TAK-220 is a selective and orally bioavailable CCR5 antagonist with IC50 values of 3.5 nM for RANTES binding inhibition and 1.4 nM for MIP-1α binding inhibition to CCR5.

HIV-1 (HHA):0.55 nM （EC50）（in PBMCs), HIV-1 (HNK):28 nM （EC90）（in PBMCs), HIV-1 (HTN):15 nM （EC90）（in PBMCs), HIV-1 (HNK):1.7 nM （EC50）（in PBMCs), X4 HIV-1 (CTV):0.72 nM （EC50）（in PBMCs), X4 HIV-1 (CTV):5 nM （EC90）（in PBMCs), RANTES-CCR5:3.5 nM （in CHO cells), HIV-1 (HKW):1.7 nM （EC50）（in PBMCs), HIV-1 (HKW):12 nM （EC90）（in PBMCs), MIP-1α-CCR5:1.4 nM （in CHO cells), HIV-1 (HHA):4 nM （EC90）（in PBMCs), HIV-1 (KK):1.2 nM （EC50）（in PBMCs), HIV-1 (KK):12 nM （EC90）（in PBMCs), HIV-1 (HTN):0.93 nM （EC50）（in PBMCs)

TAK-220 inhibits R5 HIV-1 (JR-FL) envelope-mediated membrane fusion (IC50: 0.42 nM). TAK-220 shows potent inhibitory activity against the R5 isolates, with IC50s of 3.12 nM against HIV-1 R5-08, 13.47 nM against HIV-1 R5-06, and 2.26 nM against HIV-1 R5-18. TAK-220 (>100 nM) has no toxicity in uninfected PBMCs. TAK-220 (0-1000 nM) interacts with CCR5 but not with RANTES and inhibits the CCR5-mediated Casup>2+ signaling. TAK-220 also selectively inhibits HIV-1, with EC50s of 1.2 nM (HIV-1 KK), 0.72 nM (HIV-1 CTV), 1.7 nM (HIV-1 HKW), 1.7 nM (HIV-1 HNK), 0.93 nM (HIV-1 HTN), and 0.55 nM (HIV-1 HHA), and EC90s of 12 nM (HIV-1 KK), 5 nM (HIV-1 CTV), 12 nM (HIV-1 HKW), 28 nM (HIV-1 HNK), 15 nM (HIV-1 HTN), and 4 nM (HIV-1 HHA) in PBMCs [1][2].