| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 1g | |||
| Other Sizes |
| Targets |
Candoxatril is a neutral endopeptidase (NEP) inhibitor. [2]
|
|---|---|
| ln Vivo |
NEP inhibitors raise urinary cGMP levels and have an anti-inflammatory effect on hematopoiesis, but they have no discernible effect on body weight, food and water intake, mean blood pressure, or creatinine levels. Additionally, there was an inverse correlation between the deposition of a-SMA in the renal cortex and the rise of cGMP, indicating an antifibrotic action dependent on NEP. Each treatment group's high-quality mRNA profiles were produced using a minimum of 8 separate samples. Information supports the potential therapeutic use of this neutral endopeptidase inhibitor and corroborates the cGMP-dependent antifibrotic actions of Sol-1 [2].
In a mouse unilateral ureteral obstruction (UUO) model of kidney fibrosis, treatment with candoxatril for 1 week increased urinary cGMP levels and reduced collagen deposition (from 1.8% ± 1.4% to 0.8% ± 0.3%, P < 0.05) and α-SMA content (from 8.3% ± 3.8% to 4.9% ± 1.9%, P < 0.05) in the kidney cortex, indicating antifibrotic effects. [2] |
| Animal Protocol |
Mice were subjected to unilateral ureteral obstruction (UUO) and treated for 1 week with candoxatril (as a reference NEP inhibitor), compared to sham-operated animals and other treatment groups (solvent, SOL-1, losartan). [2]
|
| Toxicity/Toxicokinetics |
In the UUO mouse model, candoxatrozine had no significant effect on body weight, food and water intake, mean blood pressure, or creatinine levels. [2]
|
| References |
|
| Additional Infomation |
Candoxatril is the 2,3-dihydro-1H-inden-5-yl ester of the active enantiomer of Candoxatril. Candoxatril is the oral active prodrug of Candoxatril, a potent neutral endopeptidase (NEP, enkephalinase) inhibitor used to treat chronic heart failure. It is an EC 3.4.24 (metalloendopeptidase) inhibitor. It is a monocarboxylic acid, dicarboxylic acid monoester, and monocarboxylic acid amide. It is functionally related to indan-5-ol and Candoxatril. Candoxatril is the oral active prodrug of Candoxatril (UK-73967), a potent neutral endopeptidase (NEP) inhibitor. Mechanism of Action: Neutral endopeptidase inhibitors such as Candoxatril have a dual mechanism of action. They inhibit two metalloproteinases—neutral endopeptidase and angiotensin-converting enzyme (ACE)—thereby increasing the availability of natriuretic peptides, which have vasodilatory effects and may have tissue protective effects.
This study used candoxatro as a reference neutral endopeptidase inhibitor. Some studies have shown that NEP inhibitors may exert antifibrotic effects by increasing cGMP levels, possibly by preventing the degradation of endothelial-derived C-type natriuretic peptide (CNP), which has cGMP-dependent antifibrotic properties. [2] |
| Molecular Formula |
C29H41NO7
|
|---|---|
| Molecular Weight |
515.63834
|
| Exact Mass |
515.288
|
| CAS # |
123122-55-4
|
| PubChem CID |
5362417
|
| Appearance |
White to off-white solid powder
|
| Density |
1.21g/cm3
|
| Boiling Point |
718.4ºC at 760mmHg
|
| Flash Point |
388.3ºC
|
| LogP |
4.91
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
13
|
| Heavy Atom Count |
37
|
| Complexity |
772
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
COCCOC[C@H](CC1(CCCC1)C(=O)NC2CCC(CC2)C(=O)O)C(=O)OC3=CC4=C(CCC4)C=C3
|
| InChi Key |
ZTWZVMIYIIVABD-RZMWZJFBSA-N
|
| InChi Code |
InChI=1S/C29H41NO7/c1-35-15-16-36-19-23(27(33)37-25-12-9-20-5-4-6-22(20)17-25)18-29(13-2-3-14-29)28(34)30-24-10-7-21(8-11-24)26(31)32/h9,12,17,21,23-24H,2-8,10-11,13-16,18-19H2,1H3,(H,30,34)(H,31,32)/t21?,23-,24?/m0/s1
|
| Chemical Name |
4-[[1-[(2S)-3-(2,3-dihydro-1H-inden-5-yloxy)-2-(2-methoxyethoxymethyl)-3-oxopropyl]cyclopentanecarbonyl]amino]cyclohexane-1-carboxylic acid
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9393 mL | 9.6967 mL | 19.3934 mL | |
| 5 mM | 0.3879 mL | 1.9393 mL | 3.8787 mL | |
| 10 mM | 0.1939 mL | 0.9697 mL | 1.9393 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
