α4β1 4 nM (IC 50 ) α4β7 2 μM (IC 50 ) α1β1 >100 μM (IC 50 ) α5β1 >100 μM (IC 50 ) α6β1 >100 μM (IC 50 ) αLβ2 >100 μM (IC 50 ) αIIbβ3 >100 μM (IC 50 )

BIO-1211 (5 and 10 mg/kg, orally, once every other day) results in reduced cytokines expression, leukocyte trafficking, and inhibition of inflammatory responses in EAE in a dose-independent manner. BIO-1211 exhibits a considerable depletion in the EAE clinical score, which correlated with decreased expression of TNF-α, IL-17, IFN-γ and pervade of CD11b+ and CD45+ cells into the cerebral cortex. Animal Model: Naive, C57BL/6 mice (male, 8 weeks old, 20-25 g weight). Dosage: 5 and 10 mg/kg. Administration: Orally once every other day starting the day before immunization until day 21 post-immunization. Result: Could prevent the induction of EAE. Significantly delayed the onset of EAE and reduced the severity of clinical EAE compared to the vehicle group. Markedly reduced the expression of both CD11b and CD45 in comparison with the vehicle group. mRNA and soluble form of a subset of target inflammatory cytokines (IFNγ, IL-17, and TNF-α) was dramatically decreased.

BIO-1211 是高度选择性的、具有口服活性的 α4β1 (VLA-4) 抑制剂，其对 α4β1 和 α4β7 的 IC50 值分别为 4 nM 和 2 μM。