CI-930
CI-930 is a selective, orally active phosphodiesterase 3 (PDE3) inhibitor with an IC50 value of 0.0.84 μM. CI-930 exerts positive inotropic and vasodilatory effects by inhibiting cAMP hydrolysis. CI-930 also regulates hemodynamics, inhibits the proliferation of coronary artery smooth muscle cells, and suppresses the proliferation of mouse splenocytes. CI-930 can be used in research related to heart failure, atherosclerosis, and asthma.
For research use only. We do not sell to patients.
- CAS No.: 86798-59-6
- Formula: C14H14N4O
- Molecular Weight:254.29
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[5]|
PDE3 |
In Vitro
CI-930 (0.10-100.00 μM; 10 min) significantly inhibits soluble PDE activity in human coronary artery smooth muscle cells (HCASMCs), reaching a maximum inhibition rate of approximately 43% at concentrations of 10-100 μM[3].
PDE3, the PDE isoform inhibited by CI-930 (10 μM), is expressed in both soluble and particulate fractions of quiescent HCASMCs, accounting for 42%-44% of total PDE activity[3].
CI-930 (10 μM) inhibits PDE3, a PDE that is expressed in both the soluble and particulate fractions of proliferative HCASMCs, accounting for 44%-45% of total PDE activity[3].
CI-930 (10-20 μM; 24-30 h) inhibits the proliferation of human coronary artery smooth muscle cells (HCASMCs): at a concentration of 10 μM, the proportion of S-phase cells decreases significantly by 33%; at a concentration of 20 μM, the proportion of S-phase cells also decreases significantly[3].
CI-930 (20 μM; 15-25 h) alone does not induce a statistically significant increase in cAMP levels in HCASMCs[3].
CI-930 (10 μM; 6 h) does not affect the steady-state level of IL-2 mRNA in human Jurkat leukemia T cells activated by PHA/PMA[4].
CI-930 (1 nM-10 μM; 72 h) inhibits Concanavalin A (Con A, HY-P2149, 2.5 μg/mL)-induced proliferation of mouse splenocytes with an IC50 of 4.4 μM, and results from MTT-based cell viability assays demonstrate that the inhibitory effect on cells is not caused by cell death[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:human coronary artery smooth muscle cells (HCASMC) from 32-year-old, 48-year-old, 58-year-old male donors, and a 61-year-old female donor
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Concentration:10 μM, 20 μM
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Incubation Time:24-30 h
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Result:Produced an 11-18% reduction in the percentage of cells in S phase across the three male donors, with a statistically significant reduction observed only in the 58-year-old male donor at 20 μM.
Produced a statistically significant 33% reduction in the percentage of cells in S phase in HCASMC from the 61-year-old female donor at 10 μM.
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Cell Line:human Jurkat leukemic T cells
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Concentration:10 μM
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Incubation Time:6 h
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Result:Showed unchanged steady-state levels of IL-2 mRNA in activated Jurkat cells, as confirmed by visualization of amplified PCR fragments and hybridization with a radiolabelled IL-2 probe.
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Cell Line:Concanavalin A-induced mouse splenocytes
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Concentration:10 μM, 1 μM, 0.1 μM, 30 nM, 1 nM
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Incubation Time:72 h
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Result:Inhibited concanavalin A-induced murine splenocyte proliferation with an IC50 of 4.4 μM.
MTT viability assay demonstrated that the antiproliferative effect was not due to cytotoxic cell death.
In Vivo
CI-930 (0.3-10 mg/kg; p.o.; twice daily) completely inhibits antigen-induced pulmonary eosinophilia and neutrophilia in Brown Norway rats, with ED50 values of 0.4 mg/kg and 0.5 mg/kg for twice-daily administration, respectively, showing comparable potency[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Brown Norway rats (male; 175-200 g at sensitization, 190-270 g at antigen challenge; allergic pulmonary inflammation model via ovalbumin sensitization and challenge with Bordetella pertussis adjuvant)[5]
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Dosage:0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:p.o.; B.I.D.
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Result:Significantly inhibited antigen-induced eosinophil influx at 0.3-3 mg/kg.
Completely inhibited eosinophil influx at 10 mg/kg.
Achieved a B.I.D.
ED50 of 0.4 mg/kg for eosinophil influx inhibition.
Significantly inhibited antigen-induced neutrophil influx at 1-10 mg/kg.
Completely inhibited neutrophil influx at 10 mg/kg.
Achieved a B.I.D.
ED50 of 0.5 mg/kg for neutrophil influx inhibition.
Chemical Information
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CAS No. 86798-59-6
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Molecular Weight 254.29
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Formula C14H14N4O
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SMILES
O=C1NN=C(C(C1)C)C2=CC=C(N3C=NC=C3)C=C2
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Research Protocol for Cardiovascular Diseases
Cardiovascular disease can be modeled as maladaptive cardiac remodeling, where ischemic injury or pressure overload activates inflammatory signaling, fibroblast activation, extracellular-matrix deposition, cardiomyocyte hypertrophy, vascular remodeling, and progressive ventricular dysfunction. The TGF-β/SMAD axis is a central profibrotic pathway after myocardial injury and pressure overload, while innate immune and cytokine pathways regulate leukocyte recruitment, scar formation, and adverse remodeling. Key unresolved questions include which inflammatory signals are reparative versus harmful, when fibrosis is protective versus maladaptive, and whether pathway inhibition improves function without weakening necessary infarct healing or compensatory remodeling.
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Purity & Documentation
References
[2]. Jafri SM, et al. Hemodynamic, Pharmacokinetic and Clinical Response to CI-930 in Congestive Heart Failure Due to Ischemic or Dilated Cardiomyopathy. The American Journal of Cardiology. 1987;59(11):1126-1130. [Content Brief]
[3]. Johnson-Mills K, et al. Effect of CI-930 [3-(2H)-pyridazinone-4,5-dihydro-6-[4-(1H-imidazolyl) phenyl]-5-methyl-monohydrochloride] and rolipram on human coronary artery smooth muscle cell proliferation. Biochemical pharmacology. 1998 Oct 15;56(8):1065-73. [Content Brief]
[4]. Lewis GM, et al. Effects of rolipram and CI-930 on IL-2 mRNA transcription in human Jurkat cells. Agents and actions. 1993;39 Spec No:C89-92. [Content Brief]
[5]. Howell RE, et al. Inhibition of antigen-induced pulmonary eosinophilia and neutrophilia by selective inhibitors of phosphodiesterase types 3 or 4 in Brown Norway rats. Pulmonary pharmacology. 1995;8(2-3):83-9. [Content Brief]
[6]. Gouault N et al. Solid-phase synthesis and evaluation of libraries of substituted 4,5-dihydropyridazinones as vasodilator agents. J Pharm Pharmacol. 2004 Aug;56(8):1029-37. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CI-930 Related Classifications
HY-183455 Related Classifications
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