PD 117519 (CI947)
(Synonyms: (R)-N-(2,3-二氢-1H-茚基)腺苷,CI947) 目录号 : GC30916
An adenosine receptor agonist
Cas No.:96392-15-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
PD 117519 is an adenosine receptor agonist.1 It selectively binds to adenosine A2 receptors (IC50 = 30 ?M) over A1 receptors (IC50 = 810 ?M) in rat brain membranes. PD 117519 increases heart rate and decreases systolic blood pressure in normotensive dogs when administered at doses of 2 or 10 mg/kg.2
1.Steffen, R.P.Method of treating heart failure and medicaments therefor(1987) 2.Enerson, B.E., Lin, A., Lu, B., et al.Acute drug-induced vascular injury in beagle dogs: Pathology and correlating genomic expressionToxicol. Pathol.34(1)27-32(2006)
| Cas No. | 96392-15-3 | SDF | |
| 别名 | (R)-N-(2,3-二氢-1H-茚基)腺苷,CI947 | ||
| Canonical SMILES | OC[C@@H]1[C@H]([C@H]([C@H](N2C=NC3=C2N=CN=C3N[C@@H]4CCC5=C4C=CC=C5)O1)O)O | ||
| 分子式 | C19H21N5O4 | 分子量 | 383.4 |
| 溶解度 | DMSO : ≥ 3.9 mg/mL (10.17 mM) | 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 | 2.6082 mL | 13.0412 mL | 26.0824 mL |
| 5 mM | 0.5216 mL | 2.6082 mL | 5.2165 mL |
| 10 mM | 0.2608 mL | 1.3041 mL | 2.6082 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。
Arteriopathy induced by an adenosine agonist-antihypertensive in monkeys
Toxicol Pathol.1998 May-Jun;26(3):375-80.PMID:9608643DOI: 10.1177/019262339802600311.
An adenosine agonist, designated chemically as (R)-N-(2,3-dihydro-1H-inden-1-yl) adenosine or CI-947, was administered orally to 2 males and 2 female cynomolgus monkeys each at 5, 10, 20, and 50 mg/kg of body weight for 2 wk. One male and 1 female given 50 mg/kg were euthanatized on days 10 and 8, respectively, because of poor clinical condition. Emesis was present at 10, 20, and 50 mg/kg. Decreased heart rate and QT prolongation were present at 50 mg/kg. Extramural coronary arterial lesions consisting of medial necrosis with cellular debris and mixed inflammatory cell response in the intima, media, and adventitia were present in 1 male at 20 mg/kg and 1 male at 50 mg/kg at study termination. Similar arterial lesions were present in the small and large intestines and testis of the male at 50 mg/kg. Colonic mucosal erosions with mixed inflammatory cell infiltrates in the lamina propria were seen in this male and in all CI-947 treated females at 10, 20, and 50 mg/kg. Myocardial degeneration and necrosis of myocardial fibers with mononuclear cell infiltrates in the interstititum were noted in the left ventricle of 1 female at 20 mg/kg and in all animals at 50 mg/kg. Renal cortical tubular dilatation with increases in serum creatinine and/or blood urea nitrogen were noted in a control female and animals at 10 and 50 mg/kg. Plasma CI-947 concentration increased with increasing dose. Coronary vascular injury in the monkey was similar to the arterial lesion in CI-947-treated dogs and may relate to the pharmacologic/hemodynamic effects induced by CI-947. When compared with the dog, the monkey appears to be less sensitive to development of arteriopathy, as indicated by lower incidence, at similar systemic exposure levels.
The role of eNOS phosphorylation in causing drug-induced vascular injury
Toxicol Pathol.2014 Jun;42(4):709-24.PMID:24705881DOI: 10.1177/0192623314522885.
Previously we found that regulation of eNOS is an important part of the pathogenic process of Drug-induced vascular injury (DIVI) for PDE4i. The aims of the current study were to examine the phosphorylation of eNOS in mesentery versus aorta at known regulatory sites across DIVI-inducing drug classes and to compare changes across species. We found that phosphorylation at S615 in rats was elevated 35-fold 2 hr after the last dose of CI-1044 in mesentery versus 3-fold in aorta. Immunoprecipitation studies revealed that many of the upstream regulators of eNOS activation were associated with eNOS in 1 or more signalosome complexes. Next rats were treated with drugs from 4 other classes known to cause DIVI. Each drug was given alone and in combination with SIN-1 (NO donor) or L-NAME (eNOS inhibitor), and the level of eNOS phosphorylation in mesentery and aorta tissue was correlated with the extent of vascular injury and measured serum nitrite. Drugs or combinations produced altered serum nitrite levels as well as vascular injury score in the mesentery. The results suggested that phosphorylation of S615 may be associated with DIVI activity. Studies with the species-specific A2A adenosine agonist CI-947 in rats versus primates showed a similar pattern.
Acute drug-induced vascular injury in beagle dogs: pathology and correlating genomic expression
Toxicol Pathol.2006;34(1):27-32.PMID:16507541DOI: 10.1080/01926230500512068.
Acute vascular injury that leads to vascular inflammation is a common finding in the preclinical toxicity testing of drugs in rats and dogs. However, the relevance of this finding for risk to humans is unclear. Concern about the safety of these drugs is heightened by the current lack of noninvasive clinical methods to predict the onset of vascular damage in animals or humans. Determining the relevance of this poorly understood preclinical outcome for humans requires a better understanding of the molecular mechanisms of injury in addition to the development of sensitive and specific leading biomarkers for the clinical diagnosis of acute vascular damage. Most molecular research on this toxicity has been performed in rats, but recent development of canine gene expression microarrays makes transcriptomic studies now possible in the dog. In this study, we investigated the molecular mechanisms of drug-induced vascular injury in dogs using gene arrays. After treating Beagles with toxic doses of CI-947, an adenosine receptor agonist, we profiled gene expression in the coronary arteries and correlated those changes with histopathology at 16 and 24 hours after dosing. The results demonstrated that pathobiological processes such as stimulation of the innate immune response, increased extracellular matrix turnover and oxidative stress were active at times of very early injury.
Acute cardiovascular toxicity induced by an adenosine agonist-antihypertensive in beagles
Toxicol Pathol.1991;19(2):98-107.PMID:1771371DOI: 10.1177/019262339101900203.
An adenosine agonist, designated chemically as (R)-N-(2,3-dihydro-1H-inden- 1-yl) adenosine, or CI-947, was administered to 3 male and 3 female beagles in oral doses of 5 mg/kg body weight. Multiple episodes of arrhythmia were recorded electrocardiographically with Holter monitors in 2 males and 2 females monitored up to 48 hr. One male and 1 female were necropsied at 24 hr and the remaining dogs were necropsied at 48 hr post-dosing. At 48 hr, multifocal perivascular epicardial and myocardial hemorrhage was noted grossly in 1 female. Microscopic coronary arterial alterations were present in all treated dogs irrespective of the occurrence of arrhythmias. At 24 hr, proteinic material and red cells were present in the media accompanied by minimal adventitial accumulation of neutrophils. At 48 hr, coronary arterial lesions progressed to media vacuolation, transmural necrosis, and perivascular accumulation of neutrophils. Ultrastructural alterations included: endothelial retraction, subendothelial accumulation of fibrin and platelets, necrosis of smooth muscle cells, and mural infiltration of granulocytes and monocytes. Coronary vascular injury may be due to altered hemodynamics associated with the coronary vasodilator properties of adenosine agonist compounds.