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

Co-sedimentation of liposomes and recombinant LPLA2 is partially inhibited by fosinopril (0, 1, 10, 33, 100 μM; 30 min) [1]. The soluble esterase activity of LPLA2 is not inhibited by fosinopril (250 nM) [1]. With a Ki value of 1.675 μM, fosinopril (0.372, 0.744, 1.116 μM) inhibits ACE activity in a non-competitive manner [2].

By decreasing the levels of lactate dehydrogenase (LDH) and creatine kinase (CK), fosinopril (oral; 4.67 mg/kg; 4 weeks) counteracts cardiac dysfunction and structural alterations [3]. In rat models of acute myocardial infarction, fosinopril (oral; 4.67 mg/kg; 4 weeks) reduces the expression of cleaved-caspase 3 and cardiomyocyte apoptosis.

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In patients with New York Heart Association (NYHA) class II–III heart failure, oral administration of Fosinopril Sodium (SQ28555) (10 mg once daily) for 12 weeks significantly improved hemodynamic parameters:
1. Systolic blood pressure (SBP) decreased from 135 ± 12 mmHg (baseline) to 118 ± 10 mmHg, and diastolic blood pressure (DBP) decreased from 82 ± 8 mmHg to 72 ± 6 mmHg.
2. Pulmonary capillary wedge pressure (PCWP) reduced from 22 ± 4 mmHg to 15 ± 3 mmHg (a marker of left ventricular filling pressure).
3. Cardiac output (CO) increased from 3.2 ± 0.5 L/min to 4.1 ± 0.6 L/min, and stroke volume (SV) increased from 45 ± 6 mL/beat to 58 ± 5 mL/beat.
4. Systemic vascular resistance (SVR) decreased by 28% ± 4% (from 1850 ± 200 dyn·s/cm⁵ to 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 bioavailability of fosinopril sodium (SQ28555) (a prodrug) in healthy volunteers was approximately 36%, with no significant effect from food intake (AUC and Cmax changes <10%). Peak plasma concentrations of its active metabolite, fosinopril, were reached 3 hours after oral administration [2]. Distribution: The volume of distribution (Vd) of fosinopril (the active metabolite) in healthy volunteers was approximately 13 liters. Fosinopril sodium (SQ28555) and fosinopril cannot cross the blood-brain barrier [2]. Metabolism: Fosinopril sodium (SQ28555) is rapidly metabolized by esterases in the liver and gastrointestinal tract to produce its active metabolite, fosinopril (the main form that exerts ACE inhibitory activity). No other active metabolites were detected [2]. Excretion: In healthy volunteers, fosinopril was mainly excreted via the kidneys and bile (50% each). This dual excretion pathway reduces the risk of drug accumulation in patients with single-organ (kidney or liver) dysfunction. The elimination half-life (t1/2) of fosinoprila is approximately 11.5 hours [2]

Plasma protein binding: The plasma protein binding of fosinopril (the active metabolite) is approximately 95% [2]
- Adverse reactions: In clinical use, the most common adverse reactions of fosinopril sodium (SQ28555) include dry cough (incidence: 4%–7%), dizziness (2%–3%), and fatigue (1%–2%). Rare adverse reactions include angioedema (incidence <0.1%) and hyperkalemia (more common in patients with renal insufficiency or those taking potassium supplements) [2]
- Drug interactions: Concomitant use with loop diuretics (e.g., furosemide) increases the risk of hypotension. Concomitant use with nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., ibuprofen) may reduce the hypotensive 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, used to treat hypertension and heart failure. It is a prodrug whose phosphonate group is hydrolyzed in vivo to produce the corresponding phosphonic acid—fosinoprilat, which is its active metabolite. Fosinopril sodium has multiple functions, including as an EC 3.4.15.1 (peptidyl dipeptidase A) inhibitor, a prodrug, and an antihypertensive agent. It contains a fosinopril (1-) domain. Fosinopril sodium is the sodium salt of fosinopril, a phosphonic acid-containing angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Fosinopril sodium is an ester prodrug that is hydrolyzed by esterases to produce its active metabolite, fosinoprilat. Fosinoprilat specifically and competitively inhibits angiotensin-converting enzyme, thereby reducing the production of the potent vasoconstrictor angiotensin II, leading to decreased vasopressor activity. In addition, it can reduce adrenocortical angiotensin II-mediated aldosterone secretion, thereby reducing sodium retention and increasing serum potassium levels. (NCI05)
A phosphonate-containing angiotensin-converting enzyme inhibitor that is effective in treating hypertension. It is a prodrug that can be converted into its active metabolite, fosinoprilat.
See also: fosinopril (containing the active portion); fosinoprilat (containing the active portion); fosinopril sodium; hydrochlorothiazide (component).
1. Fosinopril sodium (SQ28555) is an angiotensin-converting enzyme inhibitor (ACEI) prodrug with a unique phosphonate structure. Unlike other ACEIs (such as captopril and enalapril), fosinopril sodium contains a phosphonate group rather than a thiol or carboxylic acid group, which gives it dual renal and biliary excretion properties[1][2]. 2. Its pharmacological mechanism is to inhibit ACE, reduce the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor), thereby dilating blood vessels throughout the body and lungs, and improving cardiac hemodynamics in patients with 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 (in combination with diuretics and/or digoxin) [2]. 4. No dose adjustment is required for patients with renal insufficiency (creatinine clearance 10–40 mL/min) or hepatic insufficiency. Fosinopril sodium (SQ28555) is an essential drug due to its dual excretion route, which is superior to ACEIs that are excreted only by 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

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

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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)

Solubility in Formulation 1: 9.09 mg/mL (15.52 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)