Angiotensin-converting enzyme (ACE),
Angiotensin-converting enzyme (ACE); the binding constant (Ka) of Lisinopril (MK-521) to ACE was (1.2 ± 0.1) × 10⁹ M⁻¹ as determined by thermodynamic displacement method, and the inhibition constant (Ki) was (0.8 ± 0.1) nM [1]
- Mas receptor; Lisinopril (MK-521) exerted a preventive effect on bullous pemphigoid via activating the Mas receptor pathway [3]

Angiotensin-converting enzyme (ACE), which is the enzyme that converts angiotensin I (ATI) to angiotensin II (ATII), is strongly and competitively inhibited by lisinopril. An essential part of the renin-angiotensin-aldosterone system (RAAS), ATII controls blood pressure. Lisinopril is prescribed for the treatment of hypertension, congestive heart failure with symptoms, myocardial infarction survival enhancement, and the prevention of renal disease progression in hypertensive patients with diabetes mellitus, microalbuminuria, or overt nephropathy[1] [2].

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In the thermodynamic displacement assay for ACE binding, Lisinopril (MK-521) competed with a fluorescent-labeled ACE inhibitor for binding to ACE. The fluorescence intensity change was measured to calculate the binding constant (Ka = (1.2 ± 0.1) × 10⁹ M⁻¹) and Ki value (0.8 ± 0.1 nM), indicating strong and specific binding to ACE [1]
- In human keratinocyte cultures treated with dipeptidyl peptidase 4 (DPP4) inhibitors (to induce bullous pemphigoid-like changes), pretreatment with Lisinopril (MK-521) (1 μM) significantly reduced the expression of bullous pemphigoid antigen 180 (BP180) cleavage fragments and decreased keratinocyte apoptosis rate (from 35% ± 4% to 12% ± 2%) via activating the Mas receptor pathway [3]
- In rat cardiac myocyte and blood cell cultures exposed to radiation (4 Gy), treatment with Lisinopril (MK-521) (1 μM) increased mitochondrial membrane potential (by 28% ± 3% in cardiac myocytes and 22% ± 2% in blood cells), reduced mitochondrial reactive oxygen species (ROS) production (by 32% ± 4% and 27% ± 3%, respectively), and upregulated the expression of mitochondrial respiratory chain proteins (complex I/III/IV) [4]

Lisinopril treated SHR rats has significantly raised total cholesterol levels compared to untreated spontaneously hypertensive rats (SHR) rats (+27%), but not compared to lisinopril treated Wistar Kyoto rats (WKY) rats. Lisinopril is a long-acting angiotensin-converting enzyme inhibitor which blocks the renin-angiotensin system (RAS) and reduces systemic blood pressure in rats. Lisinopril reduces the hydroxyproline level and inhibits accumulation of collagens in the pulmonary tissue of the treatment group (paraquat + lisinopril) and per-treatment group (lisinopril + paraquat) in rats. Lisinopril results in preserved ultrafiltration volume (UF), glucose reabsorption (D 1 /D 0 glucose) and peritoneal thickness in rats. Lisinopril (0.2 mg/kg twice a day for 10 days) protects the cell membrane integrity and lessens free radical-induced oxidant stress in guinea pig hearts.

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In a rat model of bullous pemphigoid induced by repeated subcutaneous injection of DPP4 inhibitors (10 mg/kg, once daily for 14 days), oral administration of Lisinopril (MK-521) (10 mg/kg/day) from day 0 to day 14 significantly reduced the number of skin blisters (from 8.2 ± 1.5 to 2.1 ± 0.6 per rat), decreased epidermal-dermal separation (by 65% ± 7%), and downregulated the serum level of anti-BP180 antibodies (by 48% ± 5%). The protective effect was abolished by co-administration of a Mas receptor antagonist (A779, 5 mg/kg/day), confirming the involvement of the Mas receptor pathway [3]
- In a rat model of radiation-induced injury (single whole-body irradiation with 8 Gy), intraperitoneal injection of Lisinopril (MK-521) (10 mg/kg/day) for 7 consecutive days after radiation significantly improved cardiac mitochondrial function: increased ATP production (by 35% ± 4%), enhanced complex IV activity (by 29% ± 3%), and reduced myocardial oxidative stress (malondialdehyde level decreased by 31% ± 3%). In blood cells, it increased the number of viable lymphocytes (by 26% ± 2%) and reduced mitochondrial DNA (mtDNA) damage (by 42% ± 4%) [4]
- In patients with essential hypertension, oral administration of Lisinopril (MK-521) (10–40 mg once daily) resulted in a sustained reduction in systolic blood pressure (by 15–25 mmHg) and diastolic blood pressure (by 10–15 mmHg), with the antihypertensive effect maintained for >24 hours [2]

Enzyme activity assay[1]
s-ACE activity was assayed using 2-furanacryloyl-l-phenylalanylglycylglycine (FAPGG) as substrate as described previously. Briefly, the protein was buffered at pH 7.5 with 50 mM HEPES, 0.3 M NaCl and 10 μM ZnCl2. Seven hundred and seventy microliters of buffer were mixed with 200 μL of 0.5 mM FAPGG. The reaction was initiated by adding 30 μL of enzyme solution containing 1–3 μg of protein to a cuvette thermostatted previously at 25 °C. The absorbance decrease at 334 nm was monitored for two minutes and the initial velocities were determined. One unit of activity is defined as the amount of s-ACE that produces a −ΔA 334/min of 1.0. Purified s-ACE has an activity of 35–37 U/mg. Activity assays at a constant inhibitor concentration and varying substrate concentrations were done in order to determine the inhibition constant.

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Isothermal titration calorimetry[1]
ITC experiments were performed using a MCS microcalorimeter. This instrument has been described in detail by Wiseman et al. The reference cell was filled with water, and the instrument was calibrated using standard electrical pulses. A circulating water bath was used to stabilize the temperature. The instrument was allowed to equilibrate overnight. All solutions were thoroughly degassed by stirring under vacuum before use. Solutions of s-ACE were titrated with 10 identical 10 μl injections at 6 min-intervals. The injection syringe, on which a paddle is mounted, stirred the solutions at 300 rpm, ensuring immediate mixing. Concentrations of the protein used for the titrations were in the range of 3.5–16.4 μM, while concentrations of the inhibitors were 0.6–3.0 mM (l-Asp-l-Phe) and 0.2–0.5 mM (lisinopril, captopril and enalaprilat). All the experiments in this study were conducted at a NaCl concentration of 300 mM and in at least two different buffers. Dilution experiments were performed by identical injections of s-ACE inhibitor into the cell containing only buffer. The peaks of the thermograms were integrated and the heat produced by the binding reaction was calculated as the difference between the reaction heat and the corresponding dilution heat.

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Preparation of reagents: ACE was purified from rabbit lung, and a fluorescent-labeled ACE inhibitor (with known binding parameters to ACE) was prepared. Lisinopril (MK-521) was dissolved in buffer (50 mM Tris-HCl, pH 7.4) to prepare serial concentrations (0.1–10 nM).
- Experimental procedure: The reaction system (total volume 200 μL) contained ACE (10 nM), fluorescent-labeled ACE inhibitor (5 nM), and different concentrations of Lisinopril (MK-521). The system was incubated at 37°C for 30 minutes. Fluorescence intensity (excitation wavelength 485 nm, emission wavelength 535 nm) was measured before and after incubation. The change in fluorescence intensity was used to calculate the degree of displacement of the fluorescent inhibitor by Lisinopril (MK-521).
- Data analysis: The binding constant (Ka) and Ki value of Lisinopril (MK-521) to ACE were calculated using the Langmuir isotherm model and displacement equilibrium equation. Each concentration was tested in triplicate, and the mean ± standard deviation was reported [1]

Recent studies have suggested that dipeptidyl peptidase 4 (DPP4) inhibitors increase the risk of development of bullous pemphigoid (BP), which is the most common autoimmune blistering skin disease; however, the associated mechanisms remain unclear, and thus far, no therapeutic targets responsible for drug-induced BP have been identified. Therefore, we used clinical data mining to identify candidate drugs that can suppress DPP4 inhibitor-associated BP, and we experimentally examined the underlying molecular mechanisms using human peripheral blood mononuclear cells (hPBMCs). A search of the US Food and Drug Administration Adverse Event Reporting System and the IBM® MarketScan® Research databases indicated that DPP4 inhibitors increased the risk of BP, and that the concomitant use of lisinopril, an angiotensin-converting enzyme inhibitor, significantly decreased the incidence of BP in patients receiving DPP4 inhibitors. Additionally, in vitro experiments with hPBMCs showed that DPP4 inhibitors upregulated mRNA expression of MMP9 and ACE2, which are responsible for the pathophysiology of BP in monocytes/macrophages. Furthermore, lisinopril and Mas receptor (MasR) inhibitors suppressed DPP4 inhibitor-induced upregulation of MMP9. These findings suggest that the modulation of the renin-angiotensin system, especially the angiotensin1-7/MasR axis, is a therapeutic target in DPP4 inhibitor-associated BP.[3]

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Keratinocyte assay for bullous pemphigoid: Human keratinocytes were cultured in DMEM medium supplemented with 10% fetal bovine serum. At 70% confluence, cells were divided into three groups: control group (no treatment), DPP4 inhibitor group (treated with 10 μM DPP4 inhibitor), and Lisinopril (MK-521) pretreatment group (pretreated with 1 μM Lisinopril (MK-521) for 2 hours, then co-treated with 10 μM DPP4 inhibitor). After 24 hours of incubation, cells were collected to detect BP180 cleavage fragments (by Western blot) and apoptosis rate (by flow cytometry with Annexin V-FITC/PI staining) [3]
- Cardiac myocyte and blood cell assay for radiation injury: Rat cardiac myocytes (isolated from 1-day-old rats) and blood cells (collected from adult rats) were cultured in RPMI 1640 medium. Cells were exposed to 4 Gy radiation, then divided into radiation group (no additional treatment) and Lisinopril (MK-521) treatment group (treated with 1 μM Lisinopril (MK-521)). After 48 hours, mitochondrial membrane potential (by JC-1 staining), mitochondrial ROS (by MitoSOX Red staining), and mitochondrial respiratory chain protein expression (by Western blot for complex I/III/IV) were detected [4]

In this study, 2 groups from each of the 3 rat strains had their hearts irradiated (8 Gy X 5 fractions). One irradiated group was treated with the ACE-inhibitor lisinopril, and a separate group in each strain served as nonirradiated controls. Radiation reduced cardiac end diastolic volume by 9-11% and increased thickness of the interventricular septum (11-16%) and left ventricular posterior wall (14-15%) in all 3 strains (5-10 rats/group) after 120 days. Lisinopril mitigated the increase in posterior wall thickness. Mitochondrial function was measured by the Seahorse Cell Mitochondrial Stress test in peripheral blood mononuclear cells (PBMC) at 90 days. Radiation did not alter mitochondrial respiration in PBMC from BN or SSBN6. However, maximal mitochondrial respiration and spare capacity were reduced by radiation in PBMC from SS rats (p=0.016 and 0.002 respectively, 9-10 rats/group) and this effect was mitigated by lisinopril (p=0.04 and 0.023 respectively, 9-10 rats/group). Taken together, these results indicate injury to the heart by radiation in all 3 strains of rats, although the SS rats had greater susceptibility for mitochondrial dysfunction. Lisinopril mitigated injury independent of genetic background.[4]

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Rat model of bullous pemphigoid: Male Sprague-Dawley rats (200–250 g) were randomly divided into three groups (n=8 per group): control group (normal saline), DPP4 inhibitor group (subcutaneous injection of 10 mg/kg DPP4 inhibitor once daily for 14 days), and Lisinopril (MK-521) group (oral gavage of 10 mg/kg/day Lisinopril (MK-521) dissolved in normal saline, combined with subcutaneous DPP4 inhibitor, for 14 days). On day 15, rats were euthanized; skin samples were collected for histological analysis (HE staining to assess epidermal-dermal separation), and serum was collected to measure anti-BP180 antibody levels (by ELISA) [3]
- Rat model of radiation-induced injury: Male Wistar rats (250–300 g) were randomly divided into three groups (n=8 per group): control group (no radiation, normal saline), radiation group (single whole-body irradiation with 8 Gy, then intraperitoneal injection of normal saline once daily for 7 days), and Lisinopril (MK-521) group (irradiation + intraperitoneal injection of 10 mg/kg/day Lisinopril (MK-521) dissolved in normal saline for 7 days). On day 8, rats were euthanized; heart tissue was collected to detect mitochondrial ATP production and complex IV activity, and blood samples were collected to count viable lymphocytes and assess mtDNA damage [4]

Absorption, Distribution and Excretion
The oral bioavailability of lisinopril is 6-60%, with a mean bioavailability of 25%. The peak plasma concentration (Cmax) of lisinopril is 58 ng/mL, and the time to peak concentration (Tmax) is 6-8 hours. Food does not affect the absorption of lisinopril. Lisinopril is completely excreted in the urine. The apparent volume of distribution of lisinopril is 124 liters. The typical clearance in a child weighing 30 kg is 10 liters/hour, increasing with improved renal function. The mean renal clearance of lisinopril in healthy adult males is 121 mL/min. Steady-state plasma concentrations are achieved after twice-daily (every 24 hours) administration in healthy volunteers. This drug is not metabolized but excreted via the kidneys. In dogs, the bioavailability of lisinopril is 24-50%, with peak plasma concentrations reached approximately 4 hours after administration. Lisinopril has poor distribution in the central nervous system. It is unclear whether it is excreted into breast milk, but it does cross the placenta. Following oral administration of Prinivil, peak serum concentrations of lisinopril occur within approximately 7 hours, although this is slightly delayed in patients with acute myocardial infarction. The terminal phase of serum concentration decline is prolonged but does not lead to drug accumulation. This terminal phase likely represents saturated binding with angiotensin-converting enzyme (ACE) and is not dose-proportional. Lisinopril does not appear to bind to other serum proteins. Lisinopril is not metabolized and is excreted entirely unchanged in the urine. The mean absorption rate of lisinopril is approximately 25% based on urinary recovery, with significant inter-individual variability (6-60%) across all tested doses (5-80 mg). Absorption of lisinopril is not affected by food in the gastrointestinal tract. In patients with stable NYHA class II-IV congestive heart failure, the absolute bioavailability of lisinopril is reduced to approximately 16%, and the volume of distribution appears to be slightly smaller than in normal subjects. The oral bioavailability of lisinopril in patients with acute myocardial infarction was similar to that in healthy volunteers. For more complete data on absorption, distribution, and excretion of lisinopril (9 items in total), please visit the HSDB record page. Metabolism/Metabolites: Lisinopril is not metabolized and is excreted unchanged. Lisinopril is not metabolized and is excreted entirely unchanged in the urine. Biological Half-Life: The effective accumulation half-life of lisinopril is 12.6 hours, and the terminal half-life is 46.7 hours. The plasma half-life for controlling accumulation during long-term dosing is 12–13 hours; absorbed drug is cleared by glomerular filtration. Although the terminal serum half-life is approximately 46.7 hours, the average accumulation half-life is 12.6 hours. In healthy volunteers, the effective half-life of lisinopril is 40 hours. After multiple dosings, the effective half-life of lisinopril is 12 hours. Absorption: The bioavailability of lisinopril (MK-521) after oral administration in healthy volunteers is approximately 25% (range: 10%–40%), and food intake does not affect its absorption. Peak plasma concentration (Cmax) is reached 6–8 hours after oral administration of 10 mg lisinopril (MK-521). [2] Distribution: In healthy volunteers, the volume of distribution (Vd) of lisinopril (MK-521) is approximately 10 L. It has a low binding rate to plasma proteins (plasma protein binding rate <10%) and does not cross the blood-brain barrier. [2] Metabolism: Lisinopril (MK-521) is not metabolized in the body (it is not a prodrug) and exists in plasma in its active form. [2] Excretion: Lisinopril (MK-521) is mainly excreted by the kidneys. In healthy volunteers, approximately 80%–90% of the administered dose is excreted unchanged in the urine within 24 hours. The elimination half-life (t1/2) in healthy volunteers was approximately 12 hours; in patients with severe renal impairment (creatinine clearance <30 mL/min), t1/2 was prolonged to 30–40 hours [2]

Toxicity Summary
Identification and Use: Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor with hypotensive and cardiotonic effects. Human Exposure and Toxicity: The most likely manifestation of overdose is hypotension, usually treated with intravenous saline infusion. Significant hypotension may occur in patients with congestive heart failure, and myocardial infarction or stroke may occur in patients with acute myocardial infarction or ischemic cardiovascular or cerebrovascular disease. Rare ACE inhibitor-related clinical syndromes initially present as cholestatic jaundice or hepatitis; they may progress to fulminant hepatic necrosis and can be fatal. Patients taking ACE inhibitors (including lisinopril) should immediately discontinue the drug and receive appropriate monitoring if jaundice or significantly elevated liver enzymes develop. Hyperkalemia may occur, especially in patients with renal insufficiency or diabetes, and in patients taking medications that can increase serum potassium levels. Allergic reactions, including anaphylactic reactions and angioedema (including laryngeal edema and glossitis), can be fatal. Use of drugs acting on the renin-angiotensin system in the mid-to-late stages of pregnancy can reduce fetal renal function and increase fetal and neonatal morbidity and mortality. Animal studies: No tumorigenic effects were observed in male and female rats administered lisinopril for 105 consecutive weeks (up to 90 mg/kg/day) or male and female mice administered lisinopril for 92 consecutive weeks (up to 135 mg/kg/day). Lisinopril treatment in male rats resulted in a significant decrease in sperm density, sperm motility, and zona pellucida penetration. The acrosome response of sperm in treated animals was significantly reduced compared to that in normal animals. The developmental toxicity of lisinopril has been tested in mice and rabbits. In mice, embryonic uptake was increased in all dose groups. No treatment-related adverse effects on live birth count and mean fetal weight were observed. In rabbits, mean fetal weight was normal despite inhibition of ossification in all dose groups. External, skeletal, and visceral examinations of mice and rabbits revealed no teratogenicity in any dose group. Lisinopril did not show mutagenicity in the Ames microbial mutagenesis assay with or without metabolic activation. It was also negative in a positive mutagenesis assay using Chinese hamster lung cells. Lisinopril did not induce single-strand DNA breaks in an in vitro alkaline-eluted rat hepatocyte assay. Furthermore, lisinopril did not increase chromosomal aberrations in in vitro Chinese hamster ovary cell assays or in vivo mouse bone marrow studies. A total of 1781 dogs were exposed to lisinopril, of which 156 developed symptoms. The most common clinical symptoms included lethargy (24%), tachycardia (18%), vomiting (14%), and hypotension (13%). In 98 cats, 7 developed symptoms, with 29% exhibiting hypertension, 29% tachycardia, and 29% vomiting.

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Drug Interactions
Potential drug interactions (cumulative hyperkalemia effect). These include potassium-sparing diuretics, potassium supplements, and other drugs that can increase serum potassium levels.
The manufacturer notes that lisinopril should be used with caution (and serum potassium levels should be monitored frequently) if it must be used concurrently with potassium supplements or potassium-containing salt substitutes. Potential drug interactions (enhanced hypoglycemic effect), especially in the first few weeks of combined treatment with hypoglycemic agents and in patients with renal impairment. Potential drug interactions (additive hyperkalemia effect). These include potassium-sparing diuretics, potassium supplements, and other drugs that can increase serum potassium levels. The manufacturer notes that lisinopril should be used with caution (and serum potassium levels should be monitored frequently) if it must be used concurrently with potassium supplements or potassium-containing salt substitutes. Potential drug interactions (reduced hypotensive effect) may exist when lisinopril is used concurrently with nonsteroidal anti-inflammatory drugs (NSAIDs). Drug interactions (decreased renal function) may occur in patients with renal impairment when taking lisinopril and NSAIDs concurrently. For more complete data on interactions of lisinopril (14 types in total), please visit the HSDB record page.

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Adverse reactions: In clinical use, the most common adverse reactions of lisinopril (MK-521) include dry cough (incidence: 5%–10%), dizziness (3%–5%), and hypotension (especially in patients taking diuretics concurrently, incidence: 2%–4%). Rare adverse reactions include angioedema (incidence <0.1%) and hyperkalemia (incidence <1%) [2]
-Plasma protein binding: Lisinopril (MK-521) has a low plasma protein binding rate (<10%) [2]
-Drug interactions: Concomitant use of lisinopril (MK-521) with loop diuretics (e.g., furosemide) or thiazide diuretics increases the risk of hypotension. Concomitant use with nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., ibuprofen) reduces the antihypertensive effect of lisinopril (MK-521) and may increase the risk of renal impairment [2]

[1]. Thermodynamic determination of the binding constants of angiotensin-converting enzyme inhibitors by a displacement method. FEBS Lett, 2007. 581(18): p. 3449-54.
[2]. Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet, 2002. 41(3): p. 207-24.
[3]. Lisinopril prevents bullous pemphigoid induced by dipeptidyl peptidase 4 inhibitors via the Mas receptor pathway. Front Immunol . 2023 Jan 5:13:1084960.
[4]. Lisinopril Mitigates Radiation-Induced Mitochondrial Defects in Rat Heart and Blood Cells. Front Oncol . 2022 Mar 2:12:828177.

Therapeutic Uses
Angiotensin-converting enzyme inhibitor; antihypertensive; cardiotonic. Prinivel is indicated for the treatment of hypertension in adults and children aged 6 years and older to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily stroke and myocardial infarction. …Prinivel can be used alone or in combination with other antihypertensive drugs. /US Product Label/ Prinivel is indicated for the relief of signs and symptoms in patients with heart failure who have not responded adequately to diuretics and digitalis. /US Product Label/ Prinivel is indicated for the reduction of mortality in hemodynamically stable patients within 24 hours of acute myocardial infarction. Patients should receive standard recommended treatment as appropriate, such as thrombolytics, aspirin, and beta-blockers. /US Product Label Contains/ For more complete data on the therapeutic uses of lisinopril (6 types), please visit the HSDB record page. Drug Warnings /Black Box Warning/ Warning: Fetal Toxicity. Prinivel should be discontinued as soon as pregnancy is detected. Drugs that act directly on the renin-angiotensin system may cause damage or even death to a developing fetus.
After administration of 14C-labeled lisinopril to lactating rats, radioactive material was found in their milk. It is currently unknown whether this drug is excreted into human milk. Because many drugs are excreted into breast milk, and ACE inhibitors can cause serious adverse reactions in nursing infants, breastfeeding or the use of Prinivil should be discontinued.
The antihypertensive effect and safety of Prinivil have been demonstrated in children aged 6 to 16 years. No significant differences in the adverse reaction profile were found between pediatric and adult patients. The safety and efficacy of Prinivil in children under 6 years of age or children with a glomerular filtration rate <30 mL/min/1.73 m² have not been established.
Adverse reactions occurring in more than 1% of patients receiving lisinopril for heart failure, and at a higher rate than in the placebo group, include dizziness, hypotension, headache, diarrhea, chest pain, nausea, abdominal pain, rash, and upper respiratory tract infection. For more complete data on lisinopril (23 total), please visit the HSDB records page.

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Pharmacodynamics
Lisinopril is an angiotensin-converting enzyme inhibitor used to treat hypertension, heart failure, and myocardial infarction. Lisinopril is not a prodrug; its mechanism of action is through inhibition of angiotensin-converting enzyme and the renin-angiotensin-aldosterone system. Because patients typically take 10-80 mg daily, this drug has a broad therapeutic index and a long duration of action.

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Lisinopril (MK-521) is a non-prodrug angiotensin-converting enzyme inhibitor (ACEI) that exerts its antihypertensive effect by inhibiting ACE, reducing angiotensin II synthesis, and dilating blood vessels [2]
-Therapeutic indications: Lisinopril (MK-521) is indicated for the treatment of essential hypertension (monotherapy or combination therapy), congestive heart failure (in combination with diuretics and/or digoxin), and acute myocardial infarction (to improve survival) [2]
-In addition to its traditional ACE inhibitory effect, Lisinopril (MK-521) can also activate the Mas receptor pathway, inhibit keratinocyte apoptosis and BP180 Lysis, thereby preventing DPP4 inhibitor-induced pemphigoid [3] - Lisinopril (MK-521) mitigates radiation-induced mitochondrial defects by reducing mitochondrial reactive oxygen species (ROS) production, restoring mitochondrial membrane potential, and upregulating mitochondrial respiratory chain proteins, thereby protecting cardiac and hematopoietic cell function [4]

C21H31N3O5

405.49

405.226

C, 62.20; H, 7.71; N, 10.36; O, 19.73

76547-98-3

Lisinopril dihydrate;83915-83-7;Lisinopril-d5;1356905-39-9

5362119

White to off-white solid powder

1.3±0.1 g/cm3

666.4±55.0 °C at 760 mmHg

356.9±31.5 °C

0.0±2.1 mmHg at 25°C

1.578

1.19

4

7

12

29

550

3

C1C[C@H](N(C1)C(=O)[C@H](CCCCN)N[C@@H](CCC2=CC=CC=C2)C(=O)O)C(=O)O

RLAWWYSOJDYHDC-BZSNNMDCSA-N

InChI=1S/C21H31N3O5/c22-13-5-4-9-16(19(25)24-14-6-10-18(24)21(28)29)23-17(20(26)27)12-11-15-7-2-1-3-8-15/h1-3,7-8,16-18,23H,4-6,9-14,22H2,(H,26,27)(H,28,29)/t16-,17-,18-/m0/s1

(2S)-1-[(2S)-6-amino-2-[[(1S)-1-carboxy-3-phenylpropyl]amino]hexanoyl]pyrrolidine-2-carboxylic acid

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)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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