Background:

Vercirnon (GSK-1605786) is an orally bioavailable, selective, and potent antagonist of CCR9, with an IC50 of 10 nM, used in the research of inflammatory bowel diseases.

Vercirnon (GSK-1605786) is an orally bioavailable, selective, and potent antagonist of human CCR9. Vercirnon inhibits CCL25-induced calcium mobilization with an IC50 value of 5.4 ± 0.7 nM. Vercirnon is also a potent inhibitor of CCL25-induced Molt-4 chemotaxis with an IC50 of 3.5 ± 0.3 nM. Vercirnon shows inhibitory activity against Molt-4 migration with an IC50 of 33.4 ± 1.3 nM in 100% human AB serum. Moreover, Vercirnon suppresses the binding of [3H] CCX807 to Molt-4 cells with an IC50 of 6 nM. Vercirnon inhibits the chemotaxis of Baf-3/CCR9A cells as well as Baf-3/CCR9A cells with IC50s of 2.8 ± 1.1 nM and 2.6 ± 0.7 nM, respectively. Vercirnon potently inhibits CCL25-induced chemotaxis with an IC50 value of 6.8 ± 1.7 nM in buffer, and exhibits inhibition on RA-cultured cell CCL25-medidated chemotaxis in 100% human AB serum with an IC50 of 141 ± 13 nM[1].

Vercirnon (GSK-1605786) (10, 50 mg/kg twice daily) protects from the severe inflammation associated with TNF-α overexpression in the TNFΔARE Mouse Model. Vercirnon (50?mg/kg c.c. twice daily) blocks the colitis-associated weight loss inherent in the mdr1a?/? model, and also abrogates growth arrest in the colitis mdr1a ?/? mice[2].

参考文献:
[1]. Walters MJ, et al. Characterization of CCX282-B, an orally bioavailable antagonist of the CCR9 chemokine receptor, for treatment of inflammatory bowel disease. J Pharmacol Exp Ther. 2010 Oct;335(1):61-9.
[2]. Bekker P, et al. CCR9 Antagonists in the Treatment of Ulcerative Colitis. Mediators Inflamm. 2015;2015:628340.
[3]. Zhang J, et al. Biarylsulfonamide CCR9 inhibitors for inflammatory bowel disease. Bioorg Med Chem Lett. 2015 Sep 1;25(17):3661-4.