Pinane Thromboxane A2
(Synonyms: 15(S)-Pinane Thromboxane A2, Pinane TXA2, PTA2) 目录号 : GC41174A TP receptor antagonist and inhibitor of TX synthase
Cas No.:71111-01-8
Sample solution is provided at 25 µL, 10mM.
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- Purity: >98.00%
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Pinane thromboxane A2 (PTA2) is a stable analog of TXA2. It is a TP receptor antagonist and an inhibitor of thromboxane synthase. PTA2 inhibits U-46619-induced cat coronary artery constriction (ID50 = 0.1 µM), U-46619-induced aggregation of human platelets (IC50 = 2 µM), and rabbit platelet thromboxane synthase (ID50 = 50 µM). PTA2 does not affect PGI synthase up to a concentration of 100 µM.
| Cas No. | 71111-01-8 | SDF | |
| 别名 | 15(S)-Pinane Thromboxane A2, Pinane TXA2, PTA2 | ||
| Canonical SMILES | CCCCC[C@H](O)/C=C/[C@H]1C[C@H]2C[C@H](C2(C)C)[C@@H]1C/C=C\CCCC(O)=O | ||
| 分子式 | C24H40O3 | 分子量 | 376.6 |
| 溶解度 | DMF: >50 mg/ml,DMSO: >25 mg/ml,Ethanol: >100 mg/ml,PBS pH 7.2: >100 µ g/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。 | ||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6553 mL | 13.2767 mL | 26.5534 mL |
| 5 mM | 0.5311 mL | 2.6553 mL | 5.3107 mL |
| 10 mM | 0.2655 mL | 1.3277 mL | 2.6553 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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。
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Pinane Thromboxane A2 analogues are non-selective prostanoid antagonists in rat and human stomach muscle
Br J Pharmacol 1982 Dec;77(4):591-6.PMID:6758907DOI:10.1111/j.1476-5381.1982.tb09336.x.
1 Pinane Thromboxane A2 (PTxA2) and its epi-OH isomer were studied on rat and human stomach longitudinal muscle. 2 PTxA2 (0.5 micrograms/ml) usually caused a slight contraction of rat gastric fundus. Contractions to PGE2, PGF2 alpha, PGI2 and epoxymethano analogues of PGH2 (U-46619 and U-44069) were substantially inhibited, whereas those to PGD2 and acetylcholine were only slightly reduced. 3 In human stomach, PTxA2 0.5 micrograms/ml rarely stimulated the muscle. Contractions to PGE2, PGF2 alpha and U-46619 were antagonized, with little effect on those to acetylcholine. 4 epi-PTxA2 (0.5 micrograms/ml) did not affect rat gastric tone. It was moderately potent against PGI2 on rat gastric fundus, but was less effective than PTxA2 against U-44069.
Preservation of ischemic myocardium by Pinane Thromboxane A2
Am J Physiol 1980 Jan;238(1):H87-92.PMID:7356037DOI:10.1152/ajpheart.1980.238.1.H87.
Pinane Thromboxane A2 (PTA2), a thromboxane A2 analog has been shown to antagonize the vasoconstriction and platelet aggregation induced by thromboxane A2, in addition to specifically inhibiting thromboxane synthetase. Because thromboxane A2 generation would be detrimental in acute myocardial ischemia (MI) by both decreasing coronary blood flow and increasing platelet aggregation, inhibition of thromboxane production and action may be beneficial in myocardial ischemia. In pentobarbital-anesthetized cats, the left anterior descending coronary artery was ligated, and PTA2 (0.5 mumol . kg-1 . h-1) or a Na2CO3 vehicle was infused 30 min post-MI for 270 min. Compared to vehicle-treated MI cats, PTA2 prevented the increase in plasma thromboxane levels seen at 2 through 5 h (P less than 0.005 at 2 through 5 h) and prevented the large increase in plasma CK activities at 4 and 5 h (P less than 0.025). In addition, PTA2 treatment abolished the differences in myocardial CK activities between ischemic and nonischemic regions and prevented the decrease in percent-bound cathepsin D in the ischemic region. Moreover, ECG analysis revealed a decreased incidence of premature beats in PTA2-treated MI cats as compared to MI-vehicle cats. In summary, these data indicate that PTA2 protects the ischemic myocardium and provide further evidence that inhibition of thromboxane formation, in addition to antagonism of its activity, is beneficial during the early stages of acute myocardial ischemia.
Anti-thromboxane A2 actions of Pinane Thromboxane A2 derivatives
Prostaglandins Leukot Med 1982 Nov;9(5):503-9.PMID:6960376DOI:10.1016/0262-1746(82)90031-2.
Six pinane-thromboxane A2 analogs have been synthesized and tested for their ability to antagonize carbocyclic thromboxane A2 (CTA2) induced coronary vasoconstriction and prostaglandin endoperoxide analog induced platelet aggregation. Two of the derivatives, 5C-15S BPTA2 and 5T-15S BPTA2 and 5T-15S BPTA2 (1 microM) showed 76 +/- 3 and 72 +/- 9 percent inhibition of CTA2 (15 nM) induced vasoconstriction of cat coronary arteries respectively, while the other compounds showed between 15 and 50 percent inhibition at 1.0 and 2.0 microM. 5C-15S BPTA2 also antagonized prostaglandin-endoperoxide analog induced human platelet aggregation, although the other compounds showed little or no antagonism of aggregation in this system.
Thromboxane A2 analogues inhibit the metabolism of thromboxane B2 in perfused guinea-pig lung
Biochim Biophys Acta 1983 Nov 29;754(2):190-200.PMID:6652102DOI:10.1016/0005-2760(83)90161-3.
The effect of four thromboxane A2-like analogues as inhibitors of thromboxane B2 uptake and metabolism to 13,14-dihydro-15-keto-thromboxane B2 was studied in the perfused guinea-pig lung. We used 5-min infusions containing 1 muCi [3H]thromboxane B2 (10 ng/ml) and measured uptake/accumulation (as tissue to medium ratio) and metabolism to 13,14-dihydro-15-ketothromboxane B2 by radio-TLC. The results showed that thromboxane B2 metabolism is saturable and exhibits substantial dose-dependent inhibition of both processes by U46619 and U44069 endoperoxide analogues (50% inhibition, ID50, in the range 0.5-0.9 microM), Pinane Thromboxane A2 (a thromboxane A2 partial agonist, ID50 against metabolism, 0.7 microM) and the thromboxane A2 mimetic EPO11 (ID50 against metabolism, 2.6 microM). These agents affected uptake and enzyme transformation steps differentially, thus strengthening the evidence that thromboxane B2 metabolism is a multi-step, uptake-dependent process in this tissue. U46619 did not affect prostaglandin F2 alpha metabolism, nor did prostaglandin F2 alpha inhibit thromboxane B2 metabolism, confirming that thromboxane B2 uptake/metabolism is distinct from the process which handles prostaglandins. Of the four analogues, only pinane thromboxane was a significant substrate for 15-hydroxyprostaglandin dehydrogenase and it was also the best inhibitor of 15-hydroxyprostaglandin dehydrogenase in purified enzyme preparations. These results advance our understanding of the inactivation in lung of thromboxane B2 and invite study of thromboxane A2 itself.
The G12 family of G proteins as a reporter of thromboxane A2 receptor activity
Mol Pharmacol 2006 Apr;69(4):1433-40.PMID:16418336DOI:10.1124/mol.105.019703.
Despite advances in the understanding of pathways regulated by the G12 family of heterotrimeric G proteins, much regarding the engagement of this family by receptors remains unclear. We explore here, using the thromboxane A2 receptor TPalpha, the ability of G12 and G13 to report differences in the potency and efficacy of receptor ligands. We were interested especially in the potential of the isoprostane 8-iso-prostaglandin F (8-iso-PGF2alpha), among other ligands examined, to activate G12 and G13 through TPalpha explicitly. We were also interested in the functionality of TPalpha-Galpha fusion proteins germane to G12 and G13. Using fusion proteins in Spodoptera frugiperda (Sf9) cells and independently expressed proteins in human embryonic kidney 293 cells, and using guanosine 5'-O-(3-[35S]thio)triphosphate binding to evaluate Galpha activation directly, we found for Galpha that no ligand tested, including 8-iso-prostaglandin F (8-iso-PGF2alpha and a purported antagonist (Pinane Thromboxane A2), was silent. The activity of agonists was especially pronounced when evaluated for TPalpha-Galpha13 and in the context of receptor reserve. Agonist activity for 8-iso-PGF2 was diminished and that for pinane thromboxane A nonexistent when Galpha12 was the reporter. These data establish that G12 and G13 can report differentially potency and efficacy and underscore the relevance of receptor and G protein context.