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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
Phosphodiesterase 2 (PDE2) and phosphodiesterase 3 (PDE3), enzymes that hydrolyze cyclic nucleotides (cAMP and cGMP). Carbazeran is an inhibitor of PDE2 and PDE3. It inhibits cAMP hydrolysis (IC50 = 4.1 µM in rabbit heart ventricles) selectively over cGMP hydrolysis (IC50 = 171 µM). The compound is also a potent inhibitor of PDE-II and PDE-III.
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| ln Vitro |
Carbazeran inhibits PDE2 and PDE3, blocking the hydrolysis of cyclic nucleotides (cAMP and cGMP). The compound inhibits cAMP hydrolysis with an IC50 of 4.1 µM in rabbit heart ventricles, selectively over cGMP hydrolysis (IC50 = 171 µM). Carbazeran shows inotropic and chronotropic effects in vivo (EC50 = 100 µM, inotropic effects, independent of adrenergic mechanisms). The compound is also a substrate for aldehyde oxidase (AO), leading to rapid metabolism in humans.
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| ln Vivo |
In vivo, carbazeran shows chronotropic and inotropic effects (EC50 = 100 µM for inotropic effects, independent of adrenergic mechanisms). The compound's positive inotropic effects are mediated through PDE inhibition, leading to increased cAMP levels and enhanced cardiac contractility. Carbazeran's rapid metabolism in humans (via aldehyde oxidase) limits its clinical utility. The compound has been studied in the context of metabolic diseases.
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| Enzyme Assay |
In vitro enzyme assays for carbazeran involve measuring PDE2 and PDE3 inhibition using radiometric or fluorogenic methods. The enzymes are incubated with cAMP or cGMP substrates and various concentrations of carbazeran, and the hydrolysis of cyclic nucleotides is measured. IC50 values are determined from concentration-response curves. Carbazeran inhibits cAMP hydrolysis with an IC50 of 4.1 µM and cGMP hydrolysis with an IC50 of 171 µM.
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| Cell Assay |
Cellular assays for carbazeran involve treating cells with the compound and measuring changes in cAMP or cGMP levels using ELISA or other methods. The compound's ability to inhibit PDE activity and increase cyclic nucleotide levels is demonstrated in these assays. Carbazeran's effects on cellular signaling pathways regulated by PDEs can be studied using these approaches.
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| Animal Protocol |
In vivo animal studies for carbazeran typically involve administration to rodents or other species to assess its cardiovascular effects (chronotropic and inotropic effects). The compound's metabolism by aldehyde oxidase can be studied using animal models, and the impact of metabolic differences between species on the compound's pharmacokinetics and efficacy can be evaluated.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies of carbazeran have shown that the compound is a substrate for aldehyde oxidase (AO), leading to rapid metabolism in humans. This rapid metabolism limits its clinical utility. In animal studies, the mean plasma concentrations were lower than in those from control mice for 0.5-4 hours after oral administration. The compound's pharmacokinetic profile is influenced by species differences in aldehyde oxidase activity.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies of carbazeran are limited. The compound's primary limitation for clinical development is its rapid metabolism by aldehyde oxidase in humans, which leads to short half-life and reduced efficacy. Toxicity studies would be needed to evaluate the safety of the compound and its metabolites.
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| References | |
| Additional Infomation |
Carbazeran (UK-31,557) is a potent inhibitor of PDE2 and PDE3 with inotropic and chronotropic effects. The compound inhibits cAMP hydrolysis with an IC50 of 4.1 µM in rabbit heart ventricles. Carbazeran is also a substrate for aldehyde oxidase (AO), leading to rapid metabolism in humans which limits its clinical utility. The compound may be used for studies about metabolic diseases.
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| Molecular Formula |
C18H24N4O4
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|---|---|
| Molecular Weight |
360.41
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| Exact Mass |
360.179
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| CAS # |
70724-25-3
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| Related CAS # |
Carbazeran citrate;153473-94-0
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| PubChem CID |
71983
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
595.6±50.0 °C at 760 mmHg
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| Flash Point |
314.0±30.1 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.600
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| LogP |
1.38
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
26
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| Complexity |
459
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
QJGVXJYGDBSPSJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H24N4O4/c1-4-19-18(23)26-13-5-7-22(8-6-13)17-14-10-16(25-3)15(24-2)9-12(14)11-20-21-17/h9-11,13H,4-8H2,1-3H3,(H,19,23)
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| Chemical Name |
[1-(6,7-dimethoxyphthalazin-1-yl)piperidin-4-yl] N-ethylcarbamate
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| Synonyms |
UK-31557 UK 31557 Carbazeran
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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 : ≥ 125 mg/mL (~346.83 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 | 2.7746 mL | 13.8731 mL | 27.7462 mL | |
| 5 mM | 0.5549 mL | 2.7746 mL | 5.5492 mL | |
| 10 mM | 0.2775 mL | 1.3873 mL | 2.7746 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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