| Size | Price | Stock | Qty |
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| 100mg |
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| Other Sizes |
| Targets |
Meticrane targets multiple proteins and receptors, contributing to its diverse pharmacological profile. Its primary target is the sodium-chloride symporter (NCC/SLC12A3) in the distal convoluted tubule, where it inhibits ion reabsorption. Meticrane also functions as a potent inhibitor of the peripheral-type benzodiazepine receptor (PBR/TSPO) with an IC50 of 1 μM. In addition, meticrane inhibits carbonic anhydrase (CA) isoforms, including CAVB, VII, IX, XII, and XIII, with Ki values ranging from 2.8 to 23 nM. It shows weaker inhibition of CAI, CAII, IV, VA, and VI, with Ki values of 138-1,347 nM. This carbonic anhydrase inhibition may mediate its sustained vasodilatory activity. Meticrane also targets human thrombin (F2), estrogen receptor alpha (ESR1), and progesterone receptor (PGR). Its dual properties as a diuretic and PBR inhibitor contribute to its pharmacological profile and potential applications in conditions related to fluid balance and the modulation of PBR-mediated pathways.
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| ln Vitro |
In vitro studies have demonstrated that meticrane exhibits significant activity at various molecular targets. The compound shows potent inhibition of carbonic anhydrase isoforms, with Ki values ranging from 2.8 to 23 nM for CAVB, VII, IX, XII, and XIII. It is also a potent inhibitor of the peripheral-type benzodiazepine receptor (PBR) with an IC50 of 1 μM. In cellular models, meticrane has been investigated for its potential anticancer activity. Studies have shown that meticrane, a non-oncology drug, exhibits anticancer potential when used in combination with epigenetic inhibitors in vitro. The compound's effects on ion transport can be studied in renal epithelial cell lines, where its inhibition of sodium and chloride reabsorption can be measured directly. Meticrane has also been evaluated in connectivity map (cMap) analysis, where it is highly ranked among thiazide diuretics. In addition to its diuretic and carbonic anhydrase inhibitory activities, meticrane has been shown to have no known anti-cancer or immune-stimulating effects when used alone.
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| ln Vivo |
Meticrane is a thiazide diuretic with no known immunostimulatory or anticancer properties that ranks highly in connectivity map (cMap) analysis. The therapeutic benefit of CTLA-4 blockage can be greatly increased by combined treatment with meticrane [2].
In vivo, meticrane demonstrates diuretic activity through its action on the distal convoluted tubule. The compound promotes the increased excretion of urine by inhibiting the reabsorption of sodium and chloride ions. This leads to increased urine production and a reduction in blood volume and pressure. The diuretic effect of meticrane is dose-dependent, with greater inhibition of ion reabsorption at higher concentrations. The compound's activity as a peripheral-type benzodiazepine receptor inhibitor may also contribute to its overall pharmacological effects. Meticrane's dual properties as a diuretic and PBR inhibitor make it a unique tool for studying both fluid balance and PBR-mediated pathways. The compound has been studied in the context of essential hypertension, where its diuretic effects contribute to blood pressure reduction. Despite its efficacy, meticrane is marketed solely in Japan, and its use is limited to specific regions. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for meticrane employ a variety of techniques depending on the target of interest. For carbonic anhydrase inhibition, assays typically measure the rate of CO₂ hydration or p-nitrophenyl acetate hydrolysis catalyzed by the enzyme. The compound is incubated with the enzyme and substrate, and activity is calculated from absorbance changes over time. Inhibition constants (Ki) are determined from dose-response curves. For peripheral-type benzodiazepine receptor binding, radioligand displacement assays are used, employing [³H]-PK11195 or similar radioligands with membrane preparations from tissues or cells expressing the receptor. The compound is incubated with membranes and radioligand, and bound radioactivity is measured by scintillation counting. For sodium-chloride symporter inhibition, assays may use membrane vesicles or cells expressing the transporter, with ion flux measurements using radioisotopes or ion-sensitive electrodes. Thrombin inhibition assays measure the cleavage of chromogenic substrates in the presence of the compound. Estrogen receptor and progesterone receptor binding can be assessed using radioligand displacement or fluorescence polarization methods.
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| Cell Assay |
Cellular assays for meticrane typically employ renal epithelial cell lines to evaluate its effects on ion transport and diuretic activity. Cells such as MDCK or LLC-PK1, which express sodium-chloride symporters, are cultured in appropriate media and treated with meticrane at varying concentrations. Ion flux is measured using fluorescent indicators or radioisotopes to assess sodium and chloride transport across cell membranes. The compound's effects on cell viability and proliferation can be assessed using standard cytotoxicity assays such as MTT or resazurin reduction. In cancer research applications, meticrane has been studied in combination with epigenetic inhibitors to evaluate its anticancer potential. Cellular models of cancer, including various cancer cell lines, are treated with meticrane alone or in combination with other agents, and cell proliferation, apoptosis, and signaling pathways are assessed. The compound's effects on PBR-mediated signaling can be studied in cells expressing the receptor, with readouts including changes in mitochondrial function, steroidogenesis, or apoptosis.
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| Animal Protocol |
In vivo animal experiments for meticrane typically employ rodent models to evaluate its diuretic and antihypertensive effects. Rats or mice are administered meticrane via oral gavage or intraperitoneal injection at various doses. Diuretic activity is assessed by measuring urine output and electrolyte excretion over a defined period. Animals are typically housed in metabolic cages to allow for accurate collection of urine samples. Blood pressure measurements are taken using tail-cuff plethysmography or telemetry to evaluate the compound's antihypertensive effects. For studies investigating carbonic anhydrase inhibition, animal models of glaucoma or elevated intraocular pressure may be used, with intraocular pressure measured using tonometry. The compound's effects on fluid balance and electrolyte homeostasis are assessed by measuring serum electrolyte levels and hematocrit. For studies exploring potential anticancer activity, xenograft models may be employed, with tumor growth measured following meticrane treatment. Dosing regimens vary depending on the experimental objectives, with acute studies using single doses and chronic studies using repeated daily administration.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of meticrane are characteristic of thiazide-like diuretics. The compound is administered orally and is absorbed from the gastrointestinal tract. It acts primarily in the kidney, where it inhibits ion reabsorption in the distal convoluted tubule. The compound's molecular weight is 275.34, and it has a molecular formula of C₁₀H₁₃NO₄S₂. Meticrane exhibits good solubility in appropriate solvents for formulation. The compound's pharmacokinetic profile in terms of absorption, distribution, metabolism, and excretion is consistent with its use as an oral diuretic. As with other thiazide-like diuretics, meticrane is expected to be excreted primarily in the urine. The compound's carbonic anhydrase inhibitory activity may influence its distribution and elimination. Studies on the compound's stability in solution have been limited, and general guidelines for storage and handling are typically followed. The compound's oral bioavailability and half-life are consistent with once-daily or twice-daily dosing for hypertension management.
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| Toxicity/Toxicokinetics |
The toxicity profile of meticrane is consistent with that of thiazide-like diuretics. Common adverse effects may include electrolyte imbalances, particularly hypokalemia, hyponatremia, and hypochloremia, resulting from increased urinary excretion of these ions. Other potential adverse effects include hyperglycemia, hyperuricemia, and lipid abnormalities, which are characteristic of thiazide diuretics. The compound's carbonic anhydrase inhibitory activity may contribute to metabolic acidosis at higher doses. Meticrane has been studied for its potential anticancer activity, and studies have shown that it exhibits anticancer potential when used in combination with epigenetic inhibitors in vitro. However, the compound does not have any known anti-cancer or immune-stimulating effect when used alone. The toxicity of meticrane at therapeutic doses is generally manageable, and the compound has been used clinically for the treatment of essential hypertension. As with all diuretics, careful monitoring of electrolyte levels and renal function is recommended during therapy. The compound's safety profile in special populations, such as patients with renal impairment or hepatic dysfunction, should be considered.
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| References | |
| Additional Infomation |
Meticrane is a sulfonamide compound. It is a diuretic. In Japan, it is marketed under the brand name Arresten and used to lower blood pressure. Meticrane is a sulfonamide derivative with the activity of thiazide diuretics. Its mechanism of action is similar to that of thiazide diuretics.
Meticrane is a sulphonamide-derivative thiazide-like diuretic classified under ATC code C03BA09. It is used for the treatment of essential hypertension and acts by inhibiting the reabsorption of sodium and chloride ions in the distal convoluted tubule. The compound is marketed solely in Japan under various trade names, including Fontiliz and Arresten. Meticrane is also recognized as a potent inhibitor of the peripheral-type benzodiazepine receptor (PBR) with an IC50 of 1 μM. The compound exhibits carbonic anhydrase inhibitory activity, particularly against isoforms CAVB, VII, IX, XII, and XIII, with Ki values of 2.8-23 nM. This carbonic anhydrase inhibition may mediate its sustained vasodilatory activity. Meticrane has a molecular weight of 275.34 and a molecular formula of C₁₀H₁₃NO₄S₂. It is highly ranked in connectivity map (cMap) analysis and does not have any known anti-cancer or immune-stimulating effect when used alone. However, studies have shown that meticrane exhibits anticancer potential when used in combination with epigenetic inhibitors in vitro. The compound's dual properties as a diuretic and PBR inhibitor contribute to its pharmacological profile and potential applications in conditions related to fluid balance and the modulation of PBR-mediated pathways. |
| Molecular Formula |
C10H13NO4S2
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|---|---|
| Molecular Weight |
275.34452
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| Exact Mass |
275.029
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| CAS # |
1084-65-7
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| PubChem CID |
4165
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| Appearance |
White to off-white solid powder
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| Density |
1.464g/cm3
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| Boiling Point |
549.1ºC at 760mmHg
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| Melting Point |
236-237°
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| Flash Point |
285.9ºC
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| Vapour Pressure |
4.16E-12mmHg at 25°C
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| Index of Refraction |
1.601
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| LogP |
3.224
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
17
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| Complexity |
485
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
FNQQBFNIYODEMB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H13NO4S2/c1-7-5-8-3-2-4-16(12,13)10(8)6-9(7)17(11,14)15/h5-6H,2-4H2,1H3,(H2,11,14,15)
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| Chemical Name |
6-methyl-1,1-dioxo-3,4-dihydro-2H-thiochromene-7-sulfonamide
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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 (~181.59 mM)
H2O : ~0.1 mg/mL (~0.36 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.08 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 (9.08 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 (9.08 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 | 3.6319 mL | 18.1594 mL | 36.3187 mL | |
| 5 mM | 0.7264 mL | 3.6319 mL | 7.2637 mL | |
| 10 mM | 0.3632 mL | 1.8159 mL | 3.6319 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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