Zaprinast (Synonyms: 2(oPropoxyphenyl)8azapurin6one, M&B 22,948) |
Katalog-Nr.GC12909
One-Click Copy Product Info
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Zaprinast (M&B 22948) ist ein Inhibitor cGMP-selektiver Phosphodiesterasen (PDEs).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 37762-06-4
Sample solution is provided at 25 µL, 10mM.
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Zaprinast is a phosphodiesterase inhibitor that targets PDE5 and PDE6, with the IC50 values of 0.8µM and 0.15µM, respectively[1]. Zaprinast acts as an agonist for rat GPR35, with a geometric mean EC50 value of 16nM[2]. Through inhibition of phosphodiesterases, especially PDE5 and PDE6, Zaprinast increases intracellular cGMP levels, which modulates downstream signaling pathways such as protein kinase G (PKG) and cyclic nucleotide gated ion channels[3]. Zaprinast has been widely used in different animal models to regulate smooth muscle contraction and coronary artery relaxation[4].
In vitro, Zaprinast treatment for 48 hours significantly inhibited SK-N-MC cell proliferation with an IC50 value of 3.3µM[5]. Zaprinast (100µM) treatment for 1 hour significantly activated ERK1/2, p38 MAPK, JNK, NFκB and PI3K/Akt signaling pathways in rat microglia[6]. Pretreatment of neonatal rat-derived astrocytes with 100μM Zaprinast for 1h significantly inhibited H2O2-induced lactate dehydrogenase release and cell death[7].
In vivo, Zaprinast treatment via intraperitoneal injection at a dose of 10mg/kg at 2 hours before and 24 and 48 hours after focal cryolesion of cortex significantly enhanced astrogliosis and reduced oxidative stress and cell death at 3 days after focal cryolesion in male Sprague-Dawley rats[8]. A single intraperitoneal injection of Zaprinast (30mg/kg) for 18 hours significantly improved glucose tolerance in diet-induced obese (DIO) mice[9].
References:
[1] Mackenzie A E, Milligan G. The emerging pharmacology and function of GPR35 in the nervous system[J]. Neuropharmacology, 2017, 113: 661-671.
[2] Taniguchi Y, Tonai-Kachi H, Shinjo K. Zaprinast, a well-known cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, is an agonist for GPR35[J]. FEBS letters, 2006, 580(21): 5003-5008.
[3] Halene T B, Siegel S J. PDE inhibitors in psychiatry–future options for dementia, depression and schizophrenia?[J]. Drug discovery today, 2007, 12(19-20): 870-878.
[4] Gibson A. Phosphodiesterase 5 inhibitors and nitrergic transmission—from zaprinast to sildenafil[J]. European journal of pharmacology, 2001, 411(1-2): 1-10.
[5] Giorgi M, Leonetti C, Citro G, et al. In vitro and in vivo inhibition of SK-N-MC neuroblastoma growth using cyclic nucleotide phosphodiesterase inhibitors[J]. Journal of neuro-oncology, 2001, 51(1): 25-31.
[6] Lee H S, Kwon S H, Ham J E, et al. Zaprinast activates MAPKs, NFκB, and Akt and induces the expressions of inflammatory genes in microglia[J]. International immunopharmacology, 2012, 13(3): 232-241.
[7] Choi J H, Kim D H, Yun I J, et al. Zaprinast inhibits hydrogen peroxide-induced lysosomal destabilization and cell death in astrocytes[J]. European journal of pharmacology, 2007, 571(2-3): 106-115.
[8] Pifarré P, Prado J, Giralt M, et al. Cyclic GMP phosphodiesterase inhibition alters the glial inflammatory response, reduces oxidative stress and cell death and increases angiogenesis following focal brain injury[J]. Journal of neurochemistry, 2010, 112(3): 807-817.
[9] Hodges W T, Jarasvaraparn C, Ferguson D, et al. Mitochondrial pyruvate carrier inhibitors improve metabolic parameters in diet-induced obese mice[J]. Journal of Biological Chemistry, 2022, 298(2): 101554.
| Cell experiment [1]: | |
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Cell lines |
SK-N-MC cells |
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Preparation Method |
SK-N-MC cells were cultured in Minimum Essential Medium (MEM) supplemented with non-essential amino acid (NEAA), sodium pyruvate (110mg/l), 10% foetal bovine serum, penicillin (5000IU/ml) and streptomycin (5mg/ml), at 37℃ in a humidified 5% CO2 atmosphere. Cultures were periodically tested for mycoplasma contamination and only negative cells were used for experiments. Cells were plated in 24-well trays at a density of 5×104 cells/well. Twenty-four hours later, Zaprinast was added at various concentration (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, and 5µM). Forty-eight hours later the number of surviving cells was determined. |
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Reaction Conditions |
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, and 5µM; 48h |
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Applications |
Zaprinast treatment inhibited the cell viability of SK-N-MC cells in a dose-dependent manner. |
| Animal experiment [2]: | |
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Animal models |
LS-Mpc2−/− mice |
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Preparation Method |
LS-Mpc2−/− mice were raised in a standard sterile environment, switched from standard diet to 60% high-fat diet at 7 to 8 weeks of age and tested 12 weeks later. Zaprinast was dissolved in 25% DMSO/75% saline and administered intraperitoneally at a dose of 30mg/kg 18 hours before the glucose tolerance test (GTT). |
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Dosage form |
30mg/kg for once; i.p. |
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Applications |
Zaprinast treatment significantly improved glucose tolerance in LS-Mpc2−/− mice. |
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References: |
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| Cas No. | 37762-06-4 | SDF | |
| Überlieferungen | 2(oPropoxyphenyl)8azapurin6one, M&B 22,948 | ||
| Chemical Name | 5-(2-propoxyphenyl)-2H-[1,2,3]triazolo[4,5-d]pyrimidin-7(3H)-one | ||
| Canonical SMILES | O=C1N=C(C2=CC=CC=C2OCCC)N=C3NNN=C31 | ||
| Formula | C13H13N5O2 | M.Wt | 271.28 |
| Löslichkeit | DMF: 20 mg/ml,DMF:PBS(pH 7.2)(1:1): 0.5 mg/ml,DMSO: 10 mg/ml | Storage | Store at -20°C, protect from light, stored under nitrogen |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.6862 mL | 18.4311 mL | 36.8623 mL |
| 5 mM | 737.2 μL | 3.6862 mL | 7.3725 mL |
| 10 mM | 368.6 μL | 1.8431 mL | 3.6862 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 9 reference(s) in Google Scholar.)