Quazinone
(Synonyms: 快嗪酮) 目录号 : GC45903A PDE3 inhibitor
Cas No.:70018-51-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Quazinone is a selective inhibitor of phosphodiesterase 3 (PDE3) with positive inotropic and vasodilating properties.1,2 It induces relaxation of precontracted isolated human cavernous smooth muscle (IC50 = 4.2 μM).1 Quazinone (10-300 μg/kg) increases myocardial contractile force in anesthetized open-chest dogs in a dose-dependent manner, as well as decreases systolic and diastolic blood pressure.2 It also inhibits DNA synthesis induced by the PDGF isoform PDGF-BB in bovine coronary artery smooth muscle cells in a concentration-dependent manner.3
|1. Taher, A., Meyer, M., Stief, C.G., et al. Cyclic nucleotide phosphodiesterase in human cavernous smooth muscle. World J. Urol. 15(1), 32-35 (1997).|2. Eigenmann, R., Gerold, M., and Holck, M. Cardiovascular profile of Ro 13-6438, a novel positive inotropic agent with vasodilating properties. J. Cardiovasc. Pharmacol. 6(3), 511-519 (1984).|3. Osinski, M.T., and Schr•r, K. Inhibition of platelet-derived growth factor-induced mitogenesis by phosphodiesterase 3 inhibitors: Role of protein kinase A in vascular smooth muscle cell mitogenesis. Biochem. Pharmacol. 60(3), 381-387 (2000).
| Cas No. | 70018-51-8 | SDF | |
| 别名 | 快嗪酮 | ||
| Canonical SMILES | ClC1=C2C(NC(N3C2)=NC([C@H]3C)=O)=CC=C1 | ||
| 分子式 | C11H10ClN3O | 分子量 | 235.7 |
| 溶解度 | DMSO: 5 mg/ml,Ethanol: 1 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.2427 mL | 21.2134 mL | 42.4268 mL |
| 5 mM | 0.8485 mL | 4.2427 mL | 8.4854 mL |
| 10 mM | 0.4243 mL | 2.1213 mL | 4.2427 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Targeting tumor cells based on Phosphodiesterase 3A expression
Exp Cell Res 2017 Dec 15;361(2):308-315.PMID:29107068DOI:10.1016/j.yexcr.2017.10.032.
We and others have previously reported a correlation between high phosphodiesterase 3A (PDE3A) expression and selective sensitivity to phosphodiesterase (PDE) inhibitors. This indicates that PDE3A could serve both as a drug target and a biomarker of sensitivity to PDE3 inhibition. In this report, we explored publicly available mRNA gene expression data to identify cell lines with different PDE3A expression. Cell lines with high PDE3A expression showed marked in vitro sensitivity to PDE inhibitors zardaverine and Quazinone, when compared with those having low PDE3A expression. Immunofluorescence and immunohistochemical stainings were in agreement with PDE3A mRNA expression, providing suitable alternatives for biomarker analysis of clinical tissue specimens. Moreover, we here demonstrate that tumor cells from patients with ovarian carcinoma show great variability in PDE3A protein expression and that level of PDE3A expression is correlated with sensitivity to PDE inhibition. Finally, we demonstrate that PDE3A is highly expressed in subsets of patient tumor cell samples from different solid cancer diagnoses and expressed at exceptional levels in gastrointestinal stromal tumor (GIST) specimens. Importantly, vulnerability to PDE3 inhibitors has recently been associated with co-expression of PDE3A and Schlafen family member 12 (SLFN12). We here demonstrate that high expression of PDE3A in clinical specimens, at least on the mRNA level, seems to be frequently associated with high SLFN12 expression. In conclusion, PDE3A seems to be both a promising biomarker and drug target for individualized drug treatment of various cancers.
Modulation of neurotransmitter release by carbon monoxide at the frog neuro-muscular junction
Curr Drug Metab 2007 Feb;8(2):177-84.PMID:17305496DOI:10.2174/138920007779815940.
Carbon monoxide (CO) is an endogenous gaseous messenger, which regulates numerous physiological functions in a wide variety of tissues. Using extracellular microelectrode recording from frog neuro-muscular preparation the mechanisms of exogenous and endogenous CO action on evoked quantal acetyl-choline (Ach) release were studied. It was shown that CO application increases Ach-release in dose-dependent manner without changes in pre-synaptic Na+ and K+ currents. The effect of exogenous CO on Ach-release was decreased by prior application of guanylate cyclase inhibitor ODQ and prevented by application of a cyclic guanylate monophosphate (cGMP) analog 8Br-cGMP. Pre-treatment of the preparation with adenylate cyclase inhibitor MDL-12330A has completely abolished the effect of CO, whereas elevation of intracellular level of cyclic adenosine monophosphate (cAMP) mimicked and eliminated CO action. Application of cGMP-activated phosphodiesterase-2 inhibitor EHNA did not prevent CO action, whereas inhibition of cGMP-inhibited phosphodiesterase-3 by Quazinone has partially blocked the effect of CO. Utilizing immuno-histochemical methods CO-producing enzyme heme-oxygenase-2 (HO-2) was shown to be expressed in skeletal muscle fibers, mostly in sub-sarcolemmal region, karyolemma and sarcoplasmic reticulum. Zn-protoporphirin-IX, the selective HO-2 blocker, has depressed Ach-release, suggesting the tonic activating effect of endogenous CO on pre-synaptic function. These results suggest that facilitatory effect of CO on Ach-release is mediated by elevation of intracellular cAMP level due to activation of adenylate cyclase and decrease of cAMP breakdown. As such, endogenous skeletal muscle-derived CO mediates tonic retrograde up-regulation of neuro-transmitter release at the frog neuro-muscular junction.
Phosphodiesterase isoenzymes in human ureteral smooth muscle: identification, characterization, and functional effects of various phosphodiesterase inhibitors in vitro
Urol Int 1995;55(4):183-9.PMID:8588263DOI:10.1159/000282783.
Phosphodiesterases (PDE) are key enzymes regulating intracellular cyclic nucleotide metabolism and, thus, contraction and relaxation of the muscle. At present, five different families of isoenzymes of PDE exist that show a distinct species-specific and organ-specific distribution. The aim of the present study was to analyze the PDE isoenzymes present in the human ureter and to evaluate the functional effects of isoenzyme-specific inhibitors in this tissue. Normal ureteral tissue was obtained during radical nephrectomies, homogenized, centrifuged, and the supernatant fraction was separated using DEAE-Sephacel anion-exchange chromatography. PDE assay was then performed and the isoenzymes characterized on the basis of their kinetic characteristics and their sensitivity to allosteric modulators and inhibitors. In vitro, longitudinal ureteral strips as well as ureteral rings were precontracted, and different selective and nonselective PDE inhibitors were added incrementally. Three different PDE isoenzymes were identified: PDE I (Ca/calmodulin-stimulated), PDE II (cyclic guanosine monophosphate-stimulated), and PDE IV (cyclic adenosine monophosphate-specific). All PDE inhibitors relaxed the strips dose-dependently with an EC50 of 30 microM for papaverine, 40 microM for zaprinast, 25 microM for Quazinone, and 0.1 microM for rolipram. The existence of three different PDE isoenzymes was shown in this study. The ureter-relaxing effect of the PDE IV inhibitor at low concentrations, combined with its low effect on the systemic circulatory parameters, may open a possibility of using selective PDE IV inhibitors in the treatment of ureteral colics or ureteral stones.
Phosphodiesterase 4-dependent regulation of cyclic AMP levels and leukotriene B4 biosynthesis in human polymorphonuclear leukocytes
Eur J Pharmacol 1999 Feb 19;367(2-3):343-50.PMID:10079010DOI:10.1016/s0014-2999(98)00987-x.
Several selective phosphodiesterase 4 inhibitors were found to be potent inhibitors of the N-formyl-Met-Leu-Phe (fMLP)-induced leukotriene B4 biosynthesis by human polymorphonuclear leukocytes with IC50s in the nanomolar range (0.09-26 nM). The rank order of potency was 6-(4-pyridylmethyl)-8-(3-nitrophenyl)quinoline (RS-14203) > 3-benzyl-5-phenyl-3H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-one (KF18280) > 8-aza-1-(3-nitrophenyl)-3-(4-pyridylmethyl)-2,4-quinazoline dione (RS-25344) > 3-cyclo-pentyloxy-N-[3,5-dichloro-4-pyridyl]-4-methoxybenzamide (RP-73401) > R-rolipram > R-4-[2-(3-cyclopentyloxy-4-methoxyphenyl)-2-phenylethyl] pyridine (CDP840)> S-rolipram. Isoproterenol (IC50 = 350 nM) and prostaglandin E2 (IC50 = 59 nM) also suppressed leukotriene B4 biosynthesis. Inhibitors of the phosphodiesterase 1 (8-methoxymethyl-1-methyl-3-(2-methylpropyl)xanthine (8-MeOMe-IBMX)), phosphodiesterase 2 (erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA)), phosphodiesterase 3 (Quazinone and milrinone) and phosphodiesterase 5 (zaprinast and dipyridamole) had no inhibitory effects on the fMLP-induced leukotriene B4 biosynthesis (IC50s > 20 microM). All phosphodiesterase 4 inhibitors caused an accumulation of cellular cyclic AMP to 140-185% over the basal level of fMLP-treated control cells, comparable to that observed with high concentrations of isoproterenol and prostaglandin E2. In contrast, the complete inhibition of leukotriene B4 production by 5-lipoxygenase and 5-lipoxygenase-activating protein (FLAP) inhibitors had no effect on cyclic AMP levels. Phosphodiesterase 1, 2, 3 and 5 inhibitors had little effect on the level of cellular cyclic AMP (89-126% of the basal cyclic AMP level). Dose-dependencies for R-rolipram, RS-14203 and CDP840 indicated that the maximal accumulation of cyclic AMP occurred at concentrations of phosphodiesterase 4 inhibitors higher than those required for the inhibition of leukotriene B4 production. The presence of a mixture of 8-MeOMe-IBMX, EHNA, milrinone and zaprinast to inhibit phosphodiesterase 1, 2, 3 and 5 had little effect on the dose-dependence of R-rolipram for the inhibition of leukotriene B4 biosynthesis or cyclic AMP accumulation. These data demonstrate that selective phosphodiesterase 4 inhibitors can inhibit the fMLP-induced leukotriene B4 biosynthesis in human polymorphonuclear leukocytes with a potency similar or greater than that of potent 5-lipoxygenase or FLAP inhibitors. This inhibition is accompanied by small variations in the levels of cellular cyclic AMP and appears to proceed independently of the other phosphodiesterases.
Mechanism of SNAP potentiating antiproliferative effect of calcitonin gene-related peptide in cultured vascular smooth muscle cells
J Mol Cell Cardiol 1999 Sep;31(9):1599-606.PMID:10471344DOI:10.1006/jmcc.1999.0991.
We previously showed that CGRP inhibits cell proliferation which correlates with an elevation of cAMP levels in rabbit aortic vascular smooth muscle cells (VSMCs). The present study determined the effects of S-nitroso-N-acetylpenicillamine (SNAP, a nitric oxide donor) on CGRP-induced antiproliferative effects and cellular mechanism in cultured rabbit aortic VSMCs. The cells (in fifth-sixth passage) were exposed to 2.5% fetal bovine serum for 24 h in the presence or absence of SNAP, hCGRP or both.(3)H-thymidine incorporation was used to measure DNA synthesis. The results showed that SNAP (60-100 microm) significantly inhibited the proliferation and elevated cGMP levels in cultured rabbit aortic VSMCs. In combination, however, SNAP (30 microm) potentiated hCGRP (10-100 n m)-induced antiproliferation. SNAP (30 microm) and hCGRP (10-100 n m) or forskolin (10 microm), an activator of adenylate cyclase, caused more than additive cAMP elevations, but not cGMP elevations, in these cells. Quazinone, an inhibitor of cGMP-inhibited-phosphodiesterase (cGI-PDE, PDE3), or SNAP plus Quazinone caused a similar potentiation as SNAP of the hCGRP-induced elevations of cAMP levels. The data indicate that SNAP-induced potentiation of CGRP's effects likely involves inhibition of cGI-PDE, thus allowing enhanced accumulation of cAMP that mediates the antiproliferative effects of hCGRP in cultured rabbit aortic VSMCs.