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]
[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):1368-1378.
[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.