福辛普利（0-100 μM；30 分钟）部分抑制脂质体和重组 LPLA2 的共沉降 [1]。福辛普利 (250 nM) 对 LPLA2 可溶性酯酶活性没有抑制作用 [1]。 ACE 活性被福辛普利（0.372、0.744、1.116 μM）非竞争性抑制，Ki 值为 1.675 μM [2]。

给予福辛普利（4.67 mg/kg；口服；4 周）的大鼠可降低肌酸激酶 (CK) 和乳酸脱氢酶 (LDH) 的水平，并可防止结构改变和心脏功能障碍 [3]。在AMI大鼠模型中，福辛普利（4.67 mg/kg；口服；4周）可以抑制cleaved-caspase 3的产生和心肌细胞凋亡[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: po (oral gavage); 4 weeks
Experimental Results: Inhibition of cardiac dysfunction and structural changes and inhibition of apoptosis.

Absorption, Distribution and Excretion
Average absolute absorption is 36%. The primary site of absorption is the proximal small intestine (duodenum/jejunum). Food slows the rate of absorption with no effect on the extent of absorption.
After oral administration of radiolabeled fosinopril, approximately half of the absorbed dose is excreted in the urine and the remainder is excreted in the feces.
26 - 39 mL/min [healthy]

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Metabolism / Metabolites
Since fosinoprilat is not biotransformed after intravenous administration, fosinopril, not fosinoprilat, appears to be the precursor for the glucuronide and p-hydroxy metabolites.

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Biological Half-Life
12 hours

Hepatotoxicity
Fosinopril, like other ACE inhibitors, has been associated with a low rate of serum aminotransferase elevations (
Likelihood score: D (possible rare cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because no information is available on the use of fosinopril during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Fosinoprilat is ≥95% protein bound

[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 is a phosphinate ester-containing N-acyl derivative of (4S)-cyclohexyl-L-proline. It is used for the treatment of hypertension and heart failure. A pro-drug, it is hydrolysed in vivo to 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 is a phosphinic ester and a L-proline derivative. It is functionally related to a fosinoprilat. It is a conjugate acid of a fosinopril(1-).
Fosinopril is a phosphinic acid-containing ester prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is rapidly hydrolyzed to fosinoprilat, its principle active metabolite. Fosinoprilat inhibits ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Fosinopril may be used to treat mild to moderate hypertension, as an adjunct in the treatment of congestive heart failure, and to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy.
Fosinopril is an angiotensin-converting enzyme (ACE) inhibitor used in the therapy of hypertension and heart failure. Fosinopril is associated with a low rate of transient serum aminotransferase elevations during therapy and has been linked to rare instances of acute liver injury.
Fosinopril is a phosphinic acid-containing angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As an ester prodrug, fosinopril 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 in water outflow.
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 (annotation moved to).

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Drug Indication
For treating mild to moderate hypertension, use as an adjunct in treating congestive heart failure, and may be used to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy.
FDA Label

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Mechanism of Action
There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Fosinoprilat, the active metabolite of fosinopril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Fosinoprilat also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors.

C30H46NO7P

563.66254

563.301

98048-97-6

Fosinopril sodium;88889-14-9

55891

Typically exists as solid at room temperature

1.173 g/cm3

705.7ºC at 760 mmHg

149-153ºC

380.6ºC

1.531

6.059

120.02

1

7

15

39

850

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

BIDNLKIUORFRQP-KKDZQFHASA-N

InChI=1S/C30H46NO7P/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)/t25-,26+,30?,39?/m0/s1

(2R,4R)-4-cyclohexyl-1-(2-((2-methyl-1-(propionyloxy)propoxy)(4-phenylbutyl)phosphoryl)acetyl)pyrrolidine-2-carboxylic acid

SQ-28555SQ28555SQ 28555 FosinoprilMonopril

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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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;
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5、为保证最佳实验结果，工作液请现配现用！
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7、 以上所有助溶剂都可在 Invivochem.cn网站购买。