Zofenopril
(Synonyms: 1-萘乙酸) 目录号 : GC37972
A prodrug form of zofenoprilat
Cas No.:81872-10-8
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
Zofenopril is a prodrug form of the angiotensin-converting enzyme (ACE) inhibitor zofenoprilat.1 Zofenopril is hydrolyzed by cardiac esterases in vivo to form zofenoprilat. It inhibits ACE with an IC50 value of 0.9 nM in heart tissue homogenates and inhibits cardiac ACE activity in isolated perfused rat hearts. It reduces mean arterial blood pressure in two kidney-one clip renal hypertensive (2K-1C) rats and spontaneously hypertensive rats (SHRs) when administered at doses of 2.2, 6.6, and 22 mg/kg.2 Unlike the ACE inhibitor ramipril , zofenopril does not affect bronchoalveolar lavage fluid (BALF) levels of bradykinin or prostaglandin E2 or increase coughing induced by citric acid in guinea pigs.3
1.Grover, G.J., Sleph, P.G., Dzwonczyk, S., et al.Effects of different angiotensin-converting enzyme (ACE) inhibitors on ischemic isolated rat hearts: Relationship between cardiac ACE inhibition and cardioprotectionJ. Pharmacol. Exp. Ther.257(3)919-929(1991) 2.DeForrest, J.M., Waldron, T.L., Krapcho, J., et al.Preclinical pharmacology of zofenopril, an inhibitor of angiotensin I converting enzymeJ. Cardiovasc. Pharmacol.13(6)887-894(1989) 3.Cialdai, C., Giuliani, S., Valenti, C., et al.Differences between zofenopril and ramipril, two ACE inhibitors, on cough induced by citric acid in guinea pigs: Role of bradykinin and PGE2Naunyn Schmiedebergs Arch. Pharmacol.382(5-6)455-461(2010)
| Cas No. | 81872-10-8 | SDF | |
| 别名 | 1-萘乙酸 | ||
| Canonical SMILES | O=C(O)[C@H]1N(C([C@H](C)CSC(C2=CC=CC=C2)=O)=O)C[C@@H](SC3=CC=CC=C3)C1 | ||
| 分子式 | C22H23NO4S2 | 分子量 | 429.55 |
| 溶解度 | DMSO: 5 mg/mL (11.64 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 | 2.328 mL | 11.6401 mL | 23.2802 mL |
| 5 mM | 0.4656 mL | 2.328 mL | 4.656 mL |
| 10 mM | 0.2328 mL | 1.164 mL | 2.328 mL |
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| 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，
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1. 首先保证母液是澄清的；
2.
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Efficacy of Zofenopril Alone or in Combination with Hydrochlorothiazide in Patients with Kidney Dysfunction
Curr Clin Pharmacol 2019;14(1):5-15.PMID:30360726DOI:10.2174/1574884713666181025145404.
Hypertension and kidney disease often coexist, further increasing the risk of future cardiovascular events. Treatment of hypertensive adults with an angiotensin converting enzyme inhibitor in case of concomitant kidney disease may slow disease progression. The third-generation liphophilic angiotensin converting enzyme inhibitor Zofenopril, administered alone or combined with a thiazide diuretic, has proved to be effective in lowering blood pressure in hypertensive patients and to reduce the risk of fatal and non-fatal events in post-acute myocardial infarction and heart failure. In almost three-hundred hypertensive patients with kidney impairment Zofenopril administered for 12 weeks showed a similar blood pressure-lowering effect irrespective of the stage of the disease, with larger effects in combination with a thiazide diuretic, particularly in patients with slightly or moderately impaired kidney function. In animal models, Zofenopril produced a significant and long-lasting inhibition of kidney angiotensin converting enzyme inhibitor and prevented kidney morphological and functional alterations following kidney ischemia-reperfusion injury. Treatment of hypertensive patients for 18 weeks with a combination of Zofenopril 30 mg and hydrochlorothiazide 12.5 mg resulted in a reduction in albumin creatinine ratio of 8.4 mg/g (49.6% reduction from baseline values) and no changes in glomerular filtration rate, variations in line with those obtained in the control group treated with a combination of irbesartan 150 mg and hydrochlorothiazide 12.5 mg. Thus, some preliminary evidence exists to support that relatively long-term treatment with the angiotensin converting enzyme inhibitor Zofenopril alone or combined with hydrochlorothiazide is effective in controlling blood pressure and may confer some kidney protection due to ACE inhibition properties.
Zofenopril: Blood pressure control and cardio-protection
Cardiol J 2022;29(2):305-318.PMID:34622438DOI:10.5603/CJ.a2021.0113.
Current hypertension guidelines suggest various strategies to reduce blood pressure levels, thereby reducing cardiovascular events: combinations of drugs with different mechanisms of action, such as an angiotensin converting enzyme inhibitors (ACEIs) and a diuretic, are the cornerstone of the modern treatment of hypertension, also as initial therapy. Among ACEIs, Zofenopril has been shown to be effective in the management of hypertension both as monotherapy and in combination with a diuretic: Zofenopril/hydrochlorothiazide fixed dose combination is particularly useful to improve treatment adherence through simplification of treatment regimen. Moreover, thanks to the sulfhydryl group, Zofenopril has some peculiar properties (higher lipophilicity and tissue penetration, lower bradykinin-dependent effect, higher affinity for, and more persistent binding to, tissue ACE, significant antioxidant effect), which may account for the cardioprotective effects of the drug demonstrated in both pre-clinical studies and randomized clinical trials. The positive impact of Zofenopril on clinical outcomes has been extensively documented by the SMILE program, including several clinical trials in patients with different conditions of myocardial ischemia treated with Zofenopril: the results of the SMILE program, demonstrating the benefits of Zofenopril vs. placebo and other ACEIs, emphasize the importance of a differentiated approach to patients with ischemic heart disease, based on a careful choice of the adopted agent, in order to improve the overall impact of pharmacological treatment on clinical outcomes.
Zofenopril plus hydrochlorothiazide: Combination therapy for the treatment of mild to moderate hypertension
Drugs 2006;66(8):1107-15.PMID:16789795DOI:10.2165/00003495-200666080-00006.
Achieving target blood pressure (BP) levels in clinical practice is one of the main challenges for physicians in the management of patients with hypertension. It is now recognised that the majority of patients will require at least two antihypertensive drugs to achieve optimal BP control; the use of combination therapy as first-line treatment is also increasing as BP goals of antihypertensive therapy become more ambitious. The fixed combination of Zofenopril/hydrochlorothiazide (HCTZ) 30/12.5 mg/day is approved in Italy, France, Switzerland and Greece for the management of mild to moderate hypertension. In clinical trials comparing Zofenopril/HCTZ with each agent administered as monotherapy, combination therapy was more effective in normalising BP. This effect was particularly evident in one trial in which patients who were nonresponsive to Zofenopril monotherapy were studied. In addition, in clinical trials to date, combination therapy provided sustained and consistent BP control over the entire 24-hour dose interval. Despite the greater efficacy of Zofenopril/HCTZ 30/12.5 mg/day, when directly compared with each agent administered as monotherapy, there were no significant differences in the nature, severity or incidence of treatment-related adverse events; headache, dizziness, cough and polyuria were most frequently reported. Notably, in one study, fewer patients discontinued treatment with combination therapy than with Zofenopril monotherapy due to adverse events. In conclusion, Zofenopril/HCTZ 30/12.5 mg/day provides more optimal BP control in a larger proportion of patients than would be achievable with monotherapy, while maintaining the tolerability profile observed with each individual agent, and thereby potentially enhancing patient compliance. The efficacy and safety profiles of this combination shown in clinical trials to date indicate that it will be a useful addition to currently available therapy for patients who have mild to moderate hypertension that is not adequately controlled by monotherapy, as well as for patients who require more rapid, intensive BP control.
Efficacy and Safety of Zofenopril Versus Ramipril in the Treatment of Myocardial Infarction and Heart Failure: A Review of the Published and Unpublished Data of the Randomized Double-Blind SMILE-4 Study
Adv Ther 2018 May;35(5):604-618.PMID:29667144DOI:10.1007/s12325-018-0697-x.
Zofenopril is a lipophilic, sulfhydryl group-containing angiotensin-converting enzyme (ACE)-inhibitor, characterized by wide tissue distribution, long duration of action, and pleiotropic effects on endothelial dysfunction. Its clinical efficacy and safety have been described in the four randomized controlled trials of the SMILE program, which globally enrolled more than 3600 patients in post-acute myocardial infarction (AMI) setting. The SMILE-4 study specifically selected patients with left ventricular dysfunction at admission, and compared the effects of Zofenopril or ramipril in combination with acetylsalicylic acid (ASA). Zofenopril demonstrated its superiority over ramipril in reducing the combined occurrence of death or hospitalization for cardiovascular causes both in the overall population included in the original study and in subgroups of patients at highest risk, namely hypertensive and diabetic subjects. The effects of the early treatment with Zofenopril were sustained over time, and, after 5 years of follow-up, Zofenopril increased the survival likelihood and reduced the hospitalization rate. Compared to ramipril, Zofenopril was cost-effective with a number to treat of 13 and an incremental cost-effectiveness ratio (ICER) of 2125.45 euros for any additional event prevented. Furthermore, in real-world settings, Zofenopril decreased the risk of death in patients with heart failure, particularly in men, and in subjects older than 76 years or with ejection fraction lower than 54%. These results support the early use of Zofenopril immediately after AMI, even in the presence of comorbidities, and its maintenance over time to reduce the risk of heart failure. Funding: Menarini International Operations Luxembourg S.A.
Zofenopril plus hydrochlorothiazide combination in the treatment of hypertension: an update
Expert Rev Cardiovasc Ther 2014 Sep;12(9):1055-65.PMID:25098297DOI:10.1586/14779072.2014.946405.
The fixed combination of Zofenopril 30 mg plus hydrochlorothiazide 12.5 mg is indicated for the management of hypertensive patients whose blood pressure (BP) is not adequately controlled on Zofenopril alone. In clinical trials, this combination therapy proved to be superior to monotherapy in reducing office and ambulatory BP. In this review, the authors have updated the current evidence on the efficacy of the Zofenopril plus hydrochlorothiazide combination in light of the results of the recent ZODIAC study on previously monotherapy-treated uncontrolled hypertensive patients with associated cardiovascular risk factors. The trial documented a similar BP control under this combination and with irbesartan plus hydrochlorothiazide, but a larger reduction of high-sensitivity C-reactive protein, suggesting a potential protective effect against vascular inflammation. Thus, the fixed combination of Zofenopril plus hydrochlorothiazide may have a particular place in the treatment of high-risk or monotherapy-treated uncontrolled hypertensive patients requiring a more prompt, intensive and sustained BP reduction, as recommended by the current guidelines.