TAK-779 是一种有效的，选择性的，非肽类 CCR5 和 CXCR3 拮抗剂，对 CCR5 的 Ki 值为 1.1 nM，同时可以有效地，选择性地抑制 R5 HIV-1，在 MAGI-CCR5 细胞中，EC50 和 EC90 值分别为 1.2 nM 和 5.7 nM。
|
MIP-1α-CCR5
1 nM (IC
50
, in CHO/CCR5 cells)
|
MIP-1β-CCR5
1 nM (IC
50
, in CHO/CCR5 cells)
|
RANTES-CCR5
1.4 nM (IC
50
, in CHO/CCR5 cells)
|
MCP-1-CCR2b
27 nM (IC
50
, in CHO/CCR5 cells)
|
R5 HIV-1 (Ba-L)
1.2 nM (EC
50
, in MAGI-CCR5 cells)
|
R5 HIV-1 (Ba-L)
5.7 nM (EC90, in MAGI-CCR5 cells)
|
R5 HIV-1 (Ba-L)
3.7 nM (EC
50
, in PBMCs)
|
R5 HIV-1 (Ba-L)
12.8 nM (EC90, in PBMCs)
|
R5 HIV-1 (KK)
1.6 nM (EC
50
, in PBMCs)
|
R5 HIV-1 (KK)
20.8 nM (EC90, in PBMCs)
|
R5 HIV-1 (HHA)
3.2 nM (EC
50
, in PBMCs)
|
R5 HIV-1 (HHA)
7.5 nM (EC90, in PBMCs)
|
R5 HIV-1 (CTV)
3.5 nM (EC
50
, in PBMCs)
|
R5 HIV-1 (CTV)
27 nM (EC90, in PBMCs)
|
mCXCR3
369 nM (IC
50
, in PBMCs)
|
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 EC
50
and EC
90
of 1.2 nM and 5.7 nM, respectively, in MAGI-CCR5 cells. TAK-779 less potently blocks the binding of [
125
I]-monocyte chemotactic protein 1 to CCR2b in CHO/CCR2b cells, with an IC
50
for CCR2b of 27 nM. TAK-779 also completely inhibits the binding of [
125
I]-RANTES to CHO/CCR5 cells with an IC
50
of 1.4 nM. TAK-779 (20 nM) selectively inhibits CCR5-mediated Ca
2+
-signaling. In addition, TAK-779 shows no inhibition on X4 HIV-1 strains. TAK-779 is an antagonist of CXCR3, and inhibits the migration of T cells but not T cell proliferation.