Table 1.
Pharmacological characterization of PF-00547659 in comparison with MECA-367
PF-00547659 | MECA-367 | |
---|---|---|
Antibody type | Human IgG2 kappa class | Rat IgG2a kappa class |
Reactivity | Human and cynomolgus MAdCAM | Mouse MAdCAM |
BIAcore binding to MAdCAM | hMAdCAM-IgG1 Fc fusion KD 16.1 pmol·L−1 (n = 5, CI = 7, 37.2) | mMAdCAM-IgG1 Fc fusion KD 5.1 pmol·L−1 (n = 2) |
Inhibition of CHO-hMAdCAM binding to JY cells | IC50, 0.457 µg·mL−1 (n = 34; 95% CI = 0.405, 0.516). | N.D. |
Inhibition of CHO-cynoMAdCAM to JY cells | IC50, 0.651 µg·mL−1 (n = 18, 95% CI = 0.566, 0.748) | N.D. |
Inhibition of MAdCAM-IgG1 Fc fusion protein to JY cells | hMAdCAM-IgG1 Fc fusion IC50, 0.037 µg·mL−1 (n = 32; 95% CI = 0.027, 0.052) | mMAdCAM-IgG1 Fc fusion IC50, 0.033 µg·mL−1 (n = 4; 95% CI = 0.021, 0.05) |
Inhibition of fibronectin and VCAM binding to Jurkat T-cells | IC50, >24.5 µg·mL−1 | N.D. |
MAdCAM, mucosal addressin cell adhesion molecule; N.D., not determined; VCAM, vascular cell adhesion molecule.