| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Integrin alpha4beta1 (VLA-4; CD49d/CD29) and alpha4beta7 (LPAM-1).
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|---|---|
| ln Vitro |
The ubiquitous L-phenylalanine-N-aroyl motif found in valategrast is where the carboxylic acid binds to metal ions in metal ion-dependent adhesion sites (MIDAS) [2].
In cell-free SPR binding assay, valategrast binds to human alpha4beta1 with Kd ~3 nM and to alpha4beta7 with Kd ~9 nM. Inhibits VCAM-1 binding to alpha4beta1 with IC50 of 2.7 nM (ELISA). Also blocks MAdCAM-1 binding to alpha4beta7 with IC50 12 nM. |
| ln Vivo |
In ovalbumin-sensitized mouse asthma model, oral valategrast (10 mg/kg b.i.d.) reduces bronchoalveolar lavage eosinophils by 85% and airway hyperresponsiveness by 60%. In IL-10 knockout mouse colitis model, 30 mg/kg/day p.o. reduces colon inflammation score from 3.5 to 1.2.
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| Enzyme Assay |
Solid-phase binding assay: 96-well plate coated with recombinant VCAM-1 (5 ug/mL); blocked with BSA; purified human alpha4beta1 (0.5 nM) plus 0-100 nM valategrast incubated 2 h at RT; bound integrin detected by anti-alpha4 mAb and HRP-conjugated secondary; IC50 calculated using 4-parameter fit.
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| Cell Assay |
Jurkat T cell adhesion assay: cells pre-incubated with valategrast (0.1-100 nM) for 30 min, then plated on VCAM-1-coated wells; unbound cells washed with PBS; adherent cells quantified by crystal violet staining (OD595) or calcein-AM fluorescence; IC50 for adhesion inhibition ≈ 5 nM.
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| Animal Protocol |
Mouse airway inflammation model: BALB/c mice sensitized with OVA/alum on days 0 and 14; challenged with OVA aerosol on days 21-23; valategrast (1, 3, 10 mg/kg p.o.) given 1 h before each challenge; 24 h after final challenge, BALF collected for eosinophil count (Wright-Giemsa stain) and IL-5/IL-13 ELISA.
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| ADME/Pharmacokinetics |
Rat p.o. 10 mg/kg: Cmax ~2.1 uM at 2 h; bioavailability ~45%; t1/2 ~3.4 h; plasma protein binding ~98%; minimal brain penetration; metabolized by CYP3A4 to inactive products; excreted mainly in feces.
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| Toxicity/Toxicokinetics |
Well tolerated in animal studies up to 200 mg/kg/day. No significant hematologic or hepatic toxicity. Human trials: mild headaches and gastrointestinal upset (5-10%). No immunosuppression-related infections reported at therapeutic doses.
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| References | |
| Additional Infomation |
Discontinued after Phase II trials for asthma and ulcerative colitis due to insufficient efficacy over placebo. Later investigated for dry eye disease (topical formulation). Not FDA-approved. Provided a valuable scaffold for alpha4 integrin antagonist development (e.g., natalizumab successor small molecules).
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| Molecular Formula |
C30H32CL3N3O4
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|---|---|
| Molecular Weight |
604.9518
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| Exact Mass |
603.146
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| CAS # |
220847-86-9
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| Related CAS # |
Valategrast hydrochloride;828271-96-1
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| PubChem CID |
11563636
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
7.081
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
40
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| Complexity |
812
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCN(CC)CCOC(=O)[C@H](CC1=CC=C(C=C1)NC(=O)C2=C(C=CC=C2Cl)Cl)NC(=O)C3=C(C=CC=C3Cl)C
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| InChi Key |
VZVNFRFMDNFPOM-VWLOTQADSA-N
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| InChi Code |
InChI=1S/C30H32Cl3N3O4/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)/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
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
DMSO : ~170 mg/mL (~281.01 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.25 mg/mL (7.03 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 42.5 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. Solubility in Formulation 2: ≥ 4.25 mg/mL (7.03 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 42.5 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. View More
Solubility in Formulation 3: ≥ 4.25 mg/mL (7.03 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6530 mL | 8.2651 mL | 16.5303 mL | |
| 5 mM | 0.3306 mL | 1.6530 mL | 3.3061 mL | |
| 10 mM | 0.1653 mL | 0.8265 mL | 1.6530 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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