Vercirnon is an orally bioavailable antagonist of chemokine receptor 9 (CCR9) with an IC50 value of 5.4 nM for inhibition of CCL25-induced calcium mobilization in Molt-4 cells.1 It is selective for CCR9 over CCR1-12 and CX3CR1-7 (IC50s = >10 ?M for all). It also inhibits CCL25-induced Molt-4 chemotaxis in 0.1% BSA/HBSS and in 100% human AB serum (IC50s = 3.5 and 33.4 nM, respectively), as well as chemotaxis of human T cells stimulated by retinoic acid (RA) and mouse and rat thymocytes. Vercirnon binds allosterically to the intracellular side of CCR9 and prevents G protein coupling.2
1.Walters, M.J., Wang, Y., Lai, N., et al.Characterization of CCX282-B, an orally bioavailable antagonist of the CCR9 chemokine receptor, for treatment of inflammatory bowel diseaseJ. Pharmacol. Exp. Ther.335(1)61-69(2010) 2.Oswald, C., Rappas, M., Kean, J., et al.Intracellular allosteric antagonism of the CCR9 receptorNature540(7633)462-465(2016)