the compound's potency (EC50) and efficacy in inducing vasorelaxation.
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| Animal Protocol |
In vivo animal experiments typically involve normotensive or hypertensive rat models. Animals are administered Cromakalim via various routes (e.g., oral, intravenous, or intraperitoneal), and blood pressure is monitored using telemetry or tail-cuff methods. The compound's antihypertensive efficacy and duration of action are assessed. In cardioprotection studies, rat hearts are subjected to ischemia-reperfusion injury, and the effect of Cromakalim pretreatment on infarct size is evaluated.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Cromakalim have been characterized in preclinical studies. As a KATP channel opener, it is typically administered orally or intravenously. The compound is absorbed and distributed to target tissues, where it exerts its effects. Its half-life and bioavailability are dependent on the route of administration and the species studied. In general, Cromakalim displays favorable pharmacokinetic properties for a research compound, with good oral bioavailability and a moderate duration of action.
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| Toxicity/Toxicokinetics |
In preclinical toxicity studies, Cromakalim has been generally well-tolerated at therapeutic doses. As a vasodilator, its primary adverse effect is a dose-dependent reduction in blood pressure, which can lead to reflex tachycardia. No significant organ toxicity has been reported at concentrations used for research purposes. The compound is not intended for human therapeutic use and is strictly a research tool.
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| References | |
| Additional Infomation |
Levcromakalim is a 1-benzopyran compound. It is a potassium channel opener and vasodilator that has been investigated for the treatment of hypertension. It has also been used to treat asthma. (Martindale, Pharmacopoeia Supplement, 30th edition, p. 352)
Cromakalim is a prototypical KATP channel opener with a molecular formula of C16H18N2O3 and a molecular weight of 286.33. It is a racemic mixture, and its active enantiomer is levcromakalim. The compound has been instrumental in the discovery and development of newer KATP channel openers. It is not approved for clinical use but remains a critical reference standard for studying potassium channel pharmacology and cardiovascular physiology. It is available from various chemical suppliers for research purposes only. |
| Molecular Formula |
C16H18N2O3
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|---|---|
| Molecular Weight |
286.331
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| Exact Mass |
286.131
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| CAS # |
94470-67-4
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| PubChem CID |
93504
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
482.3±45.0 °C at 760 mmHg
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| Melting Point |
242-244ºC
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| Flash Point |
245.5±28.7 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.615
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| LogP |
1.27
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
21
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| Complexity |
481
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC1([C@H]([C@@H](C2=C(O1)C=CC(=C2)C#N)N3CCCC3=O)O)C
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| InChi Key |
TVZCRIROJQEVOT-CABCVRRESA-N
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| InChi Code |
InChI=1S/C16H18N2O3/c1-16(2)15(20)14(18-7-3-4-13(18)19)11-8-10(9-17)5-6-12(11)21-16/h5-6,8,14-15,20H,3-4,7H2,1-2H3/t14-,15+/m1/s1
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| Chemical Name |
(3S,4R)-3-hydroxy-2,2-dimethyl-4-(2-oxopyrrolidin-1-yl)-3,4-dihydrochromene-6-carbonitrile
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| Synonyms |
BRL34915; BRL-34915; BRL 34915
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
DMSO : ~66.67 mg/mL (~232.84 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (8.73 mM) (saturation unknown) 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. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (8.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4925 mL | 17.4624 mL | 34.9247 mL | |
| 5 mM | 0.6985 mL | 3.4925 mL | 6.9849 mL | |
| 10 mM | 0.3492 mL | 1.7462 mL | 3.4925 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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