| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
YM976 is a novel and selective inhibitor of phosphodiesterase type 4 (PDE4). It is a competitive inhibitor of the PDE4 enzyme. In a cell-free assay, its IC50 for inhibiting PDE4 activity is 2.2 nM [1].
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| ln Vitro |
Effect on Tracheal Smooth Muscle Tension: In bovine tracheal smooth muscle preparations precontracted with 3 μM or 100 μM histamine, YM976 (0.1 nM to 10 μM) induces a concentration-dependent relaxation. The pIC50 values (negative logarithm of the molar concentration required to decrease histamine-induced tension by 50%) are 7.14 ± 0.09 against 3 μM histamine and 6.23 ± 0.11 against 100 μM histamine. The relaxant effect is significantly reduced when the preparation is precontracted with 0.1 μM methacholine instead of histamine [1].
Preventive Effect on Contraction: Pretreatment of bovine tracheal smooth muscle with 10 μM YM976 for 10-15 minutes significantly shifts the concentration-response curve for histamine-induced contractions to the right, reducing the pEC50 for histamine from 4.96 ± 0.06 to 4.62 ± 0.05, without affecting the maximal response. At 0.1 μM, YM976 does not significantly affect the pEC50 for histamine. Pretreatment with 10 μM YM976 does not shift the concentration-response curve for methacholine-induced contractions [1]. cAMP Accumulation: YM976 (10 μM) causes a time-dependent increase in cAMP content in bovine tracheal smooth muscle, reaching a steady state 5-15 minutes after addition. The cAMP accumulation induced by YM976 is concentration-dependent. At 0.1, 1, and 10 μM, YM976 increases tissue cAMP content, with 10 μM producing a significant increase comparable to that of 10 μM rolipram [1]. |
| Enzyme Assay |
PDE4 Inhibitory Activity Assay: The inhibitory effect of YM976 on phosphodiesterase 4 (PDE4) activity was determined in a cell-free experiment using PDE4 enzyme isolated from human monocytic cells. The compound was shown to be a strong and competitive inhibitor of PDE4. Its inhibitory effect (IC50 = 2.2 nM) was approximately 400-fold stronger than that of rolipram (IC50 = 820 nM) [1].
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| Animal Protocol |
Ex Vivo Tracheal Smooth Muscle Relaxation Protocol:** Bovine tracheas were obtained from a local abattoir. Smooth muscle segments (1×2×10 mm) were dissected and mounted in 20-ml organ baths containing Krebs-Ringer bicarbonate buffer (pH 7.4) gassed with 95% O₂-5% CO₂ at 37°C. Tissues were equilibrated for 2 hours under an initial tension of 0.75 g. To assess reversal effects, preparations were precontracted with either histamine (3 or 100 μM) or methacholine (0.1 μM). After confirming a plateau, YM976 (0.1 nM to 10 μM), rolipram, or theophylline was added cumulatively. To assess preventive effects, tissues were pre-incubated with YM976 (0.1 or 10 μM) or its solvent for 10-15 minutes before the cumulative addition of histamine (0.1 μM to 10 mM) or methacholine (0.3 nM to 300 μM). Tension was recorded isometrically [1].
Ex Vivo Tracheal Smooth Muscle Relaxation Protocol: Bovine tracheas were obtained from a local abattoir. Smooth muscle segments (1×2×10 mm) were dissected and mounted in 20-ml organ baths containing Krebs-Ringer bicarbonate buffer (pH 7.4) gassed with 95% O₂-5% CO₂ at 37°C. Tissues were equilibrated for 2 hours under an initial tension of 0.75 g. To assess reversal effects, preparations were precontracted with either histamine (3 or 100 μM) or methacholine (0.1 μM). After confirming a plateau, YM976 (0.1 nM to 10 μM), rolipram, or theophylline was added cumulatively. To assess preventive effects, tissues were pre-incubated with YM976 (0.1 or 10 μM) or its solvent for 10-15 minutes before the cumulative addition of histamine (0.1 μM to 10 mM) or methacholine (0.3 nM to 300 μM). Tension was recorded isometrically [1]. |
| Toxicity/Toxicokinetics |
The provided literature does not contain direct experimental data on the toxicity of YM976. It mentions that other PDE4 inhibitors have adverse actions such as nausea and vomiting, and that YM976 was developed as a PDE4 inhibitor with little or no emetic effect, but no specific toxicity data for YM976 is presented in this paper [1].
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| References | |
| Additional Infomation |
4-(3-chlorophenyl)-1,7-diethyl-2-pyrido[2,3-d]pyrimidinone is a member of the pyrimidine class of compounds.
YM976 (4-(3-chlorophenyl)-1,7-diethylpyrido[2,3-d]pyrimidin-2(1H)-one) is a novel PDE4 inhibitor with a chemical structure totally different from existing inhibitors like rolipram, as it lacks the 3-cyclopentyloxy-4-methoxyphenyl group. It was developed with the aim of having little or no emetic side effects. The compound relaxes tracheal smooth muscle precontracted with histamine, an effect that is likely mediated by the accumulation of intracellular cAMP resulting from PDE4 inhibition. Its relaxant effect is less potent than rolipram at lower concentrations (<1 μM) but becomes comparable at higher concentrations (3-10 μM). The compound is more effective against contractions induced by histamine than against those induced by methacholine. Based on references cited within the paper, YM976 has been shown to inhibit inflammatory cell functions (such as cytokine production, superoxide formation, and chemotaxis) at nanomolar concentrations, and to prevent antigen-induced bronchoconstriction and airway hyperreactivity in vivo, suggesting its potential as a candidate for treating inflammatory diseases like bronchial asthma [1]. |
| Molecular Formula |
C17H16CLN3O
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|---|---|
| Molecular Weight |
313.79
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| Exact Mass |
313.098
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| CAS # |
191219-80-4
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| PubChem CID |
6604918
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| Appearance |
White to off-white solid powder
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| Density |
1.27g/cm3
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| Boiling Point |
485.4ºC at 760mmHg
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| Melting Point |
132.7-134.0ºC(lit.)
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| Flash Point |
247.4ºC
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| Vapour Pressure |
1.42E-09mmHg at 25°C
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| Index of Refraction |
1.638
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| LogP |
3.694
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
22
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| Complexity |
453
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
MNHXYNNKDDXKNP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H16ClN3O/c1-3-13-8-9-14-15(11-6-5-7-12(18)10-11)20-17(22)21(4-2)16(14)19-13/h5-10H,3-4H2,1-2H3
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| Chemical Name |
4-(3-chlorophenyl)-1,7-diethylpyrido[2,3-d]pyrimidin-2-one
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| Synonyms |
YM976 YM-976 YM 976
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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, avoid exposure to moisture. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 3.1868 mL | 15.9342 mL | 31.8684 mL | |
| 5 mM | 0.6374 mL | 3.1868 mL | 6.3737 mL | |
| 10 mM | 0.3187 mL | 1.5934 mL | 3.1868 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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