TAK-779 is a potent and selective nonpeptide antagonist of CCR5 and CXCR3, with a K_i of 1.1 nM for CCR5, and effectively and selectively inhibits R5 HIV-1, with EC₅₀ and EC₉₀ of 1.2 nM and 5.7 nM, respectively, in MAGI-CCR5 cells. IC50 & Target: Ki: 1.1 nM (CCR5)^[1]
EC50: 1.2 nM (R5 HIV-1, in MAGI-CCR5 cells)^[1]
EC90: 5.7 nM (R5 HIV-1, in MAGI-CCR5 cells)^[1]
CXCR^[2] In Vitro: TAK-779 is a potent and selective nonpeptide antagonist of CCR5, with a K_i of 1.1 nM, and effectively and selectively inhibits R5 HIV-1, with EC₅₀ and EC₉₀ of 1.2 nM and 5.7 nM, respectively, in MAGI-CCR5 cells. TAK-779 less potently blocks the binding of [¹²⁵I]-monocyte chemotactic protein 1 to CCR2b in CHO/CCR2b cells, with an IC₅₀ for CCR2b of 27 nM. TAK-779 also completely inhibits the binding of [¹²⁵I]-RANTES to CHO/CCR5 cells with an IC₅₀ of 1.4 nM. TAK-779 (20 nM) selectively inhibits CCR5-mediated Ca²⁺-signaling. In addition, TAK-779 shows no inhibition on X4 HIV-1 strains^[1]. TAK-779 is an antagonist of CXCR3, and inhibits the migration of T cells but not T cell proliferation^[2]. In Vivo: TAK-779 (10 mg/kg per day, s.c.) significantly prolongs the allograft survival of the rat intestinal transplantation model. TAK-779 also decreases the number of CD4⁺ as well as CD8⁺ T cells in spleen, blood and recipient mesenteric lymph nodes (MLN)^[2]. TAK-779 (150 µg per mouse, s.c.) supppresses the development of experimental autoimmune encephalomyelitis (EAE) in myelin oligodendrocyte glycoprotein (MOG)-immunized C57BL/6 mice. TAK-779 decreases the infiltration of CXCR3 and CCR5 bearing leukocytes into the spinal cord. TAK-779 does not alter myelin oligodendrocyte glycoprotein (MOG)-specific immune responses or affect the potential of MOG-specific T cells to transfer experimental autoimmune encephalomyelitis (EAE)^[3].