Angiotensin-converting enzyme (ACE). No IC50, Ki, EC50, or DC50 values are provided in this study. [1]

Cilazapril is one of the angiotensin-converting enzyme inhibitors (ACE inhibitors) used for hypertension.

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Cilazapril (1 mg/kg, daily) tends to decrease and the higher dose (10 mg/kg, daily) significantly decreases systolic blood pressure (SBP) in subtotal nephrectomized rats. Cilazapril attenuates the further development of protein uria in a dose-dependent manner in subtotal nephrectomized rats. Cilazapril attenuates the increase in plasma fibrinogen concentration and serum albumin concentration in a dose-dependent manner. Cilazapril reduces serum MCP-1 concentration in the nephrectomized rats. Cilazapril decreases hepatic fibrinogen synthesis through the alleviation of the local inflammatory process and the improvement of hypoalbuminemia. Cilazapril normalizes systolic arterial pressure to 121 mm Hg (SD) in the treated SHR-SP rats. Cilazapril decreases systolic arterial pressure to a nearly normal level and prevents hypertensive retinal vascular changes, probably by improving endothelial function. Cilazapril results in a marked decrease in the Kd of the renal arginine vasopressin (AVP) receptor and an increase in the plasma AVP level in the spontaneously hypertensive rat. Cilazapril exerts a rapid, complete, and persistent antihypertensive effect in the spontaneously hypertensive rats (SHR) in vivo but has no effect on SAP in the normotensive Sprague-Dawley rat. Cilazapril treatment depresses heart performance (28-35%) in SHR but has no effect in the Sprague-Dawley rats. Cilazapril decreases blood pressure to control values and reduces HW:BW in hyperthyroid rats.
In 5/6 nephrectomized rats, Cilazapril Monohydrate (Ro 31-2848) attenuated the increase in plasma fibrinogen concentration in a dose-dependent manner. At 1 mg/kg per day, the increase was not significantly different from vehicle (P>0.1), while at 10 mg/kg per day, the increase was significantly attenuated (P<0.01). Over 12 weeks, plasma fibrinogen increased by 48.5 mg/dL in the low-dose group and 37.2 mg/dL in the high-dose group, compared to 55.0 mg/dL in vehicle-treated nephrectomized rats. [1]
Cilazapril Monohydrate (Ro 31-2848) reduced serum MCP-1 concentration in nephrectomized rats significantly (P<0.05 for low dose, P<0.01 for high dose vs. vehicle). Serum TGF-β1 was also reduced but not significantly. [1]
Cilazapril Monohydrate (Ro 31-2848) attenuated the further development of proteinuria in a dose-dependent manner. The higher dose (10 mg/kg per day) markedly reduced proteinuria to levels not significantly different from control rats. [1]
Cilazapril Monohydrate (Ro 31-2848) significantly increased serum albumin concentration in a dose-dependent manner (P<0.05 for low dose, P<0.01 for high dose vs. vehicle). [1]
Cilazapril Monohydrate (Ro 31-2848) lowered systolic blood pressure: 139±3 mmHg (low dose) and 127±4 mmHg (high dose) at end of treatment, with high dose significantly decreasing SBP (P<0.01 vs. vehicle, 146±4 mmHg). [1]

1 mg/kg Rats

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Male 6-week-old Wistar rats underwent 5/6 nephrectomy (ligation of renal artery branches supplying two-thirds of left kidney followed by right unilateral nephrectomy 7 days later). Eight weeks after operation, nephrectomized rats were divided into groups: vehicle (0.5% methyl cellulose solution), low-dose Cilazapril Monohydrate (Ro 31-2848) (1 mg/kg per day), and high-dose Cilazapril Monohydrate (Ro 31-2848) (10 mg/kg per day). Sham-operated controls received vehicle. Compounds dissolved in 0.5% methyl cellulose were given by gastric gavage once daily for 12 weeks. Blood pressure was measured by tail-cuff method in awake rats every 4 weeks. Urine protein excretion was determined biweekly from 4-h urine samples collected in metabolic cages following water loading (3% of body weight) by gastric gavage, normalized to urine creatinine concentration. At the end of treatment, blood was collected from abdominal aorta under pentobarbital anesthesia (50 mg/kg i.p.) for serum chemistries and MCP-1/TGF-β1 measurements. [1]

J Pharmacol Sci.2004 Jan;94(1):67-72;Life Sci.1999;64(3):PL27-39.

Cilazapril monohydrate is the monohydrate of cilazapril. It is used to treat hypertension and heart failure. It is an antihypertensive drug and also an EC 3.4.15.1 (peptidyl dipeptidase A) inhibitor and prodrug. It contains the cilazapril molecule. It is one of the angiotensin-converting enzyme inhibitors (ACE inhibitors) used to treat hypertension. It is a prodrug that is hydrolyzed after absorption to its main metabolite, cilazapril. See also: Cilapril (note moved to).

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Cilazapril Monohydrate (Ro 31-2848) is an angiotensin-converting enzyme (ACE) inhibitor. Its renoprotective effects in the remnant kidney model are thought to be mediated primarily through reduction of glomerular hypertension and hyperfiltration, as well as decreasing proteinuria, which in turn improves tubulointerstitial remodeling and alleviates local inflammation. The agent reduced serum MCP-1, suggesting inhibition of macrophage recruitment. Although ACE inhibitors can increase bradykinin, previous studies in renal ablation models indicate that bradykinin plays a minor role in the renoprotective effect. The study also notes that ACE inhibitors (including lisinopril, perindopril, and cilazapril) have been shown to reduce plasma fibrinogen in hypertensive patients and chronic heart failure, possibly through improvement of insulin sensitivity or anti-inflammatory actions. [1]

C22H31N3O5.H2O

435.51

435.237

92077-78-6

Cilazapril;88768-40-5

56329

White to off-white solid powder

598.1ºC at 760mmHg

98° (dec)

315.5ºC

1.797

3

8

9

31

608

3

CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]2CCCN3CCC[C@H](N3C2=O)C(=O)O.O

JQRZBPFGBRIWSN-YOTVLOEGSA-N

InChI=1S/C22H31N3O5.H2O/c1-2-30-22(29)18(13-12-16-8-4-3-5-9-16)23-17-10-6-14-24-15-7-11-19(21(27)28)25(24)20(17)26;/h3-5,8-9,17-19,23H,2,6-7,10-15H2,1H3,(H,27,28);1H2/t17-,18-,19-;/m0./s1

(4S,7S)-7-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]-6-oxo-1,2,3,4,7,8,9,10-octahydropyridazino[1,2-a]diazepine-4-carboxylic acid;hydrate

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)

Solubility in Formulation 1: ≥ 3 mg/mL (6.89 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 30.0 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: ≥ 3 mg/mL (6.89 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 30.0 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: ≥ 3 mg/mL (6.89 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 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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