GP531
目录号 : GC32675
GP531是一种有效的第二代腺苷(adenosine)调节剂，在基础条件下药理学沉默，但在缺血期间增加局部内源性腺苷。
Cas No.:142344-87-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Rabbits: Baseline hemodynamic parameters and temperature are obtained. The rabbits are randomized to 1 of 3 groups: a low dose of GP531, a high dose of GP 531, or vehicle (10% sodium metabisulfite). The low dose consists of a loading dose of 700 mg/kg given over 10 minutes starting at 12 minutes before coronary artery occlusion, followed by an infusion of 10 mg/kg per minute for the duration of the study. The high dose consists of a loading dose of 2100 mg/kg given over 10 minutes starting at 12 minutes before CAO followed by an infusion of 30 mg/kg per min for the duration of the study. All rabbits receive the same volume (12 mL over the duration of the study), so the concentrations are adjusted for body weight. The rabbits are then subjected to 30 minutes of coronary artery occlusion. The coronary artery is occluded by tightening the snare. Regional myocardial blood flow is measured during the ischemic period at 25 minutes of CAO[1]. Dog: Six dogs with intracoronary microembolizationinduced HF receive a constant intravenous infusion of GP531 (10 μg/kg/min) or vehicle (normal saline) for 6 h in random order 1 week apart. Hemodynamic measurements are made at baseline and at 1, 2, 3, 4, 5 and 6 h after initiating drug infusion. Myocardial oxygen consumption (MVO2) is measured at baseline and 4 and 6 h. LV pressure-volume relationship (PVR) is measured at baseline and 6 h[2]. |
References: [1]. Hale SL, et al. Cardioprotection with adenosine-regulating agent, GP531: effects on no-reflow, infarct size, and blood flow following ischemia/ reperfusion in the rabbit. J Cardiovasc Pharmacol Ther. 2010 Mar;15(1):60-7. | |
GP531 is a potent, second-generation adenosine regulating agent, is pharmacologically silent under basal conditions but increases localized endogenous adenosine during ischemia.
Low-dose GP531 reduces infarct size by 34% compared with vehicle and reduces the extent of the anatomic no-reflow zone by 31% compared with vehicle. Infarct size and zone of no-reflow in the high dose are reduced by 22% and 16%, respectively. GP531 does not affect hemodynamics or blood flow. GP531 is effective at the lower dose in reducing the severity of ischemic/reperfusion injury, without inducing the adverse hemodynamic effects associated with adenosine administration such as bradycardia and hypotension[1]. GP531 infusion has no effect on heart rate or mean aortic pressure but significantly decreases left ventricular end-diastolic pressure, end-diastolic volume, end-systolic volume and end-diastolic wall stress. GP531 significantly increases left ventricular EF, deceleration time of early mitral inflow velocity and the slope of end-systolic PVR without increasing MVO2[2].
[1]. Hale SL, et al. Cardioprotection with adenosine-regulating agent, GP531: effects on no-reflow, infarct size, and blood flow following ischemia/ reperfusion in the rabbit. J Cardiovasc Pharmacol Ther. 2010 Mar;15(1):60-7. [2]. Wang M, et al. Acute intravenous infusion of an adenosine regulating agent improves left ventricular function in dogs with advanced heart failure. Cardiovasc Drugs Ther. 2013 Dec;27(6):489-98.
| Cas No. | 142344-87-4 | SDF | |
| Canonical SMILES | O=C(C1=C(N)N([C@H]2[C@@H]([C@@H]([C@@H](CNCC3=CC=CC=C3)O2)O)O)C=N1)N | ||
| 分子式 | C16H21N5O4 | 分子量 | 347.37 |
| 溶解度 | DMSO: 125 mg/mL (359.85 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 | 2.8788 mL | 14.3939 mL | 28.7877 mL |
| 5 mM | 0.5758 mL | 2.8788 mL | 5.7575 mL |
| 10 mM | 0.2879 mL | 1.4394 mL | 2.8788 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 | ||||||||||
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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.
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Cardioprotection with adenosine-regulating agent, GP531: effects on no-reflow, infarct size, and blood flow following ischemia/ reperfusion in the rabbit
J Cardiovasc Pharmacol Ther 2010 Mar;15(1):60-7.PMID:20133497DOI:10.1177/1074248409357742.
GP531, a potent, second-generation adenosine-regulating agent, is pharmacologically silent under basal conditions but increases localized endogenous adenosine during ischemia. GP531 improves functional recovery after myocardial ischemia, but its effects on infarct size and no-reflow have not been reported. The objective was to determine whether GP531 reduces necrosis and the anatomic no-reflow defect and to evaluate its effects on regional myocardial blood flow (RMBF). GP531 was given as a loading dose plus infusion at 2 doses (700 microg/kg and 10 microg/kg per minute or 2100 microg/kg and 30 microg/kg per minute) or vehicle, starting 12 minutes before a 30-minute coronary occlusion and throughout 3 hours reperfusion in rabbits. Risk zone was delineated by blue dye, necrosis by tetrazolium staining, RMBF by radioactive microspheres, and no-reflow defect by thioflavin S. The extent of the ischemic risk zone was similar in all groups. Low-dose GP531 reduced infarct size by 34% (0.33 +/- 0.4 of the risk zone) compared with vehicle (0.50 +/- 0.4, P < .01) and reduced the extent of the anatomic no-reflow zone by 31% compared with vehicle (0.25 +/- 0.3 of the risk zone vs 0.36 +/- 0.4 in the vehicle group, P < .05). Infarct size and zone of no-reflow in the high dose were reduced by 22% and 16%, respectively (P = NS vs the other 2 groups). GP531 did not affect hemodynamics or blood flow. Thus, GP531 was effective at the lower dose evaluated in this study, reducing the severity of ischemic/reperfusion injury, without inducing the adverse hemodynamic effects associated with adenosine administration such as bradycardia and hypotension.
Spectrophotometric determination of the cardioprotective drug GP531 in human plasma
J Biochem Biophys Methods 1996 Oct 15;33(1):25-30.PMID:8905465DOI:10.1016/0165-022x(96)00011-5.
A simple spectrophotometric assay has been developed for determining concentrations of the new cardioprotective agent, GP531, in human plasma. The method is adapted from the Bratton-Marshall assay (BMA) for the detection of primary aromatic amines. The assay can be used to measure plasma concentrations of the drug during i.v. infusion administration to patients. The limit of quantitation of the assay is 1 microgram/ml using a 0.8 ml sample ultrafiltrate of plasma. The colorimetric assay correlates well with a previously described high performance liquid chromatographic (HPLC) procedure.
A sensitive assay for the aminoimidazole-containing drug GP531 in plasma using liquid chromatography with amperometric electrochemical detection: a new class of electroactive compounds
J Pharm Biomed Anal 1996 Aug;14(11):1535-8.PMID:8877860DOI:10.1016/0731-7085(95)01719-4.
Aminoimidazole-containing compounds have been found to be electroactive and can be detected by amperometric electrochemical detection (ECD) with a high degree of sensitivity. A liquid chromatography (LC) method using ECD was developed for measuring plasma concentrations of the aminoimidazole-containing drug GP531, a potent adenosine-regulating agent. Plasma samples were extracted with 2-propanol and analyzed by LC under isocratic conditions using a mobile phase of methanol-sodium phosphate (pH 6.3; 3.3 mM) (32:68, v/v). The potential of the glassy carbon working electrode was set at +800 mV. The limit of quantitation was 12.5 ng ml-1 of GP531 using 100 microliters of plasma. The method was used to define the pharmacokinetics of GP531 in monkey following i.v. administration.
Cardioprotection with a novel adenosine regulating agent mediated by intravascular adenosine
Eur J Pharmacol 1997 Mar 19;322(2-3):211-20.PMID:9098689DOI:10.1016/s0014-2999(97)00011-3.
Adenosine is cardioprotective in models of myocardial stunning and infarction, but the precise compartment within the heart in which adenosine elicits its cardioprotective effects has not been determined. The goals of the present study were to (i) investigate the effects of a novel adenosine regulating agent, GP531 (5-amino-1-beta-n-(5-benzylamino-5-deoxyribofuranosyl) imidazole-4-carboxamide), on post-ischemic myocardial function, and (ii) examine the contribution of endogenous adenosine in the intravascular and interstitial compartments in mediating the beneficial effects. Pigs were instrumented for measurement of myocardial segment shortening, and for sampling of coronary venous blood and myocardial interstitial fluid for determination of adenosine concentration. Myocardial dysfunction was induced by 4 x 8 min coronary occlusions, and recovery of regional function was monitored for 2 h. In control pigs, function recovered to 24 +/- 2% of baseline after 2 h. Treatment with GP531 improved functional recovery to 55 +/- 3%. GP531-mediated cardioprotection was prevented by adenosine receptor blockade with 8-sulfophenyltheophylline (23 +/- 2%). GP531 did not affect basal adenosine levels, but caused a 2-fold greater increase in vascular adenosine concentration with ischemia (54.6 +/- 10.6 vs. 28.1 +/- 8.0 microM in controls. P < 0.05). In contrast, the interstitial adenosine concentration was not significantly different in treated vs. untreated control pigs (9.4 +/- 3.9 vs. 15.0 +/- 1.8 microM in controls). These data indicate that (1) GP531 improves recovery of myocardial function following ischemia reperfusion injury via an adenosine receptor-dependent mechanism, and (2) the cardioprotection is associated with increased intravascular, but not interstitial, adenosine concentration during ischemia. Therefore, we conclude that cardioprotection elicited by GP531-enhanced endogenous adenosine is dependent on an intravascular site of action.
Acute intravenous infusion of an adenosine regulating agent improves left ventricular function in dogs with advanced heart failure
Cardiovasc Drugs Ther 2013 Dec;27(6):489-98.PMID:23907235DOI:10.1007/s10557-013-6482-9.
Purpose: GP531 is a second generation adenosine regulating agent (ARA) that increases concentrations of endogenous adenosine, a natural cardioprotective agent, in ischemic/hypoxic tissue. This study examined the effects of acute intravenous infusions of GP531 on left ventricular (LV) systolic and diastolic function in dogs with advanced chronic heart failure (HF) (LV ejection fraction, EF <30 %). Methods: Six dogs with intracoronary microembolization-induced HF received a constant intravenous infusion of GP531 (10 μg/kg/min) or vehicle (normal saline) for 6 h in random order 1 week apart. Hemodynamic measurements were made at baseline and at 1, 2, 3, 4, 5 and 6 h after initiating drug infusion. Myocardial oxygen consumption (MVO2) was measured at baseline and 4 and 6 h. LV pressure-volume relationship (PVR) was measured at baseline and 6 h. Results: Vehicle infusions had no effect on indexes of LV systolic and diastolic function. GP531 infusion had no effect on heart rate or mean aortic pressure but significantly decreased LV end-diastolic pressure, end-diastolic volume, end-systolic volume and end-diastolic wall stress. GP531 significantly increased LV EF (27 ± 1 at baseline to 34 ± 1 after 6 h of drug infusion, p < 0.05), deceleration time of early mitral inflow velocity and the slope of end-systolic PVR without increasing MVO2. Conclusions: Results of the study indicate that approaches which increase the local release of adenosine in failing LV myocardium, such as ARAs, have a favorable impact on LV performance. These observations support the continued development of ARA's for the treatment of acute HF syndromes.