Trombodipine (PCA-4230)
(Synonyms: PCA-4230) 目录号 : GC32610
曲波地平 (PCA-4230) 是一种抗血栓剂。
Cas No.:113658-85-8
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
Cell experiment: | To estimate the proportions of cells in different phases of the cell cycle, cellular DNA contents are measured by flow cytometry. Cells are plated, allowed to attach overnight, and placed in serum-free medium for 48 h. Trombodipine (50 μM) is added at selected points during serum repletion. At the specified times after serum addition, the cells are harvested by trypsinization, washed with PBS, pelleted and resuspended in PBS containing 0.6% Nonidet P-40 and 100 μg/mL propidium iodide (PI). Flow cytometric analyses are done with a FACScan flow cytometer[1]. |
References: [1]. del Rio M, et al. Antiproliferative effects of PCA-4230, a new antithrombotic drug, in vascular smooth muscle cells. Br J Pharmacol. 1997 Apr;120(7):1360-6. | |
Trombodipine is an antithrombotic agent.
Trombodipine is an antithrombotic agent. Exposure to 50 μM Trombodipine reveals an important stasis of growth. The percentage of inhibition exerted by 1 μM Trombodipine on day 3, 5 and 7 of the growth curve is 22.0±4.5, 32.0±3.0 and 29.4±6.0%, respectively (P<0.05). The inhibitory effect of Trombodipine on cell proliferation is reversible and after removal of Trombodipine the proliferation of the cells is resumed[1]. Addition of Trombodipine reduces cell number in a dose-dependent manner over a period of 4 to 6 days in culture. When compare to control cultures at the latest time points investigated, 5 μM Trombodipine decreases the number of E19P cells and human VSMCs by 25 and 21%, respectively, whereas 50 μM Trombodipine reduces E19P and human VSMC number by 85 and 74%, respectively[2].
[1]. del Rio M, et al. Antiproliferative effects of PCA-4230, a new antithrombotic drug, in vascular smooth muscle cells. Br J Pharmacol. 1997 Apr;120(7):1360-6.
| Cas No. | 113658-85-8 | SDF | |
| 别名 | PCA-4230 | ||
| Canonical SMILES | O=C(C1=C(C)NC(C)=C(C(OCC)=O)C1C)OCCN(C(C2=C3C=CC=C2)=O)S3(=O)=O | ||
| 分子式 | C21H24N2O7S | 分子量 | 448.49 |
| 溶解度 | Soluble in DMSO | 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 | 2.2297 mL | 11.1485 mL | 22.297 mL |
| 5 mM | 0.4459 mL | 2.2297 mL | 4.4594 mL |
| 10 mM | 0.223 mL | 1.1149 mL | 2.2297 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。
Antiproliferative effects of PCA-4230, a new antithrombotic drug, in vascular smooth muscle cells
Br J Pharmacol 1997 Apr;120(7):1360-6.PMID:9105713DOI:10.1038/sj.bjp.0701035.
1. In the present study we examined the effects of PCA-4230, a novel antithrombotic agent, on the growth of cultured A10 vascular smooth muscle cells (rat'aorta). 2. The action of PCA-4230 on cell proliferation and on serum-induced DNA synthesis was determined by measuring the cell number and the incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU), respectively. 3. PCA-4230 reversibly inhibited vascular smooth muscle cell proliferation. The increase in cell number was significantly reduced in the presence of 1 and 50 microM PCA-4230. 4. DNA synthesis was concentration-dependently inhibited by PCA-4230 (0.5 to 50 microM) in A10 cells that were synchronized by 48 h serum starvation and then re-stimulated by serum repletion, with an IC50 value of 13 microM. However, serum-induced DNA synthesis in bovine aortic endothelial cells was not significantly affected by PCA-4230. In addition, PCA-4230 (50 microM) caused a significant drop in PDGF-BB-mediated BrdU incorporation in A10 cells. 5. The effect of PCA-4230 on serum-induced DNA synthesis was compared to that elicited by nifedipine, another dihydropyridine-class inhibitor of vascular smooth muscle proliferation. PCA-4230 (10 microM) elicited a degree of inhibition similar to that of nifedipine at equimolar concentration. 6. To define the nature of the cell proliferation inhibition, an evaluation of cell cycle progression was undertaken. Flow cytometry studies of DNA content in synchronized cells revealed a block of the serum-inducible cell cycle progression. This inhibitory effect was markedly reduced when PCA-4230 was added 2 h after serum repletion. 7. Accordingly, PCA-4230 (50 microM) caused a 95 and 90% decrease in the elevation of c-fos and c-jun proto-oncogenes expression as evaluated by Northern blot analysis of mRNA induced early after serum addition. 8. The present results indicate that PCA-4230 inhibits vascular smooth muscle cell proliferation, in culture, by altering the cell cycle progression. Flow cytometric studies of DNA content and the down regulation of c-fos and c-jun proto-oncogenes, suggest that the drug is acting at the early G0/G1 transition phase. PCA-4230 may hold promising potential for the prevention of structural abnormalities of blood vessels associated with atherosclerosis and vascular diseases.
Interaction of platelets with subendothelium in rats treated with PCA-4230, a new antithrombotic agent. Effect of PCA-4230 on experimental thrombosis
Haemostasis 1992;22(4):202-10.PMID:1468723DOI:10.1159/000216320.
The effects of a new antithrombotic compound, PCA-4230, versus ticlopidine were investigated using an experimental thrombosis and vascular endothelial injury model in rats. Both PCA-4230 and ticlopidine protected rat arteries from the formation of prominent thrombi and most of microthrombi without modifying the formation of a first platelet monolayer. Neither coagulation parameters nor fibrinolysis were modified by these antithrombotic drugs. Neither PCA-4230 nor ticlopidine affected thromboxane A2 production in rats, whereas unlike PCA-4230, ticlopidine inhibited ex vivo fibrinogen binding to the fibrinogen receptor found on the platelet membrane. In conclusion, PCA-4230 and ticlopidine inhibited thrombus formation in vivo by a platelet-dependent mechanism which may be different for one or the other drug in spite of the fact that the protective effect measured in this thrombosis model is quite similar for either PCA-4230 or ticlopidine. The above-mentioned results clearly show that PCA-4230 is a new potent agent with both antivascular-damaging and antiplatelet activities, and devoid of effects on coagulation and fibrinolytic systems.
Inhibition of the cyclin D1/E2F pathway by PCA-4230, a potent repressor of cellular proliferation
Br J Pharmacol 2001 Apr;132(7):1597-605.PMID:11264255DOI:10.1038/sj.bjp.0703945.
1. Tight control of cellular growth is essential to ensure normal tissue patterning and prevent pathological responses. Excessive vascular smooth muscle cell (VSMC) proliferation is associated with the pathophysiology of atherosclerosis and restenosis post-angioplasty. Thus, drug targeting of pathological VSMC growth may be a suitable therapeutic intervention in vascular proliferative diseases. 2. In the present study, we investigated the mechanisms underlying VSMC growth arrest induced by the pharmacological agent PCA-4230. Addition of PCA-4230 to cultured VSMCs blocked the induction of cyclin D1 and cyclin A expression normally seen in serum-restimulated cells. Moreover, PCA-4230 inhibited cyclin-dependent kinase 2 (CDK2) activity and abrogated hyperphosphorylation of the retinoblastoma (Rb) gene product. Similarly, PCA-4230-dependent growth arrest of transformed cell lines correlated with reduced level of cyclin D1 protein and inhibition of CDK2 activity. Consistent with these findings, PCA-4230 repressed serum-inducible cyclin A promoter activity, and overexpression of either cyclin D1 or E2F1 efficiently circumvented this inhibitory effect. Importantly, adenovirus-mediated overexpression of E2F1 restored S-phase entry in PCA-4230-treated VSMCs, demonstrating that PCA-4230 represses cyclin A gene expression and VSMC growth via inhibition of the cyclin D1/E2F pathway. 3. Because of its ability to inhibit the growth of human VSMCs and transformed cell lines, future studies are warranted to assess whether PCA-4230 may be a suitable therapeutic intervention for the treatment of hyperproliferative disorders, including cardiovascular disease and cancer.
Involvement of cyclic GMP in the mode of action of a new antithrombotic agent PCA-4230; inhibition of the platelet cyclic GMP dependent phosphodiesterase
Thromb Res 1997 Sep 15;87(6):547-57.PMID:9330437DOI:10.1016/s0049-3848(97)00184-9.
The effect of PCA-4230, a new dihydropyridine derivative with a potent antithrombotic activity, on cyclic nucleotide phosphodiesterase in platelets was studied. PCA-4230 inhibited (54%) cyclic GMP hydrolytic activity of a platelet cytosolic fraction, whereas it did not affect that of cyclic AMP. Results suggested that PCA-4230 inhibited a cyclic GMP-dependent phosphodiesterase, known as cGB PDE or type V, on a purified enzyme from rabbit platelets by a non-competitive-uncompetitive type inhibition. In addition, PCA-4230 potentiated the increase in both cyclic GMP and cyclic AMP levels evoked by sodium nitroprusside. Furthermore, PCA-4230 and forskolin caused a synergistic effect in cyclic AMP, and also potentiated the phosphorylation of 50 kDa and 22 kDa proteins, reported as substrates of cyclic GMP- and cyclic AMP-dependent protein kinases that are related to the inhibition of platelet functions. Finally, PCA-4230 also potentiated the forskolin- and sodium nitroprusside-inhibited serotonin release evoked by thrombin, probably related to the increased cyclic nucleotide level.
Dissociation between secretion and protein phosphorylation in agonist-stimulated platelets; action of PCA-4230, a new antithrombotic drug
Thromb Res 1994 Jul 15;75(2):121-32.PMID:7974386DOI:10.1016/0049-3848(94)90061-2.
We have studied the effects of PCA-4230, a new dihydropyridine derivative with antithrombotic activity, on the secretion of dense and alpha-granules from platelets and on the protein phosphorylation in platelets after stimulation by agonists. The drug prevented both dense and alpha-granule secretion evoked by thrombin, platelet-activating factor (PAF) and ionophore A23187, the former secretion being more sensitive than the latter one to the PCA-4230 action. These inhibitory effects on secretion processes did not correlate with the differential action of PCA-4230 on protein phosphorylation. Thus, the 40 kDa protein phosphorylation evoked by thrombin was potentiated whereas that elicited by ionophore A23187 was partially inhibited. The 20 kDa protein phosphorylation was practically insensitive to the drug action. These data, together with previous evidence reported by us on PCA-4230, lead us to suggest the existence of a common and critical step for platelet secretion evoked by agonists with different signal transduction pathways.