PF-07054894 is a potent, functionally selective CCR6 antagonist, blocks in vitro CCL20- dependent human T cell chemotaxis with IC50 of 5.7 nM.
PF-07054894 dispays negligible activity (<12% over basal activity) in an assay panel of 168 G protein-coupled receptors, with more than 30% inhibition of agonist-dependent activity on only 3 receptors: CCR6, CCR7, and CXCR2.
PF-07054894 displays >50- and 150-fold functional selectivity relative to CCR7 and CXCR2.
PF-07054894 increased the frequency of CCR6+ peripheral blood T cells suggesting that blockade of CCR6 inhibited homeostatic migration of T cells from blood to tissues of naïve cynomolgus monkeys.
PF-07054894 caused an increase in cell surface CCR6 in mouse and monkey B cells which was recapitulated in mouse splenocytes in vitro.
