GS-6201
(Synonyms: 3-乙基-1-丙基-8-(1-(3-(三氟甲基)苄基)-1H-吡唑-4-基)-1H-嘌呤-2,6(3H,8H)-二酮,CVT-6883) 目录号 : GC38789
An adenosine A2B receptor antagonist
Cas No.:752222-83-6
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
CVT-6883 is an adenosine A2B receptor antagonist (Ki = 22 nM).1 It is selective for adenosine A2B over adenosine A1, A2A, and A3 receptors (Kis = 1,940, 3,280, and 1,070 nM, respectively), as well as a panel of 84 receptors, ion channels, transporters, and enzymes at 10 ?M. CVT-6883 (6 mg/kg) decreases allergen challenge-induced bronchoalveolar lavage fluid (BALF) eosinophil and lymphocyte infiltration and airway reactivity in a mouse model of allergic asthma.2 It also decreases fibrosis in the non-infarct zone, improves ejection fractions, and reduces ventricular tachycardia in a rat model of myocardial infarction.3
1.Elzein, E., Kalla, R.V., Li, X., et al.Discovery of a novel A2B adenosine receptor antagonist as a clinical candidate for chronic inflammatory airway diseasesJ. Med. Chem.51(7)2267-2278(2008) 2.Mustafa, S.J., Nadeem, A., Fan, M., et al.Effect of a specific and selective A2B adenosine receptor antagonist on adenosine agonist AMP and allergen-induced airway responsiveness and cellular influx in a mouse model of asthmaJ. Pharmacol. Exp. Ther.320(3)1246-1251(2007) 3.Zhang, H., Zhong, H., Everett, T.H., 4th, et al.Blockade of A2B adenosine receptor reduces left ventricular dysfunction and ventricular arrhythmias 1 week after myocardial infarction in the rat modelHeart Rhythm11(1)101-109(2014)
| Cas No. | 752222-83-6 | SDF | |
| 别名 | 3-乙基-1-丙基-8-(1-(3-(三氟甲基)苄基)-1H-吡唑-4-基)-1H-嘌呤-2,6(3H,8H)-二酮,CVT-6883 | ||
| Canonical SMILES | O=C(N(CCC)C1=O)N(CC)C(C1=N2)=NC2C3=CN(N=C3)CC4=CC=CC(C(F)(F)F)=C4 | ||
| 分子式 | C21H21F3N6O2 | 分子量 | 446.43 |
| 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 | 2.24 mL | 11.2 mL | 22.3999 mL |
| 5 mM | 0.448 mL | 2.24 mL | 4.48 mL |
| 10 mM | 0.224 mL | 1.12 mL | 2.24 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。
GS-6201, a selective blocker of the A2B adenosine receptor, attenuates cardiac remodeling after acute myocardial infarction in the mouse
J Pharmacol Exp Ther 2012 Dec;343(3):587-95.PMID:22923737DOI:10.1124/jpet.111.191288.
Adenosine (Ado) is released in response to tissue injury, promotes hyperemia, and modulates inflammation. The proinflammatory effects of Ado, which are mediated by the A(2B) Ado receptor (AdoR), may exacerbate tissue damage. We hypothesized that selective blockade of the A(2B) AdoR with 3-ethyl-1-propyl-8-(1-(3-trifluoromethylbenzyl)-1H-pyrazol-4-yl)-3,7-dihydropurine-2,6-dione (GS-6201) during acute myocardial infarction (AMI) would reduce adverse cardiac remodeling. Male ICR mice underwent coronary artery ligation or sham surgery (n = 10-12 per group). The selective A(2B) AdoR antagonist GS-6201 (4 mg/kg) was given intraperitoneally twice daily starting immediately after surgery and continuing for 14 days. Transthoracic echocardiography was performed before surgery and after 7, 14, and 28 days. A subgroup of mice was killed 72 h after surgery, and the activity of caspase-1, a key proinflammatory mediator, was measured in the cardiac tissue. All sham-operated mice were alive at 4 weeks, whereas 50% of vehicle-treated mice and 75% of GS-6201-treated mice were alive at 4 weeks after surgery. Compared with vehicle, treatment with GS-6201 prevented caspase-1 activation in the heart at 72 h after AMI (P < 0.001) and significantly limited the increase in left ventricular (LV) end-diastolic diameter by 40% (P < 0.001), the decrease in LV ejection fraction by 18% (P < 0.01) and the changes in the myocardial performance index by 88% (P < 0.001) at 28 days after AMI. Selective blockade of A(2B) AdoR with GS-6201 reduces caspase-1 activity in the heart and leads to a more favorable cardiac remodeling after AMI in the mouse.
Blockade of A2B adenosine receptor reduces left ventricular dysfunction and ventricular arrhythmias 1 week after myocardial infarction in the rat model
Heart Rhythm 2014 Jan;11(1):101-9.PMID:24120874DOI:10.1016/j.hrthm.2013.10.023.
Background: Remodeling occurs after myocardial infarction (MI), leading to fibrosis, dysfunction, and ventricular tachycardias (VTs). Adenosine via the A2B adenosine receptor (A2BAdoR) has been implicated in promoting fibrosis. Objective: To determine the effects of GS-6201, a potent antagonist of the A2BAdoR, on arrhythmogenic and functional cardiac remodeling after MI. Methods: Rats underwent ischemia-reperfusion MI and were randomized into 4 groups: control (treated with vehicle), angiotensin-converting enzyme inhibitor (treated with enalapril 1 day after MI), GS-6201-1d (treated with GS-6201 1 day after MI), GS-6201-1w (treated with GS-6201 administered 1 week after MI) . Echocardiography was performed at baseline and 1 and 5 weeks after MI. Optical mapping, VT inducibility, and histologic analysis were conducted at follow-up. Results: Treatment with the angiotensin-converting enzyme inhibitor improved ejection fraction (57.8% ± 2.5% vs 43.3% ± 1.7% in control; P < .01), but had no effect on VT inducibility. Treatment with GS-6201 improved ejection fraction (55.6% ± 2.6% vs 43.3% ± 1.7% in control; P < .01) and decreased VT inducibility (9.1% vs 68.4% in control; P < .05). Conduction velocities were significantly higher at border and infarct zones in hearts of rats treated with GS-6201 than in those of other groups. The conduction heterogeneity index was also significantly lower in hearts of rats treated with GS-6201. Histologic analysis showed that while both GS-6201 and enalapril decreased fibrosis in the noninfarct zone, only GS-6201 reduced the heterogeneity of fibrosis at the border, which is consistent with its effect on VT reduction. Conclusions: Treatment with an A2BAdoR antagonist at 1 week results in the improvement in cardiac function and decreased substrate for VT. The inhibition of fibrogenesis by A2BAdoR antagonists may be a new target for the prevention of adverse remodeling after MI.
The A2B adenosine receptor modulates pulmonary hypertension associated with interstitial lung disease
FASEB J 2012 Jun;26(6):2546-57.PMID:22415303DOI:10.1096/fj.11-200907.
Development of pulmonary hypertension is a common and deadly complication of interstitial lung disease. Little is known regarding the cellular and molecular mechanisms that lead to pulmonary hypertension in patients with interstitial lung disease, and effective treatment options are lacking. The purpose of this study was to examine the adenosine 2B receptor (A(2B)R) as a regulator of vascular remodeling and pulmonary hypertension secondary to pulmonary fibrosis. To accomplish this, cellular and molecular changes in vascular remodeling were monitored in mice exposed to bleomycin in conjunction with genetic removal of the A(2B)R or treatment with the A(2B)R antagonist GS-6201. Results demonstrated that GS-6201 treatment or genetic removal of the A(2B)R attenuated vascular remodeling and hypertension in our model. Furthermore, direct A(2B)R activation on vascular cells promoted interleukin-6 and endothelin-1 release. These studies identify a novel mechanism of disease progression to pulmonary hypertension and support the development of A(2B)R antagonists for the treatment of pulmonary hypertension secondary to interstitial lung disease.