| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
Levcromakalim targets ATP-sensitive potassium (KATP) channels, acting as a direct activator. KATP channels are inwardly rectifying potassium channels that couple cellular metabolism to membrane excitability. By opening these channels, levcromakalim increases potassium efflux, leading to hyperpolarization of the cell membrane. This reduces calcium influx through voltage-gated calcium channels, resulting in smooth muscle relaxation. The compound has an IC₅₀ of 490 nM in guinea pig trachea, confirming its potent relaxant activity.
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| ln Vitro |
In a glyburide-sensitive way, levcromakalim ((-)-Cromakalim) totally blocks autocontractions. Autoconstriction is inhibited by LevCromakalim (5 μM) and then recovered by glibenclamide. Autocontraction was suppressed by levcromakalim (1, 5 and 10 μM) to 34±21.1%, 20.1±20.0% and 0% of the control group (n = 5; P<0.05). Levcromakalim (20 and 100 μM) also inhibited the isometric contractions induced by oxytocin (OXT) (10 nM) Staged shrinkage to 34±21.4% and 14±12.6% of control (n=6 and 4, respectively; P<0.05). Glibenclamide restored the isometric contractions induced by LevCromakalim (5 μM) to 84±1.5% of control (n=5). LevCromakalim (100 μM) auto-isometric contraction transcription was reversed by glibudide to 79±3.5% of control (n=4; P<0.05). Additionally, glibenclamide-sensitive cromakalim reduced OXT's tetanic contraction [P < 0.05]. 2]. LevCromakalim (Cromakalim) is a specialized channel opener that is required for KATP channel operation. LevCromakalim causes stress contractions in both elderly and young persons' mesenteric arteries (MAs); age has no effect on the relaxing of the MAs. Nevertheless, an elderly MA's reaction (P<0.05) to a high-salt (HS) diet is dramatically decreased [3].
In vitro, levcromakalim acts as a KATP channel opener with an IC₅₀ of 490 nM in guinea pig trachea. It causes potent smooth muscle relaxation in isolated tissue preparations, including trachea and vascular smooth muscle. The compound's activity is confirmed through electrophysiological studies measuring KATP channel currents and through functional studies measuring muscle relaxation. |
| ln Vivo |
In vivo, levcromakalim has hypotensive and airways relaxant effects. It has been extensively studied for its potential therapeutic applications in hypertension, angina, and diabetes. The compound's vasodilator effects reduce blood pressure, and its bronchodilator effects relax airway smooth muscle. Detailed in vivo efficacy data from specific animal models are not extensively reported in the available literature.
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| Enzyme Assay |
Non-cell-based assays for levcromakalim typically involve patch-clamp electrophysiology using cells expressing KATP channels. The compound is applied to the cell, and KATP channel currents are measured. The compound's ability to activate KATP channels is quantified by measuring the increase in potassium current. Radioligand binding studies using [³H]-glibenclamide can also be performed to assess binding to the sulfonylurea receptor subunit of KATP channels.
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| Cell Assay |
Cellular assays for levcromakalim are performed using smooth muscle cells to assess relaxation. Cells are treated with the compound at various concentrations, and intracellular calcium levels are measured using fluorescent dyes. Membrane potential is measured using voltage-sensitive dyes or patch-clamp electrophysiology. The compound's ability to hyperpolarize cells and reduce calcium influx is quantified.
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| Animal Protocol |
In vivo animal models for levcromakalim include studies in hypertensive rats to assess blood pressure lowering effects. The compound is administered orally or intravenously, and blood pressure is measured using telemetry or tail-cuff methods. Airway relaxant effects are assessed in guinea pig models of bronchoconstriction. The compound's effects on insulin secretion and glucose metabolism are assessed in diabetic animal models.
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| ADME/Pharmacokinetics |
Levcromakalim has a molecular weight of 286.33 g/mol and a molecular formula of C₁₆H₁₈N₂O₃. CAS number is 94535-50-9. The compound is soluble in DMSO (≥50 mg/mL) but insoluble in water (<0.1 mg/mL). Purity is >98% by HPLC. Storage conditions: powder at -20°C. Detailed PK parameters such as half-life and bioavailability are not extensively reported in the available literature.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for levcromakalim are not extensively reported in the available literature. As a research compound, its safety profile would need to be established through standard preclinical toxicity assessments. The compound is supplied for research use only and is not for human consumption. Given its mechanism of KATP channel opening, potential side effects may include hypotension, tachycardia, and other cardiovascular effects.
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| References |
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| 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)
Levcromakalim is the active enantiomer of the prototypical KATP channel opener cromakalim. It is also known as (-)-Cromakalim and BRL-38227. The compound acts as a potent smooth muscle relaxant by directly activating ATP-sensitive K⁺ channels. It has hypotensive and airways relaxant effects, with an IC₅₀ of 490 nM in guinea pig trachea. Levcromakalim has been studied for potential applications in hypertension, angina, and diabetes. It is for research use only. |
| Molecular Formula |
C16H18N2O3
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| Molecular Weight |
286.331
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| Exact Mass |
286.132
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| CAS # |
94535-50-9
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| PubChem CID |
93504
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| Appearance |
White to off-white solid powder
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| Density |
1.31g/cm3
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| Boiling Point |
482.3ºC at 760mmHg
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| Flash Point |
245.5ºC
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| LogP |
1.691
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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 |
BRL 38227; Lemakalim; Levcromakalim
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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) |
DMSO : ≥ 50 mg/mL (~174.62 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% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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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