| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
| 500mg | |||
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| Other Sizes |
| Targets |
Valategrast targets integrin α4β1 (VLA-4, very late antigen-4) and integrin α4β7. These integrins are cell adhesion molecules that mediate the adhesion of leukocytes to vascular endothelium and their subsequent migration into tissues. α4β1 is involved in the recruitment of lymphocytes, monocytes, and eosinophils to sites of inflammation, while α4β7 is primarily involved in gut homing of lymphocytes. By antagonizing both integrins, Valategrast inhibits leukocyte adhesion, rolling, and transmigration across the endothelium. This dual antagonism provides a comprehensive approach to inhibiting leukocyte trafficking in inflammatory diseases such as asthma and COPD.
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| ln Vitro |
The common L-phenylalanine-N-aroyl motif seen in valategrast (hydrochloride) is where the carboxylic acid binds to metal ions in metal ion-dependent adhesion sites (MIDAS) [2].
In vitro, Valategrast is a potent dual antagonist of integrin α4β1 and α4β7. The compound inhibits leukocyte adhesion to VCAM-1 (vascular cell adhesion molecule-1) and MAdCAM-1 (mucosal addressin cell adhesion molecule-1), the respective ligands for α4β1 and α4β7. Its potency and selectivity have been characterized in cell adhesion assays using integrin-expressing cells. The compound's mechanism of action involves binding to the metal ion-dependent adhesion site (MIDAS) of the integrin. |
| ln Vivo |
In vivo, Valategrast has been studied for the potential treatment of asthma and COPD. By blocking integrin-mediated leukocyte trafficking, the compound reduces airway inflammation and hyperresponsiveness. Clinical trials have been conducted to evaluate its safety and efficacy in patients with asthma and COPD.
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| Enzyme Assay |
In vitro enzyme/receptor binding (non-cell) assays for Valategrast involve measuring its binding affinity to integrin α4β1 and α4β7. ELISA-based binding assays using purified integrin proteins and their ligands (VCAM-1, MAdCAM-1) are performed with varying concentrations of Valategrast. Binding affinity (IC50) is determined from competition curves.
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| Cell Assay |
In vitro cell-based experiments for Valategrast are conducted using leukocyte cell lines that express integrin α4β1 and α4β7. Adhesion assays are performed where cells are allowed to adhere to VCAM-1 or MAdCAM-1-coated surfaces in the presence of varying concentrations of Valategrast. The compound's ability to inhibit adhesion is quantified. Cell migration assays using transwell chambers are also performed.
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| Animal Protocol |
In vivo animal experiments for Valategrast are performed in animal models of asthma and COPD. Valategrast is administered orally or intravenously, and airway inflammation, hyperresponsiveness, and leukocyte infiltration are assessed. Clinical trials in humans have also been conducted.
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| ADME/Pharmacokinetics |
Valategrast hydrochloride is a small molecule (MW 641.41, formula C30H33Cl4N3O4) with suitable physicochemical properties for oral administration. Detailed pharmacokinetic parameters, including bioavailability, half-life, and clearance, are available from clinical studies.
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| Toxicity/Toxicokinetics |
Preclinical and clinical toxicology studies have been conducted to evaluate the safety profile of Valategrast. The compound is generally well-tolerated at therapeutic doses. Clinical trials have evaluated the safety and efficacy of Valategrast in patients with asthma and COPD. The safety profile supports its continued development for inflammatory diseases.
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| References | |
| Additional Infomation |
See also: Valategrast (comment moved to).
Valategrast hydrochloride is also known as R411 and Ro 27-2441. It is a dual antagonist of integrin α4β1 (VLA-4) and α4β7 that has been studied for the potential treatment of asthma and COPD. Its dual antagonism provides a comprehensive approach to inhibiting leukocyte trafficking in inflammatory diseases. The compound is not approved for clinical use. |
| Molecular Formula |
C30H33CL4N3O4
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|---|---|
| Molecular Weight |
641.412724256516
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| Exact Mass |
639.123
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| CAS # |
828271-96-1
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| Related CAS # |
Valategrast;220847-86-9
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| PubChem CID |
11563635
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
7.883
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
41
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| Complexity |
812
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCN(CCOC([C@@H](NC(C1=C(C=CC=C1Cl)C)=O)CC2=CC=C(NC(C3=C(Cl)C=CC=C3Cl)=O)C=C2)=O)CC.Cl
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| InChi Key |
CNNHYZRRGXZIIA-UQIIZPHYSA-N
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| InChi Code |
InChI=1S/C30H32Cl3N3O4.ClH/c1-4-36(5-2)16-17-40-30(39)25(35-28(37)26-19(3)8-6-9-22(26)31)18-20-12-14-21(15-13-20)34-29(38)27-23(32)10-7-11-24(27)33;/h6-15,25H,4-5,16-18H2,1-3H3,(H,34,38)(H,35,37);1H/t25-;/m0./s1
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| Chemical Name |
2-(diethylamino)ethyl (2S)-2-[(2-chloro-6-methylbenzoyl)amino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoate;hydrochloride
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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
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| 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 | 1.5591 mL | 7.7953 mL | 15.5907 mL | |
| 5 mM | 0.3118 mL | 1.5591 mL | 3.1181 mL | |
| 10 mM | 0.1559 mL | 0.7795 mL | 1.5591 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.
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