| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
α4β1 α4β7
RO0270608 targets α4β1 (VLA-4) and α4β7 integrins, which are cell surface receptors involved in leukocyte adhesion and migration. These integrins mediate the adhesion of leukocytes to vascular endothelial cells via binding to VCAM-1 and MAdCAM-1, respectively. By antagonizing these integrins, RO0270608 inhibits the recruitment of inflammatory cells to sites of inflammation, thereby reducing tissue damage and inflammatory responses. |
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| ln Vitro |
At 33 nM, RO0270608 inhibits cell adhesion mediated by α4/β7. In an experiment for human T-cell VCAM/anti CD3 costimulation, RO0270608 significantly inhibits T-cell proliferation (IC50=30 nM)[2].
In vitro, RO0270608 inhibits α4/β7-mediated cell adhesion with an IC50 of 33 nM. In a human T-cell VCAM/anti-CD3 costimulation assay, RO0270608 causes a pronounced inhibition of T-cell proliferation with an IC50 of 30 nM. These data demonstrate potent inhibition of integrin-mediated cellular functions by the compound. |
| ln Vivo |
RO0270608 eliminates allergen-induced inflammatory cell accumulation in a mouse OVA-model of airway inflammation[2].
In vivo, RO0270608 eliminates allergen-induced inflammatory cell accumulation in a mouse OVA-model of airway inflammation. This demonstrates its anti-inflammatory activity in a relevant disease model. As the active metabolite of R411, which is orally active, RO0270608 is responsible for the in vivo pharmacological effects of the prodrug. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for RO0270608 involve measuring its ability to inhibit integrin-mediated cell adhesion. In a typical assay, cells expressing α4β1 or α4β7 integrins are allowed to adhere to immobilized VCAM-1 or MAdCAM-1 in the presence of increasing concentrations of RO0270608. The half-maximal inhibitory concentration (IC50) is determined by quantifying the percentage of adherent cells. In T-cell proliferation assays, human T cells are stimulated with anti-CD3 and VCAM-1, and proliferation is measured by [³H]-thymidine incorporation or CFSE dilution.
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| Cell Assay |
Cell-based assays for RO0270608 include adhesion assays and T-cell proliferation assays. In adhesion assays, cells expressing α4 integrins are incubated with the compound and then allowed to adhere to immobilized VCAM-1 or MAdCAM-1. In T-cell proliferation assays, human T cells are stimulated with anti-CD3 and VCAM-1 in the presence of RO0270608, and proliferation is measured. These assays quantify the compound's ability to inhibit integrin-mediated cellular functions.
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| Animal Protocol |
In vivo animal studies for RO0270608 are conducted in mouse models of allergic airway inflammation. In the OVA (ovalbumin)-induced airway inflammation model, mice are sensitized and challenged with OVA, and RO0270608 is administered to assess its ability to reduce inflammatory cell accumulation in the airways. Other models may include experimental autoimmune encephalomyelitis (EAE) or inflammatory bowel disease models where α4 integrins play a pathogenic role.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of RO0270608 are derived from studies of its prodrug R411. As the active metabolite, RO0270608 is responsible for the pharmacological activity following oral administration of R411. The compound has a molecular weight of 505.78 g/mol, a molecular formula of C24H19Cl3N2O4, and a logP of 6.097. It is soluble in DMSO (12.5 mg/mL). For storage, the powder can be kept at -20°C for 3 years or at 4°C for 2 years.
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| Toxicity/Toxicokinetics |
Toxicological data for RO0270608 are limited. As an integrin antagonist, it may have potential effects on immune function due to the role of α4 integrins in leukocyte trafficking. However, specific toxicology studies are not publicly available. For research use only, not for therapeutic or human use. The compound is intended for research purposes only.
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| References |
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| Additional Infomation |
RO0270608 (CAS# 220846-33-3) is the bioactive metabolite of R411 and is a dual α4β1/α4β7 integrin antagonist with anti-inflammatory activity. It inhibits α4/β7-mediated cell adhesion with an IC50 of 33 nM and inhibits T-cell proliferation with an IC50 of 30 nM. In vivo, it eliminates allergen-induced inflammatory cell accumulation in a mouse OVA-model of airway inflammation. The compound has a molecular weight of 505.78 g/mol and a molecular formula of C24H19Cl3N2O4. It is used in research on allergic inflammatory responses.
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| Molecular Formula |
C24H19CL3N2O4
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|---|---|
| Molecular Weight |
505.78
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| Exact Mass |
504.041
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| CAS # |
220846-33-3
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| PubChem CID |
16727128
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
6.097
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
691
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C(C(=CC=C1)Cl)C(=O)N[C@@H](CC2=CC=C(C=C2)NC(=O)C3=C(C=CC=C3Cl)Cl)C(=O)O
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| InChi Key |
JTVWJXUGGJTGDA-IBGZPJMESA-N
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| InChi Code |
InChI=1S/C24H19Cl3N2O4/c1-13-4-2-5-16(25)20(13)22(30)29-19(24(32)33)12-14-8-10-15(11-9-14)28-23(31)21-17(26)6-3-7-18(21)27/h2-11,19H,12H2,1H3,(H,28,31)(H,29,30)(H,32,33)/t19-/m0/s1
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| Chemical Name |
(2S)-2-[(2-chloro-6-methylbenzoyl)amino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoic acid
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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) |
DMSO : 12.5 mg/mL (24.71 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.47 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 12.5 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: ≥ 1.25 mg/mL (2.47 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 12.5 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: ≥ 1.25 mg/mL (2.47 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 | 1.9771 mL | 9.8857 mL | 19.7714 mL | |
| 5 mM | 0.3954 mL | 1.9771 mL | 3.9543 mL | |
| 10 mM | 0.1977 mL | 0.9886 mL | 1.9771 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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