| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T22655 | ||||
| Target Name | Mucosal addressin cell adhesion molecule 1 | ||||
| Target Type | Clinical Trial |
||||
| Drug Potency against Target | PF-00547659 | Drug Info | IC50 = 37 ng/mL | [552931] | |
| Action against Disease Model | PF-00547659 | MECA-367 and PF-00547659 (an anti-h uMan MAdCAM monoclonal antibody) bound with high affinity to mouse and h uMan MAdCAM with K(d) values of 5.1 and 16.1 pmol.L(-1) respectivelyand blocked the adhesion of alpha(4)beta(7) (+) leukocytes to MAdCAM with similar potency. MECA-367 and PF-00547659 induced a similar, dose-dependent two- to threefold increase in circulating populations of beta(7) (+) memory T-cells in the mouse and macaque; without affecting the beta(7) (-) populations. | [552931] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | In MAdCAM-1-deficient mice ( MAdCAM(Delta) )mice, the size of Peyer's patches was drastically reduced, compared with that of wild-type mice; this difference was detectable by 3 days after birth, indicating that MAdCAM-1 is dispensable for embryonic Peyer's patch development but mediates recruitment of lymphocytes into this lymphoid organ at later stages. Moreover, antigen-specific, IgA-positive PC were severely compromised in their migration to the small intestine; accordingly, there was a reduced n uMber of IgA-secreting PC in the lamina propria of the small intestine. The MAdCAM(Delta) mice were unable to mount a normal intestinal IgA response after oral immunization with cholera toxin.These data provide in vivo evidence that MAdCAM-1 is required for the localization and function of IgA-secreting PC in the intestine | [552931] | |||
| References | |||||
| Ref 552931 | Pharmacological characterization of PF-00547659, an anti-human MAdCAM monoclonal antibody. Br J Pharmacol. 2009 May;157(2):281-93. doi: 10.1111/j.1476-5381.2009.00137.x. Epub 2009 Apr 2. | ||||
| Ref 552931 | Pharmacological characterization of PF-00547659, an anti-human MAdCAM monoclonal antibody. Br J Pharmacol. 2009 May;157(2):281-93. doi: 10.1111/j.1476-5381.2009.00137.x. Epub 2009 Apr 2. | ||||
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