GW559090 is a potent, selective, competitive and high-affinity α4β1 integrin (VLA-4) antagonist with Kd of 0.19/1.04 nM for huamn/rat α4β1, respectively.
GW559090 inhibits J6 cell adhesion to VCAM-1 in a monophasic fashion with a mean IC50 of 7.72 nM (2.39-24.9 nM), inhibits RPMI 8866 cell adhesion to MAdCAM with an IC50 of 23.0 nM, inhibits RPMI 8866 binding to VCAM-1, and CS-1 in a simple monophasic manner with respective IC50s of 4.81 nM and 24.5 nM.
GW559090 displays no significant inhibition on 53 receptors and 4 transporters in an MDS Pharma screen, including LFA-1.
GW559090 (topical treatment, 30 mg/mL) dose-dependently prevents desiccation-induced corneal barrier disruption, decreases dendritic cell activation in lymph nodes. reduces corneal expression of IL-1α, matrix metalloproteinase (MMP)-9, chemokine ligand 9 (CXCL9), and TGF-β1.
GW559090 acts primarily locally, not systemically, to improve DS-induced corneal barrier disruption.