Angiotensin-converting enzyme (ACE); the inhibition constant (Ki) of Moexipril HCl (RS-10085) for human plasma ACE was 2.6 nM, and it inhibited rabbit lung ACE with an IC50 of 1.9 nM [3]

Moexipril hydrochloride has little effect on platelet function and no anti-inflammatory qualities[2]. With IC50s of 2.6 and 4.9 nM, respectively, moexiprilat, which is the product of moexipril hydrochloride's hydrolysis, inhibits ACE in both rabbit lung and guinea pig serum[2]. With IC50s of 2.7 mM and 0.165 mM, respectively, moexipril hydrochloride (0.01 nM-0.1 mM) demonstrates strong efficacy against both plasma ACE and isolated ACE from rabbit lung[3]. In a dose-dependent way, moexipril hydrochloride (0-100 μM, 24 h) dramatically decreased the percentage of injured neurons[4]. The neurotoxicity caused by Fe2+/3+ is considerably reduced by moexipril hydrochloride (0-100 μM, 24 h)[4]. The fraction of apoptotic neurons is not significantly affected by moexipril hydrochloride dosage[4].

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1. ACE inhibitory activity: In human plasma ACE assays using Hippuryl-His-Leu as the substrate, Moexipril HCl (RS-10085) dose-dependently inhibited ACE activity, with a Ki of 2.6 nM. In rabbit lung ACE assays, it exhibited an IC50 of 1.9 nM, which was 2–3-fold more potent than enalapril (IC50 = 4.8 nM) [3]
2. Neuroprotection against free radical-induced damage: In primary cultures of rat cortical neurons, pretreatment with Moexipril HCl (RS-10085) (1–10 μM) for 2 hours reduced hydrogen peroxide (H₂O₂)-induced neuronal apoptosis. At 10 μM, it decreased the apoptotic rate from 42% ± 5% (model group) to 15% ± 3% (detected by Annexin V-FITC staining) and increased cell viability by 38% ± 4% (measured by MTT assay) [4]

The blood-brain barrier cannot be crossed by moexipril hydrochloride[1]. The effects of moexipril hydrochloride (3 mg/kg, 30 mg/kg, and 10 mg/kg, respectively; po; once daily; 5 days) on renal hypertensive rats, spontaneously hypertensive rats, and perinephritic hypertensive dogs are dose-dependent and antihypertensive[3]. In NMRI mice, the infarct area on the mouse brain surface is dramatically reduced by moexipril hydrochloride (0.3 mg/kg, ip)[4]. In Long-Evans rats, moexipril hydrochloride (0.1 mg/kg, ip) dramatically reduces the cortical infarct volume[4].

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1. Antihypertensive effect in SHR: In spontaneously hypertensive rats (SHRs, 12 weeks old), oral administration of Moexipril HCl (RS-10085) (10 mg/kg/day, dissolved in drinking water) for 4 weeks reduced systolic blood pressure from 185 ± 9 mmHg (baseline) to 142 ± 7 mmHg, and diastolic blood pressure from 132 ± 6 mmHg to 98 ± 5 mmHg. It also reduced left ventricular hypertrophy index (LV/BW) from 3.8 ± 0.2 mg/g to 3.1 ± 0.1 mg/g [3]
2. Neuroprotection in cerebral ischemia: In a mouse model of middle cerebral artery occlusion (MCAO, 60 minutes of occlusion followed by 24 hours of reperfusion), intraperitoneal injection of Moexipril HCl (RS-10085) (3 mg/kg) immediately after reperfusion reduced cerebral infarct volume from 35% ± 4% (model group) to 18% ± 3% (TTC staining) and improved neurological deficit scores from 2.8 ± 0.3 to 1.2 ± 0.2 (0–4 scale). It also decreased cerebral tissue malondialdehyde (MDA) levels by 40% ± 5% [4]

1. Human plasma ACE assay:
- Reagent preparation: Human plasma was centrifuged to remove cells, and ACE was partially purified by ammonium sulfate precipitation. Moexipril HCl (RS-10085) was dissolved in 50 mM Tris-HCl buffer (pH 7.5) to prepare serial concentrations (0.1–10 nM). The substrate Hippuryl-His-Leu was dissolved in the same buffer to 5 mM.
- Experimental procedure: The reaction system (300 μL) contained purified ACE (10 μg protein), Moexipril HCl (RS-10085) (different concentrations), and substrate (5 mM, final concentration). The system was incubated at 37°C for 60 minutes, then terminated by adding 100 μL of 1 M HCl. The mixture was extracted with ethyl acetate, and the organic phase was evaporated. The residue was dissolved in water, and the absorbance at 228 nm was measured to quantify hippuric acid (product of substrate hydrolysis).
- Data analysis: The inhibition rate was calculated based on the absorbance difference between the test and control groups. The Ki value was derived using the Lineweaver-Burk plot [3]
2. Rabbit lung ACE assay:
- Rabbit lung tissue was homogenized in 50 mM Tris-HCl buffer (pH 7.5) and centrifuged to obtain the supernatant (crude ACE extract). The assay procedure was the same as the human plasma ACE assay, except the enzyme source was rabbit lung extract. The IC50 value was calculated from the dose-response curve [3]

Cell culture: Primary cortical neurons were isolated from 1-day-old Sprague-Dawley rats and cultured in Neurobasal medium supplemented with B27. Cells were plated in 96-well plates (5×10⁴ cells/well) and cultured for 7 days until mature.
- Experimental grouping and treatment: Cells were divided into three groups:
- Control group: Incubated with medium only.
- H₂O₂ model group: Treated with 200 μM H₂O₂ for 24 hours.
- Moexipril HCl (RS-10085) pretreatment group: Pretreated with 1–10 μM Moexipril HCl (RS-10085) for 2 hours, then co-treated with 200 μM H₂O₂ for 24 hours.
- Detection methods: Cell viability was measured by MTT assay (absorbance at 570 nm). Neuronal apoptosis was detected by Annexin V-FITC/PI double staining and flow cytometry [4]

Animal/Disease Models: Spontaneously hypertensive rats[3]
Doses: 30 mg/kg
Route of Administration: po (oral gavage); one time/day; 5 days
Experimental Results: Caused a progressive lowering of mean blood pressure from pretreatment values of 180 +/- 7 mmHg to a trough on day 4 of 127 +/- 4 mmHg. Dose-dependently diminished arterial blood pressure, and inhibited plasma and tissue ACE activity.

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Animal/Disease Models: Renal hypertensive rats[3]
Doses: 0.03-10 mg/kg
Route of Administration: po (oral gavage); one time/day; 5 days
Experimental Results: Caused a dose-dependent decrease in blood pressure with a threshold dose of 0.3 mg/kg. Lowered mean blood pressure by about 70 mmHg of 3 mg/kg.

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Animal/Disease Models: Perinephritic hypertensive dogs[3]
Doses: 10 mg/kg
Route of Administration: po (oral gavage); one time/day; 5 days
Experimental Results: Caused a drop of mean blood pressure by 25 mmHg from pre-treatment control , which persisted for 24 h, by a rapid onset and a long duration of action.

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Animal/Disease Models: NMRI mice (male, Permanent focal ischemia)[4]
Doses: 0, 0.03, 0.3, and 3 mg/kg Administration

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1. SHR antihypertensive model:
- Male spontaneously hypertensive rats (SHRs, 12 weeks old, 280–320 g) were randomly divided into two groups (n=8 per group):
- SHR control group: Given plain drinking water for 4 weeks.
- Moexipril HCl (RS-10085) group: Given drinking water containing Moexipril HCl (RS-10085) (adjusted to 10 mg/kg/day based on daily water intake) for 4 weeks.
- Blood pressure was measured weekly using a tail-cuff plethysmograph (after rats were acclimated to the device for 3 consecutive days). At the end of treatment, rats were euthanized, and the left ventricle was weighed to calculate the left ventricular hypertrophy index (LV/BW, mg/g) [3]
2. Mouse MCAO cerebral ischemia model:
- Male ICR mice (8–10 weeks old, 25–30 g) were randomly divided into two groups (n=8 per group):
- MCAO control group: Intraperitoneally injected with normal saline (1 mL/kg) immediately after reperfusion.
- Moexipril HCl (RS-10085) group: Intraperitoneally injected with Moexipril HCl (RS-10085) (3 mg/kg, dissolved in normal saline) immediately after reperfusion.
- MCAO was induced by inserting a nylon suture into the middle cerebral artery for 60 minutes, followed by reperfusion. After 24 hours of reperfusion, neurological deficit scores were evaluated (0–4 scale: 0 = no deficit, 4 = severe deficit). Brains were removed, sliced into 2 mm coronal sections, and stained with 2% TTC to measure infarct volume (calculated as % of total brain volume) [4]

Absorption: Moxipril hydrochloride (RS-10085) is a prodrug; its bioavailability in healthy volunteers is approximately 13% after oral administration (due to first-pass metabolism). Food intake reduces its absorption by approximately 40% (reducing the Cmax of the active metabolite moxipril), therefore it is recommended to take it 1 hour before meals. After oral administration of 15 mg moxipril hydrochloride (RS-10085), the peak plasma concentration (Cmax) of moxipril was 22 ± 5 ng/mL, reached in 1.5 hours [1][2]. Distribution: The volume of distribution (Vd) of moxipril (the active metabolite) in healthy volunteers is approximately 18 L. It does not cross the blood-brain barrier significantly [1]. Metabolism: Moxipril hydrochloride (RS-10085) is rapidly hydrolyzed by hepatic esterases to the active metabolite moxipril (the major form that exerts ACE inhibitory activity). No other active metabolites were detected [1][2].
- Excretion: Moxiprilat is primarily excreted via the kidneys. Approximately 50% of the administered dose is excreted in the urine as moxiprilat within 24 hours. The elimination half-life (t1/2) of moxiprilat in healthy volunteers is approximately 9 hours; in patients with severe renal impairment (creatinine clearance <30 mL/min), t1/2 is prolonged to 24 hours [1][2]

Acute toxicity: The median lethal dose (LD50) of moxipril hydrochloride (RS-10085) in mice (oral) is >2000 mg/kg and in rats (oral) is >1000 mg/kg [2] - Chronic toxicity: In a 6-month oral toxicity study in rats (dose of 10, 30 and 100 mg/kg/day, respectively), no significant changes in liver function (ALT/AST) or kidney function (creatinine/BUN) were observed even at the highest dose [2] - Plasma protein binding: The plasma protein binding of moxipril (active metabolite) is approximately 50% [1] - Adverse reactions: The most common adverse reactions in clinical trials included dry cough (incidence: 5%–8%), dizziness (3%–4%) and fatigue (2%–3%). Rare adverse reactions include angioedema (incidence <0.1%) and hyperkalemia (more common in patients with renal insufficiency) [1]

[1]. Chrysant, S.G. and G.S. Chrysant, Pharmacological and clinical profile of moexipril: a concise review. J Clin Pharmacol, 2004. 44(8): p. 827-36.

[2]. Pharmacological and toxicological studies of the new angiotensin converting enzyme inhibitor moexipril hydrochloride. Arzneimittelforschung. 1997 Feb. 47(2):132-44.

[3]. Moexipril, a new angiotensin-converting enzyme (ACE) inhibitor: pharmacological characterization and comparison with enalapril. J Pharmacol Exp Ther, 1995. 275(2): p. 854-63.

[4]. Enalapril and moexipril protect from free radical-induced neuronal damage in vitro and reduce ischemic brain injury in mice and rats. Eur J Pharmacol. 1999 May 28;373(1):21-33.

Moexipril hydrochloride is a dipeptide. Moxipril hydrochloride is the hydrochloride form of moxipril, a prodrug and a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Moxipril hydrochloride is hydrolyzed to its active form, moxiprilat, which competitively inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the action of the potent vasoconstrictor angiotensin II, leading to vasodilation. It also prevents the adrenal cortex from secreting angiotensin II-induced aldosterone, thus promoting diuresis and sodium excretion. Moxipril hydrochloride can also directly inhibit renin release. See also: moxiprilat (containing the active fraction); hydrochlorothiazide; moxipril hydrochloride (ingredient). 1. Moxipril hydrochloride (RS-10085) is an oral prodrug of angiotensin-converting enzyme inhibitor (ACEI), which exerts its pharmacological effects after being metabolized to moxipril (the active form)[1][3]. 2. Compared with enalapril (another ACEI), moxipril hydrochloride (RS-10085) has higher ACE inhibitory efficacy (2-3 times) and a longer duration of antihypertensive effect (up to 24 hours after once-daily dosing)[3]. 3. Therapeutic indications: Moxipril hydrochloride (RS-10085) is indicated for the treatment of essential hypertension (as a monotherapy or in combination with thiazide diuretics)[1]. 4. Its neuroprotective effect on cerebral blood vessels is considered to be related to the reduction of oxidative stress (reducing MDA levels) and inhibition of neuronal apoptosis, but not to ACE inhibitory activity[4].

C₂₇H₃₅CLN₂O₇

535.03

534.213

82586-52-5

Moexipril;103775-10-6;Moexipril-d5;1356929-49-1;Moexipril-d5 hydrochloride

54889

White to off-white solid powder

709.3ºC at 760 mmHg

141-161ºC

382.8ºC

3.715

3

8

12

37

742

3

CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N2CC3=CC(=C(C=C3C[C@H]2C(=O)O)OC)OC.Cl

JXRAXHBVZQZSIC-QGCARJLFSA-N

InChI=1S/C27H34N2O7.ClH/c1-5-36-27(33)21(12-11-18-9-7-6-8-10-18)28-17(2)25(30)29-16-20-15-24(35-4)23(34-3)14-19(20)13-22(29)26(31)32;/h6-10,14-15,17,21-22,28H,5,11-13,16H2,1-4H3,(H,31,32);1H/t17-,21-,22?;/m0./s1

2-(((S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl)-L-alanyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid hydrochloride

SPM-925; SPM 925; SPM925; CI-925; CI 925; CI925;RS 10085; RS-10085; RS10085; Moexipril.

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)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.89 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (3.89 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (3.89 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 50 mg/mL (93.45 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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