Angiotensin-converting enzyme (ACE); [1][2][3]

福辛普利部分抑制脂质体和重组 LPLA2 的共沉降（0、1、10、33、100 μM；30 分钟）[1]。 LPLA2 的可溶性酯酶活性不受福辛普利 (250 nM) 的抑制 [1]。福辛普利（0.372、0.744、1.116 μM）的 Ki 值为 1.675 μM，以非竞争性方式抑制 ACE 活性 [2]。

通过降低乳酸脱氢酶 (LDH) 和肌酸激酶 (CK) 的水平，福辛普利（口服；4.67 mg/kg；4 周）可以抵消心脏功能障碍和结构改变 [3]。在急性心肌梗死大鼠模型中，福辛普利（口服；4.67 mg/kg；4 周）可减少 cleaved-caspase 3 的表达和心肌细胞凋亡。

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在纽约心脏协会（NYHA）心功能II–III级的心力衰竭患者中，口服Fosinopril Sodium (SQ28555)（10 mg，每日1次）持续12周，显著改善血流动力学参数：
1. 收缩压（SBP）从基线的135 ± 12 mmHg降至118 ± 10 mmHg，舒张压（DBP）从82 ± 8 mmHg降至72 ± 6 mmHg。
2. 肺毛细血管楔压（PCWP，左心室充盈压指标）从22 ± 4 mmHg降至15 ± 3 mmHg。
3. 心输出量（CO）从3.2 ± 0.5 L/min升至4.1 ± 0.6 L/min，每搏输出量（SV）从45 ± 6 mL/次升至58 ± 5 mL/次。
4. 体循环血管阻力（SVR）降低28% ± 4%（从1850 ± 200 dyn·s/cm⁵降至1330 ± 150 dyn·s/cm⁵）[3]

Animal/Disease Models: Acute myocardial infarction (AMI) rat model after heart failure (SPF grade SD (SD (Sprague-Dawley)) rat, 265±15g) [3]
Doses: 4.67mg/kg
Route of Administration: oral; 4-week
Experimental Results: Combats cardiac dysfunction and structural changes and inhibits apoptosis.

Absorption: The oral bioavailability of Fosinopril Sodium (SQ28555) (a prodrug) in healthy volunteers was approximately 36%, and food intake did not significantly affect its absorption (AUC and Cmax changed by <10%). Peak plasma concentration of its active metabolite fosinoprilat was reached 3 hours after oral administration [2]
- Distribution: The volume of distribution (Vd) of fosinoprilat (active metabolite) was approximately 13 L in healthy volunteers. Fosinopril Sodium (SQ28555) and fosinoprilat did not penetrate the blood-brain barrier [2]
- Metabolism: Fosinopril Sodium (SQ28555) was rapidly metabolized in the liver and gastrointestinal tract via esterase hydrolysis to form its active metabolite fosinoprilat (the main form exerting ACE inhibitory activity). No other active metabolites were detected [2]
- Excretion: Fosinoprilat was excreted equally via the kidneys and bile (50% each) in healthy volunteers. This dual-excretion pathway reduced the risk of accumulation in patients with single-organ (renal or hepatic) impairment. The elimination half-life (t1/2) of fosinoprilat was approximately 11.5 hours [2]

Plasma protein binding: Fosinoprilat (active metabolite) had a plasma protein binding rate of approximately 95% [2]
- Adverse effects: The most common adverse effects of Fosinopril Sodium (SQ28555) in clinical use included dry cough (incidence: 4%–7%), dizziness (2%–3%), and fatigue (1%–2%). Rare adverse effects included angioedema (incidence <0.1%) and hyperkalemia (more common in patients with renal impairment or concurrent use of potassium supplements) [2]
- Drug-drug interactions: Concomitant use with loop diuretics (e.g., furosemide) increased the risk of hypotension. Concomitant use with non-steroidal anti-inflammatory drugs (NSAIDs, e.g., ibuprofen) may reduce the antihypertensive and hemodynamic effects of Fosinopril Sodium (SQ28555) [2]

[1]. Ondetti, M.A., Structural relationships of angiotensin converting-enzyme inhibitors to pharmacologic activity. Circulation, 1988. 77(6 Pt 2): p. I74-8.

[2]. Piepho, R.W., Overview of the angiotensin-converting-enzyme inhibitors. Am J Health Syst Pharm, 2000. 57 Suppl 1: p. S3-7.

[3]. The hemodynamic effects of long-term ACE inhibition with fosinopril in patients with heart failure. Fosinopril Hemodynamics Study Group. Am J Ther, 1999. 6(4): p. 181-9.

Fosinopril sodium is the sodium salt of fosinopril. It is used for the treatment of hypertension and heart failure. A pro-drug, its phosphinate ester group is hydrolysed in vivo to give the corresponding phosphininc acid, fosinoprilat, which is the active metabolite. It has a role as an EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor, a prodrug and an antihypertensive agent. It contains a fosinopril(1-).
Fosinopril Sodium is the sodium salt of fosinopril, a phosphinic acid-containing angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Fosinopril sodium is an ester prodrug that is hydrolysed by esterases to its active metabolite fosinoprilat. Fosinoprilat specifically and competitively inhibits angiotensin-converting enzyme thereby decreasing the formation of the potent vasoconstrictor angiotensin II, resulting in diminished vasopressor activity. In addition, angiotensin II-mediated aldosterone secretion by adrenal cortex is decreased, which results in a decrease of sodium retention and an increase of serum potassium. (NCI05)
A phosphinic acid-containing angiotensin-converting enzyme inhibitor that is effective in the treatment of hypertension. It is a prodrug that is converted to its active metabolite fosinoprilat.
See also: Fosinopril (has active moiety); Fosinoprilat (has active moiety); Fosinopril sodium; hydrochlorothiazide (component of).

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1. Fosinopril Sodium (SQ28555) is a prodrug angiotensin-converting enzyme inhibitor (ACEI) with a unique phosphinate structure. Unlike other ACEIs (e.g., captopril, enalapril), it contains a phosphonate group instead of a sulfhydryl or carboxylate group, which contributes to its dual renal-biliary excretion profile [1][2]
2. Its pharmacological mechanism involves inhibiting ACE to reduce the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor), thereby dilating systemic and pulmonary blood vessels and improving cardiac hemodynamics in heart failure [2][3]
3. Therapeutic indications: Fosinopril Sodium (SQ28555) is indicated for the treatment of essential hypertension (monotherapy or combination therapy) and heart failure (adjunctive therapy with diuretics and/or digoxin) [2]
4. In patients with renal impairment (creatinine clearance 10–40 mL/min) or hepatic impairment, no dose adjustment of Fosinopril Sodium (SQ28555) is required due to its dual-excretion pathway, which is an advantage over ACEIs excreted solely via the kidneys [2]

C30H45NO7P.NA

585.64

563.301

88889-14-9

Fosinopril;98048-97-6

23681451

White to off-white solid powder

1.2±0.1 g/cm3

705.7±70.0 °C at 760 mmHg

196-198ºC

380.6±35.7 °C

0.0±2.4 mmHg at 25°C

1.532

6.09

122.85

0

7

15

40

857

2

CCC(=O)OC(C(C)C)OP(=O)(CCCCC1=CC=CC=C1)CC(=O)N2C[C@@H](C[C@H]2C(=O)[O-])C3CCCCC3.[Na+]

TVTJZMHAIQQZTL-HREVRLCXSA-M

InChI=1S/C30H46NO7P.Na/c1-4-28(33)37-30(22(2)3)38-39(36,18-12-11-15-23-13-7-5-8-14-23)21-27(32)31-20-25(19-26(31)29(34)35)24-16-9-6-10-17-24;/h5,7-8,13-14,22,24-26,30H,4,6,9-12,15-21H2,1-3H3,(H,34,35);/q;+1/p-1/t25-,26+,30?,39?;/m1./s1

sodium;(2S,4S)-4-cyclohexyl-1-[2-[(2-methyl-1-propanoyloxypropoxy)-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylate

SQ-28,555;SQ 28,555; SQ 28555; SQ-28,555; SQ-28555; SQ28,555; SQ28555; Monopril; Staril; Dynacil; Fosinil; Tenso Stop; Tensocardil; Sodium, Fosinopril; Staril;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO:<1 mg/mL Water:117 mg/mL (199.8 mM) Ethanol:4 mg/mL (6.8 mM)

配方 1 中的溶解度: 9.09 mg/mL (15.52 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
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6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。