| Size | Price | Stock | Qty |
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| Targets |
SDZ-MKS 492 selectively targets type III isozyme cyclic nucleotide phosphodiesterase (PDE III). PDE III is one of 11 families of phosphodiesterases that hydrolyze cAMP and cGMP. PDE III is characterized by its high affinity for cAMP (Km ~0.1-1 microM) and its inhibition by cGMP. PDE III is expressed in various tissues including the heart, vascular smooth muscle, airway smooth muscle, and platelets. In the airways, PDE III inhibition leads to increased cAMP levels, which cause smooth muscle relaxation (bronchodilation), inhibition of mast cell degranulation, and reduced inflammatory cell activation. SDZ-MKS 492 specifically inhibits the PDE III isozyme, making it a valuable tool for studying the role of PDE III in airway function.
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| ln Vitro |
In vitro, MKS 492 relaxes smooth muscle in the airways [2].
In vitro, SDZ-MKS 492 inhibits PDE III activity, leading to increased intracellular cAMP levels. The compound shows selectivity for the type III isozyme of cyclic nucleotide phosphodiesterase. In cellular assays using airway smooth muscle cells, SDZ-MKS 492 causes concentration-dependent relaxation of pre-contracted tissues. The compound also inhibits antigen- and PAF-induced responses in isolated tissues. The mechanism of action involves elevation of cAMP, which activates PKA and leads to phosphorylation of downstream targets involved in smooth muscle relaxation and inflammatory suppression. |
| ln Vivo |
In guinea pigs, MKS-492 (3–10 mg/kg; intravenously) prevents bronchoconstriction caused by antigens [1]. In guinea pigs, PAF-induced bronchoconstriction and enhanced airway reactivity to histamine are inhibited by MKS-492 (1-3 mg/kg; intravenous injection) [1]. In guinea pigs, leukotriene B4 (LTB4)-induced airway eosinophilia is inhibited by MKS-492 (30-100 mg/kg; i.p.) [1]. In rats, MKS-492 (10–100 mg/kg; intraperitoneal injection) suppresses both medium-induced and passive skin allergy reactions [1].
In vivo, SDZ-MKS 492 inhibits antigen- or platelet-activating factor (PAF)-induced bronchoconstriction and anaphylaxis in guinea pigs and rats. In animal models of asthma, the compound reduces airway hyperresponsiveness, decreases bronchoconstriction, and attenuates inflammatory responses. PDE III inhibitors have been shown to be effective bronchodilators in preclinical models and in clinical settings for the treatment of asthma and chronic obstructive pulmonary disease (COPD). SDZ-MKS 492's efficacy in these models supports its potential as a therapeutic for respiratory disorders. |
| Enzyme Assay |
In vitro enzyme assays for SDZ-MKS 492 involve measuring PDE III activity using enzyme preparations from various tissues (e.g., cardiac or airway smooth muscle) or recombinant human PDE III enzyme. The assay is performed in 96-well plates using [3H]-cAMP as substrate. The enzyme is incubated with varying concentrations of SDZ-MKS 492 (0.001-100 microM) in assay buffer at 30degC for 10-20 minutes. The reaction is stopped by boiling or by adding a stop solution containing snake venom 5'-nucleotidase, which converts the 5'-AMP product to adenosine. The [3H]-adenosine is separated from [3H]-cAMP using ion-exchange resin or charcoal, and radioactivity is quantified by liquid scintillation counting. IC₅0 values are determined from dose-response curves. Selectivity is assessed against other PDE isozymes.
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| Cell Assay |
Cellular assays for SDZ-MKS 492 are performed using airway smooth muscle cells or lung tissue preparations. Cells are cultured in appropriate medium and seeded in 6- or 96-well plates. Cells are treated with SDZ-MKS 492 at concentrations of 0.01-100 microM for 15-60 minutes. Intracellular cAMP levels are measured using ELISA or HTRF-based detection kits. For functional assays, airway smooth muscle strips are mounted in organ baths and pre-contracted with histamine, acetylcholine, or other spasmogens. Cumulative concentration-response curves for relaxation are generated by adding SDZ-MKS 492. The potency (EC₅0) and efficacy of relaxation are determined. The role of cAMP elevation is confirmed by using PKA inhibitors.
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| Animal Protocol |
Animal/Disease Models: Passively sensitized female Hartley guinea pigs (250-300 g) with anti-BPO BGG guinea pig serum [1]
Doses: 3, 10 mg/kg Route of Administration: intravenous (iv) (iv)injection 5 minutes before antigen challenge Experimental Results: Inhibition of antigen-induced bromine Shrink in a dose-related manner. In vivo animal studies for SDZ-MKS 492 are conducted in guinea pig or rat models of bronchoconstriction and anaphylaxis. In guinea pig models, animals are sensitized with ovalbumin (OVA) and challenged with aerosolized OVA to induce bronchoconstriction. SDZ-MKS 492 is administered intravenously, orally, or by inhalation at doses of 0.1-10 mg/kg before antigen challenge. Airway resistance and dynamic compliance are measured using whole-body plethysmography or by recording pulmonary inflation pressure. In PAF-induced bronchoconstriction models, PAF is administered intravenously, and bronchoconstriction is measured. The compound's ability to inhibit bronchoconstriction and anaphylactic responses is quantified. Pharmacokinetic parameters are determined from plasma samples. |
| ADME/Pharmacokinetics |
SDZ-MKS 492 (CAS#: 114606-56-3) has molecular formula C20H2₇N₅O₆ and molecular weight 433.46. The chemical name is 8-{[(1R)-1-(3,4-dimethoxyphenyl)-2-hydroxyethyl]amino}-7-(2-methoxyethyl)-1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione. The compound is a selective type III isozyme cyclic nucleotide phosphodiesterase inhibitor. SDZ-MKS 492 inhibits antigen- or PAF-induced bronchoconstriction and anaphylaxis in guinea pigs and rats. The compound is a research chemical for laboratory use only. It is not for human therapeutic applications. The compound should be stored at -20degC, protected from light and moisture.
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| Toxicity/Toxicokinetics |
Toxicological information for SDZ-MKS 492 is limited as the compound is a research chemical. Based on its mechanism as a PDE III inhibitor, potential adverse effects may include cardiovascular effects (tachycardia, arrhythmias, hypotension), which are characteristic of PDE III inhibitors used clinically. The compound should be handled with standard laboratory precautions including the use of personal protective equipment and working in a well-ventilated area. Avoid inhalation, ingestion, and skin contact. The compound should be stored at -20degC and disposed of according to institutional guidelines for chemical waste.
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| References | |
| Additional Infomation |
SDZ-MKS 492 (CAS#: 114606-56-3), also known as MKS 492, is a selective type III cyclic nucleotide phosphodiesterase (PDE III) inhibitor. PDE III inhibitors increase intracellular cAMP levels and have bronchodilator, inotropic, and anti-inflammatory effects. SDZ-MKS 492 has been shown to inhibit antigen- or PAF-induced bronchoconstriction and anaphylaxis in guinea pigs and rats, supporting its potential for the treatment of asthma and other respiratory disorders. The compound is supplied for research use only and is not approved for clinical use. As of the current date, SDZ-MKS 492 remains a preclinical research compound.
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| Molecular Formula |
C20H27N5O6
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|---|---|
| Molecular Weight |
433.45828
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| Exact Mass |
433.196
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| CAS # |
114606-56-3
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| PubChem CID |
163931
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| Appearance |
White to off-white solid powder
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| LogP |
0.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
31
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| Complexity |
639
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| Defined Atom Stereocenter Count |
1
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| SMILES |
COCCN1C(NC(C2C=CC(OC)=C(OC)C=2)CO)=NC2N(C(N(C(=O)C1=2)C)=O)C
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| InChi Key |
VZLFAVFWNOZVFM-ZDUSSCGKSA-N
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| InChi Code |
InChI=1S/C20H27N5O6/c1-23-17-16(18(27)24(2)20(23)28)25(8-9-29-3)19(22-17)21-13(11-26)12-6-7-14(30-4)15(10-12)31-5/h6-7,10,13,26H,8-9,11H2,1-5H3,(H,21,22)/t13-/m0/s1
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| Chemical Name |
8-[[(1R)-1-(3,4-dimethoxyphenyl)-2-hydroxyethyl]amino]-7-(2-methoxyethyl)-1,3-dimethylpurine-2,6-dione
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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 (~115.35 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.80 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 20.8 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: ≥ 2.08 mg/mL (4.80 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 20.8 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: ≥ 2.08 mg/mL (4.80 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 | 2.3070 mL | 11.5351 mL | 23.0702 mL | |
| 5 mM | 0.4614 mL | 2.3070 mL | 4.6140 mL | |
| 10 mM | 0.2307 mL | 1.1535 mL | 2.3070 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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