Vercirnon (GSK1605786A) sodium is an orally bioavailable, selective, and potent CCR9 antagonist. It inhibits CCR9-mediated calcium mobilization and chemotaxis in Molt-4 cells with IC50 values of 5.4 nM and 3.4 nM, respectively. Vercirnon sodium demonstrates high selectivity, showing IC50 values exceeding 10 µM for CCR1-12 and CX3CR1-7 receptors. It also inhibits CCL25-directed chemotaxis in both CCR9 splice variants, CCR9A and CCR9B, with IC50 values of 2.8 nM and 2.6 nM, respectively.

CCR9:10 nM (IC50)

Vercirnon (GSK-1605786) sodium effectively suppresses the movement of primary cells expressing CCR9 towards CCL25, demonstrating an inhibition concentration (IC 50) of 6.8 nM. It also significantly blocks the CCL25-induced migration of retinoic acid (RA)-cultured human T cells. In the presence of 100% human AB serum, Vercirnon sodium impedes the chemotaxis mediated by CCL25 in RA-cultured cells, achieving an IC 50 of 141 nM. Moreover, it is a highly efficient inhibitor against the migration of mouse and rat thymocytes triggered by CCL25, with IC 50 values of 6.9 nM and 1.3 nM, respectively[1].

Vercirnon (GSK1605786A) sodium administered subcutaneously at doses of 10 and 50 mg/kg, twice per day from 2 to 12 weeks of age, effectively reduces the severity of intestinal inflammation in the TNFΔARE mouse model (C57BL/6 mice with terminal ileitis)[1]. At a dose of 50 mg/kg, it resulted in complete protection against severe inflammation caused by TNF- overexpression, with a similar protective effect observed at the lower dose.