| Description | TAK-220 is a selective and orally bioavailable CCR5 antagonist (IC50s: 3.5 nM and 1.4 nM for inhibition on the binding of RANTES and MIP-1α to CCR5, respectively). |
| In vitro | 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]. |
| Target activity | HIV-1 (HTN):0.93 nM （EC50）（in PBMCs), HIV-1 (KK):1.2 nM （EC50）（in PBMCs), HIV-1 (KK):12 nM （EC90）（in PBMCs), MIP-1α-CCR5:1.4 nM （in CHO cells), HIV-1 (HHA):4 nM （EC90）（in PBMCs), HIV-1 (HKW):1.7 nM （EC50）（in PBMCs), HIV-1 (HKW):12 nM （EC90）（in PBMCs), HIV-1 (HNK):1.7 nM （EC50）（in PBMCs), HIV-1 (HTN):15 nM （EC90）（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 (HNK):28 nM （EC90）（in PBMCs), HIV-1 (HHA):0.55 nM （EC50）（in PBMCs) |
| molecular weight | 553.14 |
| Molecular formula | C31H41ClN4O3 |
| CAS | 333994-00-6 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 50 mg/mL (90.39 mM) |
| References | 1. Takashima K, et al. Highly potent inhibition of human immunodeficiency virus type 1 replication by TAK-220, an orally bioavailable small-molecule CCR5 antagonist. Antimicrob Agents Chemother. 2005 Aug;49(8):3474-82. 2. Tremblay CL, et al. TAK-220, a novel small-molecule CCR5 antagonist, has favorable anti-human immunodeficiency virus interactions with other antiretrovirals in vitro. Antimicrob Agents Chemother. 2005 Aug;49(8):3483-5. |