YU241279

YU241279 is an orally active inhibitor of CXCR5. It blocks the CXCL13-mediated Gαq-dependent calcium influx and the Gαi2-dependent cAMP reduction in cells expressing CXCR5. Additionally, YU241279 inhibits the proliferation of lymphoma cells expressing CXCR5 and reduces tumor burden in peripheral blood and bone marrow of mice with implanted lymphoma tissues. It is well-tolerated in mice, maintains stable plasma concentration, and shows no metabolic changes upon oral administration. YU241279 is applicable for research in angioimmunoblastic T-cell lymphoma and Burkitt B-cell lymphoma.

YU241279 (compound 2) is a potent inhibitor of CXCR5-mediated responses in HEK-293 cells expressing this receptor. It effectively suppresses the Gaq-mediated Ca²⁺ influx with an IC₅₀ of 166.4 nM in HBSS buffer and 444.4 nM in HBSS buffer with 1% BSA. Additionally, YU241279 inhibits Gαi2-mediated cAMP reduction with an IC₅₀ of 341.1 nM in HBSS buffer and 584.5 nM in HBSS buffer with 1% BSA. Furthermore, it demonstrates dose-dependent suppression of proliferation in CXCR5-expressing Raji Burkitt's B cell lymphoma cells, with significant inhibitory effects observed at concentrations as low as 1 μM over a 7-day period.

YU241279 (compound 2) administered at 40 mg/kg via oral gavage twice a day for 42 consecutive days significantly reduces AITL tumor burden in NSG mice.