Cicaprost
(Synonyms: ZK 96480) 目录号 : GC41222Stable analog of prostacyclin
Cas No.:94079-80-8
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Prostaglandin I2 (PGI2, prostacyclin) is the most potent endogenous vasodilator that affects both the systemic and pulmonary circulation.[1] Cicaprost is a PGI2 analog that is orally active with prolonged availability in vivo, having a terminal half life in plasma of one hour.[2][3] In addition to their effects on smooth muscle, PGI2 analogs, including cicaprost, have been shown to inhibit the pro-inflammatory actions of certain leukocytes, suppress cardiac fibrosis, and block mitogenesis of certain cell types.[4][5][6] Importantly, cicaprost has been shown to strongly reduce lung and lymph node metastasis in rats, suggesting that it might be useful in cancer therapy.[7]
Reference:
[1]. Moncada, S. Biology and therapeutic potential of prostacyclin. Stroke 14(2), 157-168 (1983).
[2]. Kiriyama, M., Ushikubi, F., Kobayashi, T., et al. Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Br. J. Pharmacol. 122(2), 217-224 (1997).
[3]. Hildebrand, M., Staks, T., and Nieuweboer, B. Pharmacokinetics and pharmacodynamics of cicaprost in healthy volunteers after oral administration of 5 to 20 micrograms. European Journal of Clinical Pharmacology 39(2), 149-153 (1990).
[4]. Zhou, W., Hashimoto, K., Goleniewska, K., et al. Prostaglandin I2 analogs inhibit proinflammatory cytokine production and T cell stimulatory function of dendritic cells. Journal of Immunology 178, 702-710 (2007).
[5]. Chan, E.C., Dusting, G.J., Guo, N., et al. Prostacyclin receptor suppresses cardiac fibrosis: Role of CREB phosphorylation. Journal of Molecular and Cellular Cardiology 49, 176-185 (2010).
[6]. Castagnino, P., Kothapalli, D., Hawthorne, E.A., et al. Cell-type- and cell-cycle-specific anti-mitogenesis by cicaprost. Prostaglandins & Other Lipid Mediators 93, 20-24 (2010).
[7]. Schirner, M., Kraus, C., Lichtner, R.B., et al. Tumor metastasis inhibition with the prostacyclin analogue cicaprost depends on discontinuous plasma peak levels. Prostaglandins, Leukotrienes and Essential Fatty Acids 58(40, 311-317 (1998).
| Cas No. | 94079-80-8 | SDF | |
| 别名 | ZK 96480 | ||
| 化学名 | 2-[2-[(2E,3aS,4S,5R,6aS)-hexahydro-5-hydroxy-4-[(3S,4S)-3-hydroxy-4-methyl-1,6-nonadiyn-1-yl]-2(1H)-pentalenylidene]ethoxy]-acetic acid | ||
| Canonical SMILES | O[C@@H]1C[C@H](C/2)[C@H](CC2=C\COCC(O)=O)[C@H]1C#C[C@@H](O)[C@@H](C)CC#CCC | ||
| 分子式 | C22H30O5 | 分子量 | 374.5 |
| 溶解度 | 25mg/mL in DMSO, 30mg/mL in ethanol or DMF | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.6702 mL | 13.3511 mL | 26.7023 mL |
| 5 mM | 0.534 mL | 2.6702 mL | 5.3405 mL |
| 10 mM | 0.267 mL | 1.3351 mL | 2.6702 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。
Antimetastatic action of the prostacyclin analogue Cicaprost in experimental mammary tumors
Breast Cancer Res Treat 1996;38(1):133-41.PMID:8825130DOI:10.1007/BF01803791.
In breast cancer, the survival rate strongly depends on the number of lymph nodes involved. A drug with a specific inhibitory activity on lymph node and organ metastases would therefore be a candidate for adjuvant therapy after surgery. Prostacyclin and its stable analogues have been shown to interfere with certain steps of the metastatic cascade and to inhibit the number of lung colonies after i.v.-inoculation of various tumor cell lines. Our data reveal that Cicaprost, a metabolically stable and orally active analogue of prostacyclin, has pronounced antimetastatic effects in a series of spontaneously metastasizing rodent tumors. In the SMT 2a and 13762 MTLn3 mammary carcinomas of the rat, Cicaprost given daily from the day of tumor implantation strongly inhibits the number of lung metastases as well as lymph node weights without exerting an effect on the primary tumor. Even starting treatment when palpable primary tumors are present gives a pronounced antimetastatic activity. To demonstrate that Cicaprost has an effect on metastases already settled in the respective organ, treatment was started after surgical removal of the primary tumor. In the SMT 2a tumor, a strong inhibition of the number of metastases was shown. Interestingly, a perioperative treatment schedule was also effective in both models used. As primary tumor growth in vivo or proliferation in vitro remained unchanged by Cicaprost, its mode of action seems to be related to one or more mechanisms of the metastatic process. In tumor cell lines expressing a functional prostacyclin receptor, stimulated tumor cell migration is inhibited and changes of differentiation status are obvious. In conclusion, Cicaprost strongly inhibits lymph node and organ metastases of spontaneously metastasizing rodent mammary tumors with a mode of action different from cytostatic or antihormonal drugs.
Mechanism of cicaprost-induced desensitization in rat pulmonary artery smooth muscle cells involves a PKA-mediated inhibition of adenylyl cyclase
Am J Physiol Lung Cell Mol Physiol 2004 Aug;287(2):L352-9.PMID:15107293DOI:10.1152/ajplung.00270.2003.
Long-term infusion of prostacyclin, or its analogs, is an effective treatment for severe pulmonary arterial hypertension. However, dose escalation is often required to maintain efficacy. The aim of this study was to investigate the mechanisms of prostacyclin receptor desensitization using the prostacyclin analog Cicaprost in rat pulmonary artery smooth muscle cells (PASMCs). Desensitization of the cAMP response occurred in 63 nM Cicaprost after a 6-h preincubation with agonist. This desensitization was reversed 12 h after agonist removal, and resensitization was inhibited by 10 microg/ml of cycloheximide. Desensitization was heterologous since desensitization to other G(s)alpha-adenylyl cyclase (AC)-coupled agonists, isoproterenol (1 microM), adrenomedullin (100 nM), or bradykinin (1 microM), was also reduced by preincubation with Cicaprost. The reduced cAMP response to prolonged Cicaprost exposure appeared to be due to inhibition of AC activity since the responses to the directly acting AC agonist forskolin (3 microM) and the selective AC5 activator NKH-477 were similarly reduced. Expression of AC2 and AC5/6 protein levels transiently decreased after 1 h of Cicaprost exposure. The PKA inhibitor H-89 (1 microM) added 1 h before Cicaprost preincubation (6 h, 63 nM) completely reversed cicaprost-induced desensitization, whereas the PKC inhibitor bisindolylmaleimide (100 nM) was only partly effective. Desensitization was not prevented by the G(i) inhibitor pertussis toxin. In conclusion, chronic treatment of PASMCs with Cicaprost induced heterologous, reversible desensitization by inhibition of AC activity. Our data suggest that heterologous G(s)alpha desensitization by Cicaprost is mediated predominantly by a PKA-inhibitable isoform of AC, most likely AC5/6.
Cell-type- and cell-cycle-specific anti-mitogenesis by Cicaprost
Prostaglandins Other Lipid Mediat 2010 Sep;93(1-2):20-4.PMID:20457271DOI:10.1016/j.prostaglandins.2010.04.004.
Stents eluting anti-proliferative drugs limit restenosis, but drugs commonly used to date are relatively non-specific cytostatic agents which inhibit proliferation of intimal endothelial cells as well as medial smooth muscle cells and may thereby contribute to the clinical complications associated with angioplasty. In an effort to identify a more specific anti-proliferative agent, we compared the effects of rapamycin to those of Cicaprost, a mimetic of the naturally occurring anti-mitogen, PGI(2). Rapamycin and Cicaprost were both strongly anti-mitogenic in vascular smooth muscle cells (VSMCs). But unlike rapamycin, Cicaprost did not inhibit mitogenesis in aortic endothelial cells even when used at concentrations >10-fold higher than its ED(50) for VSMCs. Similarly, both rapamycin and Cicaprost have been reported to regulate levels of the cdk inhibitor, p27(kip1). But rapamycin remained anti-mitogenic in p27(kip1)-null VSMCs whereas the anti-mitogenic effect of Cicaprost was completely dependent on p27(kip1). We conclude that stable PGI(2) mimetics may be highly specific inhibitors of p27(kip1)-dependent VSMC proliferation after vascular injury.
Pharmacokinetics of 3H-cicaprost in healthy volunteers
Prostaglandins 1989 Feb;37(2):259-73.PMID:2657866DOI:10.1016/0090-6980(89)90062-2.
Cicaprost (5-[(E)-(1S,5S,6S,7R)-7-hydroxy-6-[(3S,4S)-3-hydroxy-4-methylnona- 1,6- diinyl]-bicyclo[3.3.0]octan-3-yliden]-3-oxapentanoic acid, ZK 96 480) is a novel PGI2-derivative, which is chemically stable and not subject to metabolic degradation in rats and cynomolgus monkeys. The pharmacokinetics of Cicaprost were studied in six healthy volunteers (age: 54-74 y) after i.v. infusion (2.1 micrograms over 60 min) and p.o. dosage (7.6 micrograms) of the tritiated compound. All treatments were well-tolerated by the test subjects. At the end of the infusion plasma levels of approximately 100 pg/ml were reached, declining biphasically with half-lives of 3-4 min and 64 +/- 21 min. Total clearance was 3.8 +/- 0.5 ml/min/kg. The oral dosage resulted in peak plasma levels of 251 +/- 90 pg/ml occurring at 23 +/- 5 min post dose. The terminal half-life in the plasma was 115 +/- 30 min. Gastro-intestinal absorption and absolute bioavailability of Cicaprost was complete. After both routes of administration approx. 60% of dose was excreted with the urine within 24 h, whereas fecal 3H-excretion lasted for several days and accounted for approx. 35%. Radiochromatography revealed that Cicaprost was metabolically stable in plasma and urine. In the feces several degradation products were observed apart from approx. 30% of the dose fraction being excreted unchanged by that route. The present results demonstrate that Cicaprost is an orally completely bioavailable, metabolically stable PGI2-mimetic which may be an ideal candidate for oral therapy because of its pharmacokinetic characteristics.
Development and validation of a sensitive and specific radioimmunoassay for the determination of Cicaprost in biological samples
J Immunoassay 1994 May;15(2):171-90.PMID:8040351DOI:10.1080/15321819408013946.
Cicaprost is a potent, chemically and metabolically stable PGI2-mimetic. Pharmacodynamic effects were observed after oral administration of approximately 10 micrograms in man when plasma levels were in the low pg-range. The present report describes the development of a selective antiserum and a tracer with high specific activity and their use for the RIA determination of Cicaprost in biological samples. Cicaprost-[3H]-methylester with a specific activity of 819 GBq/mmol was used as a tracer. RIA-analyses were carried out with 0.05-0.5 ml plasma adjusted to pH 2 with 1 N HCl and extracted with 2.5 ml diethylether. Separation of antiserum bound and unbound Cicaprost was achieved by the charcoal method. Extraction recovery of Cicaprost was approximately 90% at pH approximately 2. The detection limit of the assay was 10-20 pg/ml plasma. Coefficients of variations were 6, 3 and 9% (within-day, n = 5) and 25, 12 and 10% (day-to-day, n = 11) at 50, 100 and 200 pg/ml. HPLC-chromatograms of plasma extracts did not reveal any peak apart from Cicaprost, demonstrating the specificity of the method. The present RIA for Cicaprost exhibits high specificity and sensitivity and will be used for further bioanalyses in pharmacokinetic study.