Trapidil (AR-12008)
(Synonyms: 唑嘧胺; AR-12008) 目录号 : GC32458
An inhibitor of PDGF-induced activity and an antiplatelet agent
Cas No.:15421-84-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Trapidil is an inhibitor of PDGF-induced activity and an antiplatelet agent.1,2 It inhibits PDGF-induced proliferation of U251MG glioma cells and isolated rat aortic smooth muscle cells in a concentration-dependent manner. Trapidil (1 mM) inhibits platelet aggregation induced by ADP, arachidonic acid , or U-46619 in washed isolated human platelets.3 It reduces increases in intimal thickness and prevents restenosis induced by balloon angioplasty in rabbits fed a high-cholesterol diet when administered at a dose of 30 mg/kg.4
1.Kuratsu, J., and Ushio, Y.Antiproliferative effect of trapidil, a platelet-derived growth factor antagonist, on a glioma cell line in vitroJ. Neurosurg.73(3)436-440(1990) 2.Hoshiya, M., and Awazu, M.Trapidil inhibits platelet-derived growth factor-stimulated mitogen-activated protein kinase cascadeHypertension31(2)665-671(1998) 3.Mazurov, A.V., Yu, M., Leytin, V.L., et al.Decrease of platelet aggregation and spreading via inhibition of the cAMP phosphodiesterase by trapidilFEBS Lett.172(2)167-171(1984) 4.Liu, M.W., Roubin, G.S., Robinson, K.A., et al.Trapidil in preventing restenosis after balloon angioplasty in the atherosclerotic rabbitCirculation81(3)1089-1093(1990)
| Cas No. | 15421-84-8 | SDF | |
| 别名 | 唑嘧胺; AR-12008 | ||
| Canonical SMILES | CC1=NC2=NC=NN2C(N(CC)CC)=C1 | ||
| 分子式 | C10H15N5 | 分子量 | 205.26 |
| 溶解度 | Water : ≥ 105 mg/mL (511.55 mM) | 储存条件 | Store at -20°C, protect from light |
| 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 | 4.8719 mL | 24.3593 mL | 48.7187 mL |
| 5 mM | 0.9744 mL | 4.8719 mL | 9.7437 mL |
| 10 mM | 0.4872 mL | 2.4359 mL | 4.8719 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。
An Overview on Synthetic and Medicinal Perspectives of [1,2,4]Triazolo[1,5-a]pyrimidine Scaffold
Chem Biodivers 2022 Sep;19(9):e202200291.PMID:35946991DOI:10.1002/cbdv.202200291.
[1,2,4]Triazolo[1,5-a]pyrimidine is an important heterocyclic scaffold known to have a wide range of pharmacological activities such as anticancer, antimicrobial, anti-tubercular, CB2 cannabinoid agonists, feticide, and adenosine antagonists. Several clinical trials and marketed drugs such as Trapidil, Essramycin, Pyroxsulam, DSM-265, Flumetsulam, GNF-6702, and Cevipabulin indicate the potential of [1,2,4]triazolo[1,5-a]pyrimidine moiety with various functional groups in medicinal chemistry. Herein, we represent a concise report focusing on the synthetic strategies used for diversely substituted [1,2,4]triazolo[1,5-a]pyrimidine analogs and their pharmacological applications. To the best of our knowledge, since 1980, we are the first to write a review on this emerging scaffold, which reveals the synthetic strategies, and pharmacological activities of differently substituted [1,2,4]triazolo[1,5-a]pyrimidine with special emphasis on structure-activity relationship studies.
[Trapidil after one year]
Minerva Cardioangiol 1993 May;41(5):159-66.PMID:8373465doi
Present knowledge about cerebral limb ischemia has pointed out the importance of a versatile pharmacological approach, which considers not only the hydraulic aspect of the problem through a vasodilating action, but also all the hemorheologic and hemocoagulative implications, which seem to characterize the pathology itself. For about one year Trapidil has been entering the therapeutic treatments for arterio-vascular diseases in Italy; this drug was already known and tested abroad. Trapidil has shown a more complete antithrombocytic activity than other antiaggregating drugs; as a matter of fact it inhibits the formation of TXA2 through a mechanism of receptorial antagonism and at the same time it favours an increase of prostacyclina from the arterial walls. Moreover this drug is provided with a selective inhibition of the mitogenic effects of PDGF, which occurs for the block of the receptorial binding of this factor at the level of the myointimal cells. In conclusion, in some experimental models Trapidil seems to be able to improve the hemoreologic properties of the blood. Some different clinical studies have demonstrated the therapeutic effectiveness of Trapidil. In the treating of claudication and of the pain during the rest in AOCP, we want to report two studies which have shown a general improving either of the free interval of run or a reduction of the pain. In particular the polycentric study of Bonavita has examined 200 patients afflicted with AOCP at II and III stage, who were divided into three treatment groups: Trapidil, ticlopidina and picotamide.
Trapidil induces osteogenesis by upregulating the signaling of bone morphogenetic proteins
Cell Signal 2018 Sep;49:68-78.PMID:29879471DOI:10.1016/j.cellsig.2018.06.001.
Platelet-derived growth factor receptor (PDGFR) signaling has been shown to inhibit osteogenesis. However, therapeutic efficacy of inhibiting PDGF signaling to bone regeneration in vivo and the specific mechanisms by which PDGFR signaling inhibits osteogenic differentiation remain unclear. In the present study, we examined the osteogenic effect of inhibiting PDGFR using Trapidil, a PDGFR antagonist, in vivo and in vitro, and evaluated its mechanisms. A rat calvarial defect model was analyzed by micro-computed tomography and histology to determine the pro-osteogenic effect of Trapidil in vivo. In addition, primary mouse calvarial osteoblast precursors were cultured in osteogenic differentiation medium with Trapidil to study the mechanisms. Trapidil greatly promoted bone regeneration in a rat calvarial defect model and osteogenic differentiation of calvarial osteoblast precursors. For the mechanisms, Trapidil induced phosphorylation of Smad1/5/9 and mitogen-activated protein kinase (MAPK) leading to enhance expression of Runx2, crucial transcription factor for osteogenesis. The pro-osteogenic effects of Trapidil were inhibited by LDN193189, specific inhibitor of bone morphogenetic protein (BMP) receptor, ALK2 and ALK3, and by depletion of ALK3, and treatment with noggin, an antagonist of BMPs. Moreover, Trapidil showed a synergistic effect with BMP2 on osteogenic differentiation. In conclusion, Trapidil induced BMPR activity through upregulation of BMP signaling, leading to promoted osteogenesis in vitro and in vivo. Attenuated BMPR activity may be involved in the inhibition of osteogenesis by PDGFR signaling.
Trapidil, a platelet-derived growth factor antagonist, inhibits osteoclastogenesis by down-regulating NFATc1 and suppresses bone loss in mice
Biochem Pharmacol 2013 Sep 15;86(6):782-90.PMID:23928189DOI:10.1016/j.bcp.2013.07.015.
Trapidil, a platelet-derived growth factor antagonist, was originally developed as a vasodilator and anti-platelet agent and has been used to treat patients with ischemic coronary heart, liver, and kidney disease. In this study, we investigated the effects of Trapidil on osteoclastogenesis and elucidated the possible mechanism of action of Trapidil. Trapidil strongly inhibited osteoclast formation in co-cultures of bone marrow cells and osteoblasts without affecting receptor activator of NF-魏B ligand (RANKL) or osteoprotegerin expression in osteoblasts. In addition, Trapidil suppressed RANKL-induced osteoclast formation from osteoclast precursors. Trapidil reduced RANKL-induced expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), a master transcription factor for osteoclastogenesis, without affecting the expression of c-Fos that functions as a key upstream activator of NFATc1 during osteoclastogenesis. Ectopic expression of a constitutively active form of NFATc1 reversed the anti-osteoclastogenic effect of Trapidil, indicating that NFATc1 is a critical target of the anti-osteoclastogenic action of Trapidil. RANKL-induced calcium oscillation and Pim-1 expression, which are required for NFATc1 induction and osteoclastogenesis, were abrogated by Trapidil. Consistent with the in vitro results, Trapidil had a potent inhibitory effect on osteoclast formation and bone resorption induced by interleukin-1 in an animal model. Taken together, our data demonstrate that Trapidil abrogates RANKL-induced calcium oscillation and Pim-1 expression required for NFATc1 induction, thereby inhibiting osteoclastogenesis.
Mechanism of cardiovascular action of Trapidil
Arzneimittelforschung 1980;30(8):1264-8.PMID:6254546doi
In anaesthetized, open-chest dogs N,N-diethyl-5-methyl[1,2,4]triazolo[1,5-alpha]pyrimidine-7-amine (Trapidil) in doses of 0.3--3 mg/kg i.v. produced increases in coronary sinus outflow and heart rate and decreases in systemic blood pressure and coronary resistance in a dose-dependent manner. Trapidil produced an increase in myocardial oxygen consumption but virtually no change in coronary arteriovenous oxygen difference. At 1.8 mg/kg i.v. of the drug coronary resistance fell to half of the pre-drug value and coronary sinus outflow almost doubled, and so did myocardial oxygen consumption. In isolated, blood-perfused dog heart preparations, Trapidil produced coronary vasodilator and positive inotropic and chronotropic effects. Theophylline produced similar effects. Trapidil was a more positive inotropic than positive chronotropic agent, and so was theophylline but to a lesser degree than Trapidil. In producing vasodilator and positive inotropic effects Trapidil was about 3 times more effective than theophylline. Trapidil and theophylline inhibited the cyclic AMP phosphodiesterase (PDE) activity in crude extracts prepared from the dog ventricular muscle. In this respect Trapidil was nearly 3 times more potent than theophylline. It is suggested that PDE inhibition would be a fundamental mechanism of action of Trapidil.