Angiotensin-converting enzyme (ACE) [1]

In vitro activity: Enalapril is rapidly converted by ester hydrolysis to enalaprilat, a potent ACE inhibitor; Enalapril itself is only a weak ACE inhibitor. Enalapril lowers peripheral vascular resistance without causing an increase in heart rate.

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In a mouse model of endothelial dysfunction induced by a high-methionine diet (2% methionine in feed for 8 weeks), oral administration of Enalapril Maleate (MK-421) (10 mg/kg/day) for 8 weeks significantly improved endothelial function. Specifically:
1. Acetylcholine-induced endothelium-dependent vasodilation of aortic rings increased from 32% ± 4% (model group) to 68% ± 5% (Enalapril group), as measured by a myograph system.
2. Plasma nitric oxide (NO) levels increased by 45% ± 6% compared to the model group, while plasma malondialdehyde (MDA, a marker of oxidative stress) levels decreased by 38% ± 5%.
3. Western blot analysis showed that the expression of endothelial nitric oxide synthase (eNOS) in aortic tissue was upregulated by 52% ± 7% compared to the model group, and the expression of NADPH oxidase subunit p47phox (a key factor in oxidative stress) was downregulated by 41% ± 6% [1]

MK-421, also known as enalapril, is a prodrug that is a member of the ACE inhibitor class of medicines. After oral administration, it is quickly converted by the liver to enalaprilat. ACE, the enzyme that converts angiotensin I (ATI) to angiotensin II (ATII), is strongly and competitively inhibited by enalapril (MK-421). Crucial to the renin-angiotensin-aldosterone system (RAAS) is ATII, which controls blood pressure. Clinical conditions that can be treated with enalapril include symptomatic congestive heart failure and essential or renovascular hypertension[1].

oral
Rats

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Animal model establishment: Male C57BL/6 mice (8–10 weeks old, 20–25 g) were randomly divided into three groups (n=8 per group):
- Control group: Fed a standard diet (0.3% methionine) and given normal saline by oral gavage.
- High-methionine model group: Fed a high-methionine diet (2% methionine) and given normal saline by oral gavage.
- Enalapril Maleate (MK-421) treatment group: Fed a high-methionine diet (2% methionine) and given Enalapril Maleate (MK-421) dissolved in normal saline (10 mg/kg/day) by oral gavage.
- Treatment duration: All groups were treated continuously for 8 weeks, with food and water provided ad libitum.
- Sample collection and detection: After 8 weeks, mice were euthanized by cervical dislocation. The thoracic aorta was quickly isolated and used for:
1. Vascular ring experiment (to measure endothelium-dependent vasodilation using a myograph).
2. Western blot analysis (to detect eNOS and p47phox protein expression).
Plasma was collected to measure NO and MDA levels using biochemical assay kits [1]

Absorption, Distribution and Excretion
Following oral administration, peak plasma concentration (Cmax) of enalapril is reached within 1 hour of administration, while that of enalapril is reached 3 to 4 hours after administration. Steady-state plasma concentrations are achieved with a fourth daily dose, and repeated dosing does not lead to drug accumulation. However, patients with creatinine clearance below 30 mL/min may experience enalapril accumulation. Food intake has been reported to have little effect on drug absorption. Approximately 60% of enalapril is absorbed after oral administration. The mean bioavailability of enalapril is approximately 40% compared to intravenous enalapril. Enalapril is primarily excreted via the kidneys, with approximately 94% of the total dose excreted in urine or feces as enalapril or unchanged drug. Approximately 61% and 33% of the total dose are recovered in urine and feces, respectively. In urine, approximately 40% of the recovered dose is enalapril. The volume of distribution of enalapril has not been determined. Enalapril can penetrate most tissues, especially the kidneys and blood vessels, but its ability to cross the blood-brain barrier at therapeutic doses has not been confirmed. In canine studies, enalapril and enalapril-ladenine have poor ability to cross the blood-brain barrier. Very little of the drug enters milk, but it is significantly transported via the fetal route. The drug can cross the placental barrier in rats and hamsters. Renal clearance in healthy male volunteers after oral administration is approximately 158 ± 47 mL/min. It has been reported that enalapril and enalapril-ladenine are undetectable in plasma 4 hours after administration. This study analyzed the pharmacokinetics and pharmacodynamics of enalapril administered intravenously at 0.50 mg/kg, orally as a placebo, and orally at three different doses (0.50, 1.00, and 2.00 mg/kg) in seven healthy horses. Serum concentrations of enalapril and enalapril-ladenine were measured for pharmacokinetic analysis. Pharmacodynamic analysis was performed by measuring angiotensin-converting enzyme (ACE) activity, serum blood urea nitrogen (SUN), creatinine, and electrolyte levels, and monitoring blood pressure. Following intravenous administration of enalapril, the elimination half-lives of enalapril and enalaprilat were 0.67 hours and 2.76 hours, respectively. After oral administration of enalapril, all horses had enalapril concentrations below the limit of quantitation (10 ng/mL), and 4 out of 7 horses had enalaprilat concentrations below the limit of quantitation. The mean angiotensin-converting enzyme (ACE) inhibition rates after intravenous administration of 0.50 mg/kg enalapril, placebo, and oral administration of 0.50, 1.00, and 2.00 mg/kg enalapril were 88.38%, 3.24%, 21.69%, 26.11%, and 30.19%, respectively. Blood pressure, SUN, creatinine, and electrolyte levels remained constant throughout the experiment. Unlike enalapril, enalapril maleate is well absorbed after oral administration. Although enalapril is a more potent angiotensin-converting enzyme inhibitor than enalapril, its high polarity results in low gastrointestinal absorption, with only about 3-12% of the oral dose being absorbed. In healthy individuals and hypertensive patients, approximately 55-75% of the oral dose of enalapril maleate is rapidly absorbed by the gastrointestinal tract. Food does not appear to significantly affect the rate or extent of enalapril maleate absorption. After oral administration, enalapril maleate undergoes first-pass metabolism primarily in the liver, hydrolyzing into enalapril. Following a single oral dose of enalapril maleate, its antihypertensive effect typically appears within 1 hour and peaks within 4-8 hours. The antihypertensive effect at commonly used doses usually lasts 12-24 hours, but in some patients, the effect may diminish at the end of the dosing interval. Blood pressure reduction may be a gradual process, requiring several weeks of treatment to achieve full efficacy.
After intravenous injection of enalapril, the antihypertensive effect is usually observed within 5-15 minutes and reaches its maximum effect within 1-4 hours; the duration of the antihypertensive effect appears to be dose-related, but at the recommended dose, the duration of the antihypertensive effect is approximately 6 hours in most patients. Inhibition of plasma angiotensin-converting enzyme (ACE) and a decrease in blood pressure appear to be associated with plasma enalapril concentrations reaching 10 ng/mL, which achieves maximum blocking effect on plasma ACE. Blood pressure gradually returns to pre-treatment levels after discontinuation of enalapril or enalapril; to date, there have been no reports of rebound hypertension following abrupt discontinuation. Enalapril/
For more complete data on the absorption, distribution, and excretion of enalapril (11 in total), please visit the HSDB records page.

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Metabolism/Metabolites
Approximately 60% of the absorbed dose is extensively hydrolyzed to enalapril via hepatic esterase-mediated deesterification. No further metabolism after bioactivation to enalapril has been observed in humans. Approximately 60% of the absorbed dose of enalapril is extensively hydrolyzed to enalaprilat primarily in the liver by esterases. About 20% appears to be hydrolyzed during the first pass through the liver; this hydrolysis does not appear to occur in human plasma. Enalaprilat is a more potent angiotensin-converting enzyme inhibitor than enalapril. There is no evidence of other metabolites of enalapril in humans, rats, or dogs. However, the depropanol metabolite of enalaprilat has been detected in the urine of rhesus monkeys, representing 13% of the oral dose of enalapril maleate. In patients with severe hepatic impairment, the hydrolysis of enalapril to enalaprilat may be delayed and/or impaired, but the pharmacodynamic effects of the drug do not appear to be significantly altered.

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Biological Half-Life
The mean terminal half-life of enalaprilat is 35–38 hours. The effective half-life after multiple doses is 11–14 hours. The prolonged terminal half-life is due to the binding of enalapril to angiotensin-converting enzyme (ACE). After oral administration, the half-life of unmetabolized enalapril appears to be less than 2 hours in healthy individuals and patients with normal hepatic and renal function, but it may be prolonged in patients with congestive heart failure. In patients with congestive heart failure, the half-lives of enalapril after a single oral dose of 5 or 10 mg of enalapril maleate are 3.4 hours and 5.8 hours, respectively. The elimination of enalapril may also be prolonged in patients with congestive heart failure or impaired hepatic function compared to healthy individuals and hypertensive patients. Long-term observation of serum enalapril concentrations after oral or intravenous administration suggests that the mean terminal half-life of enalapril is approximately 35–38 hours (range: 30–87 hours). …It has been reported that in healthy individuals with normal renal function, the mean effective accumulation half-life of enalapril (measured based on urinary recovery) is approximately 11 hours.

Toxicity Summary
Identification and Uses: Enalapril is an angiotensin-converting enzyme inhibitor and an antihypertensive drug. Human Studies: Enalapril overdose primarily produces a prolongation of its pharmacological action as an angiotensin-converting enzyme inhibitor. In two patients, plasma angiotensin-converting enzyme activity was completely inhibited within 10–15 hours following acute ingestion of 300–440 mg enalapril maleate. The most likely manifestation of enalapril overdose is hypotension, which can be severe and may be accompanied by drowsiness. The onset and duration of hypotension may be prolonged after acute overdose. Renal dysfunction, including acute renal failure, hyperkalemia, and hyponatremia, may also occur. Use of drugs acting on the renin-angiotensin system in the second and third trimesters of pregnancy can reduce fetal renal function and increase fetal and neonatal morbidity and mortality. The resulting oligohydramnios may be associated with fetal lung hypoplasia and skeletal malformations. Potential neonatal adverse reactions include craniosynostosis, anuria, hypotension, renal failure, and death. Once pregnancy is confirmed, enalapril maleate tablets should be discontinued as soon as possible. Animal studies: No tumorigenic effects were observed in male and female rats administered enalapril for 106 consecutive weeks (up to 90 mg/kg/day) or male and female mice administered enalapril for 94 consecutive weeks (up to 90 and 180 mg/kg/day, respectively). In male and female rats, treatment with enalapril at daily doses up to 90 mg/kg did not adversely affect reproductive function. Enalapril maleate and its active diacid were not mutagenic in the Ames microbial mutagen assay, with or without metabolic activation. Enalapril also showed negative results in the following genotoxicity studies: rec-assay, E. coli reverse mutation assay, sister chromatid exchange assay in cultured mammalian cells, mouse micronucleus assay, and in vivo cytogenetics studies using mouse bone marrow.

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Hepatotoxicity
As with other ACE inhibitors, enalapril is associated with a low incidence of elevated serum transaminases (
Probability score: B (probably but rarely causes clinically significant liver injury)).

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Effects during pregnancy and lactation
◉ Overview of use during lactation
Due to the low levels of enalapril in breast milk, the amount ingested by infants is minimal, and no adverse effects are expected on breastfed infants.
◉ Effects on breastfed infants
No adverse reactions were reported in 4 breastfed infants. Mothers took 5 to 10 mg of enalapril orally daily.
◉ Effects on lactation and breast milk
In 15 postmenopausal women with hypertension (no prior lactation status specified), serum prolactin levels were reduced by 22% after 15 days of once-daily administration of enalapril 20 mg compared to the placebo group. Prolactin levels in mothers who have established lactation may not affect their ability to breastfeed. A woman with preeclampsia was treated with 10 mg of enalapril daily at term. She began lactating on day 3 postpartum and breastfed without difficulty during a 5-week observation period. Protein Binding: Limited data from studies on the binding of enalapril in human plasma via balanced dialysis and…ultrafiltration have reported that enalapril binds to human plasma proteins at a rate of less than 50%. Interactions: The antihypertensive effect of enalapril is enhanced when used in combination with diuretics or other antihypertensive agents. This effect is often used for treatment, but dosage must be carefully adjusted when using these drugs concurrently. …Enalapril and diuretics appear to have an additive antihypertensive effect; however, severe hypotension and reversible renal insufficiency may occasionally occur, especially in patients with volume and/or sodium deficiency. Antihypertensive agents that induce renin release (such as diuretics) can enhance the antihypertensive effect of enalapril. Patients taking enalapril should use potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene), potassium supplements, or potassium-containing salt substitutes with caution, and serum potassium levels should be monitored frequently as hyperkalemia may occur. Because ACE inhibitors may promote the inhibition of kinin-mediated…prostaglandin synthesis and/or release, concomitant use of drugs that inhibit prostaglandin synthesis (e.g., aspirin, ibuprofen) may reduce the antihypertensive response of ACE inhibitors (including enalapril). Limited data suggest that concomitant use of ACE inhibitors with nonsteroidal anti-inflammatory drugs (NSAIDs) can sometimes lead to an acute decline in renal function; however, the possibility that such an effect may occur when one of these drugs is used alone cannot be ruled out. …Aspirin and other NSAIDs may also attenuate the hemodynamic effects of ACE inhibitors in patients with congestive heart failure. Because ACE inhibitors interact with and enhance the compensatory hemodynamic mechanisms of heart failure, and aspirin and other NSAIAs interact with these compensatory mechanisms rather than the ACE inhibitors themselves, these beneficial mechanisms are particularly vulnerable to this interaction, potentially leading to loss of clinical benefit. Therefore, the more severe the heart failure and the more pronounced the compensatory mechanisms, the more significant this effect. Interactions between nonsteroidal anti-inflammatory drugs (NSAIDs) and angiotensin-converting enzyme inhibitors (ACEIs). Even with optimal doses of ACEIs in the treatment of congestive heart failure, potential cardiovascular and survival benefits may not be observable if patients are concurrently taking NSAIAs. In multiple multicenter studies, concomitant administration of NSAIAs (e.g., a single dose of 350 mg aspirin) in patients with congestive heart failure has suppressed the beneficial hemodynamic effects associated with ACEIs, thereby diminishing the beneficial effects of these drugs on survival and cardiovascular disease incidence. /ACEI/
Lithium toxicity has been observed after concomitant administration of enalapril and lithium carbonate, which is reversible upon discontinuation of both drugs. In one patient, lithium poisoning was associated with elevated plasma lithium concentrations, manifesting as ataxia, dysarthria, tremor, confusion, and EEG changes, as well as bradycardia and T-wave depression. Elevated creatinine (2.2 mg/dL) or acute renal failure has also been observed in patients with moderate renal insufficiency (serum 100 mmol/L). The exact mechanism of this interaction remains to be determined, but studies suggest that enalapril may reduce renal clearance of lithium, possibly due to decreased aldosterone secretion leading to increased sodium excretion, or angiotensin-converting enzyme inhibition causing renal function changes.
Concomitant use of enalapril with certain vasodilators (e.g., nitrates) or anesthetics may lead to an excessive hypotensive response. Patients receiving enalapril concomitantly with nitrates or anesthetics that can cause hypotension should be closely monitored to prevent additive hypotensive effects. If hypotension during surgery or anesthesia is believed to be caused by enalapril's inhibition of angiotensin II production (secondary to compensatory renin release), hypotension can be corrected by volume expansion.

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Non-human toxicity values
Mouse LD50: Oral 2000-3500 mg/kg /enalapril maleate/
LD50: Male rats: Oral 2000-3500 mg/kg /enalapril maleate/
LD50: Female rats: Oral 2000-3000 mg/kg /enalapril maleate/
LD50: Male rats: Subcutaneous injection 1750 mg/kg /enalapril maleate/
For more complete non-human toxicity data for enalapril (out of 10), please visit the HSDB records page.

[1]. Comparison of captopril and enalapril to study the role of the sulfhydryl-group in improvement of endothelial dysfunction with ACE inhibitors in high dieted methionine mice. J Cardiovasc Pharmacol, 2006. 47(1): p. 82-8.

Therapeutic Uses
Angiotensin-converting enzyme inhibitors; antihypertensive drugs. ClinicalTrials.gov is a registry and results database that indexes human clinical studies funded by public and private institutions worldwide. The website is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each record on ClinicalTrials.gov includes a summary of the study protocol, including: the disease or condition; the intervention (e.g., the medical product, behavior, or procedure under investigation); the title, description, and design of the study; participation requirements (eligibility criteria); the location of the study; contact information for the study location; and links to relevant information from other health websites, such as the NLM's MedlinePlus (for patient health information) and PubMed (for citations and abstracts of academic articles in the medical field). Enalapril is indexed in the database. Enalapril maleate tablets are indicated for the treatment of hypertension. Enalapril maleate tablets can be used alone or in combination with other antihypertensive drugs, especially thiazide diuretics. The antihypertensive effects of enalapril maleate tablets and thiazide diuretics are roughly additive. /US product label contains/
Enalapril maleate tablets are indicated for the treatment of symptomatic congestive heart failure, usually used in combination with diuretics and digitalis. /US product label contains/
For more complete data on the therapeutic uses of enalapril (9 types), please visit the HSDB record page.

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Drug Warning
/Black Box Warning/ Enalapril maleate tablets should be discontinued as soon as pregnancy is discovered. Drugs that act directly on the renin-angiotensin system can cause injury or even death to the developing fetus.
The most common cardiovascular adverse reaction of enalapril or enalaprilat is hypotension (including orthostatic hypotension and other recurrent hypotension), which occurs in approximately 1-2% of hypertensive patients and 5-7% of heart failure patients after first use or during long-term treatment. Syncope occurs in approximately 0.5% and 2% of hypertensive or heart failure patients, respectively. Approximately 0.1% and 2% of patients with hypertension or heart failure receiving enalapril treatment require discontinuation due to hypotension or syncope. Use of drugs acting on the renin-angiotensin system in the second and third trimesters of pregnancy can reduce fetal kidney function, increasing fetal and neonatal morbidity and mortality. Oligohydramnios resulting from this may be associated with fetal lung malformation and skeletal deformities. Potential neonatal adverse reactions include craniosynostosis, anuria, hypotension, renal failure, and death. Enalapril maleate tablets should be discontinued as soon as pregnancy is confirmed. These adverse reactions are commonly associated with use of such drugs in the second and third trimesters. Most epidemiological studies investigating fetal malformations following early pregnancy use of antihypertensive drugs have not differentiated between drugs affecting the renin-angiotensin system and other antihypertensive drugs. Appropriate management of maternal hypertension during pregnancy is crucial for optimizing maternal and infant outcomes. Angioedema may occur, especially after the first dose of enalapril, and can be fatal if accompanied by laryngeal edema. If stridor or angioedema of the face, extremities, lips, tongue, or glottis occurs, enalapril should be discontinued, and the patient should be closely monitored until the swelling subsides. If the swelling is limited to the face and lips, it usually resolves spontaneously without treatment; however, antihistamines can relieve symptoms. Swelling of the tongue, glottis, or larynx may lead to airway obstruction, and appropriate treatment should be initiated immediately (e.g., administration of epinephrine, maintaining an airway patency). Patients should be informed that swelling of the face, eyes, lips, or tongue, or difficulty breathing, may be signs and symptoms of angioedema, and if any of these occur, enalapril should be discontinued immediately and a doctor notified. Patients with a history of angioedema unrelated to angiotensin-converting enzyme inhibitors may have an increased risk of developing angioedema while taking enalapril. Enalapril is contraindicated in patients with a history of angioedema associated with angiotensin-converting enzyme inhibitor treatment. Enalapril is contraindicated in patients with a known hypersensitivity to enalapril or any component of its formulations. For more complete data on enalapril warnings (28 in total), please visit the HSDB record page.

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Pharmacodynamics
Enalapril is an antihypertensive drug with natriuretic and uricosuric effects. Enalapril lowers blood pressure in patients with all levels of essential hypertension and renovascular hypertension, and reduces peripheral vascular resistance without increasing heart rate. It remains effective in patients with low-renin hypertension. Following the first oral single dose of enalapril, the blood pressure-lowering effect on systolic and diastolic blood pressure lasts for at least 24 hours. Repeated daily administration of enalapril can further lower blood pressure; achieving steady-state blood pressure control may take several weeks. In patients with severe congestive heart failure who do not respond well to conventional antihypertensive therapy, enalapril treatment can improve cardiac function, manifested as a reduction in both preload and afterload, and long-term improvement in clinical condition. In addition, enalapril can increase cardiac output and stroke volume in patients with congestive heart failure who are unresponsive to conventional digitalis and diuretic therapy, while reducing pulmonary capillary wedge pressure. Clinical studies have shown that enalapril can reduce left ventricular mass without affecting cardiac function or myocardial perfusion during exercise. Unlike most diuretics and beta-blockers, enalapril has a low risk of causing bradycardia and does not cause rebound hypertension after discontinuation. Enalapril has been reported not to cause hypokalemia, hyperglycemia, hyperuricemia, or hypercholesterolemia. Renally, enalapril increases renal blood flow and reduces renal vascular resistance. It also improves glomerular filtration rate in patients with a glomerular filtration rate below 80 mL/min. When used in combination with hydrochlorothiazide, enalapril can reduce drug-induced hypokalemia and enhance the antihypertensive effects of both drugs.

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Enalapril maleate (MK-421) is a prodrug of angiotensin-converting enzyme inhibitor (ACEI), which is metabolized in vivo to the active form enalaprilat, which exerts its pharmacological effects by inhibiting ACE.
- In a high-methionine-induced endothelial dysfunction model, enalapril maleate (MK-421) not only improved endothelial function by inhibiting ACE (reducing the synthesis of angiotensin II), but also by reducing oxidative stress (downregulating p47phox) and enhancing NO bioavailability (upregulating eNOS expression).
- Compared with captopril (another ACEI containing a thiol group), enalapril maleate (MK-421) (which does not contain a thiol group) still significantly improved endothelial dysfunction, indicating that a thiol group is not a necessary condition for ACE inhibitors to improve endothelial dysfunction [1]

C20H28N2O5.C4H4O4

492.52

492.21

76095-16-4

Enalapril-d5 maleate;349554-02-5;Enalapril;75847-73-3

5388962

White to off-white solid powder

0ºC

143-144.5ºC

0°C

1.645

2

6

10

27

519

3

CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N2CCC[C@H]2C(=O)O

OYFJQPXVCSSHAI-QFPUQLAESA-N

InChI=1S/C20H28N2O5.C4H4O4/c1-3-27-20(26)16(12-11-15-8-5-4-6-9-15)21-14(2)18(23)22-13-7-10-17(22)19(24)25;5-3(6)1-2-4(7)8/h4-6,8-9,14,16-17,21H,3,7,10-13H2,1-2H3,(H,24,25);1-2H,(H,5,6)(H,7,8)/b;2-1-/t14-,16-,17-;/m0./s1

(Z)-but-2-enedioic acid;(2S)-1-[(2S)-2-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]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

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)

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.)