RO0270608

• CAT Number: I044619
• CAS Number: 220846-33-3
• Molecular Formula: C24H19Cl3N2O4
• Molecular Weight: 505.78
• Purity: ≥95%
• Synonyms: (2S)-2-[(2-chloro-6-methylbenzoyl)amino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoic acid
• InChI: 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
• InChIKey: JTVWJXUGGJTGDA-IBGZPJMESA-N
• SMILES: CC1=C(C(=CC=C1)Cl)C(=O)NC(CC2=CC=C(C=C2)NC(=O)C3=C(C=CC=C3Cl)Cl)C(=O)O

RO0270608, the active metabolite of R411, is a dual alpha4beta1-alpha4beta7 (α4β1/α4β7) integrin antagonist. Antiinflammatory activity[1][2].
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 (IC50=30 nM)[2].
In a murine OVA-model of airway inflammation, RO0270608 i.n. abolishes allergen-induced inflammatory cell accumulation[2]

Reference

[1]. Hijazi Y, et al. Pharmacokinetics, safety, and tolerability of R411, a dual alpha4beta1-alpha4beta7 integrin antagonist after oral administration at single and multiple once-daily ascending doses in healthy volunteers. J Clin Pharmacol. 2004;44(12):1368-1
 [Content Brief]

[2]. M. Renzetti, et al. Dual α4/β1–α4/β7 vs α4/β1 selective antagonism is required for attenuation of allergic inflammatory responses. Journal of Allergy and Clinical Immunology. Volume 113, Issue 2, Supplement, February 2004, Page S221.