TAK-220

TAK-220 is a selective and orally bioavailable CCR5 antagonist, with IC₅₀s of 3.5 nM and 1.4 nM for inhibition on the binding of RANTES and MIP-1α to CCR5, respectively, but shows no effect on the binding to CCR1, CCR2b, CCR3, CCR4, or CCR7; 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. IC50 & Target: IC50: 3.5 nM (RANTES-CCR5, in CHO cells), 1.4 nM (MIP-1α-CCR5, in CHO cells)^[1]
EC50: 1.2 nM (HIV-1 KK, in PBMCs), 0.72 nM (HIV-1 CTV, in PBMCs), 1.7 nM (HIV-1 HKW, in PBMCs), 1.7 nM (HIV-1 HNK, in PBMCs), 0.93 nM (HIV-1 HTN, in PBMCs), 0.55 nM (HIV-1 HHA, in PBMCs)^[1]
EC90: 12 nM (HIV-1 KK, in PBMCs), 5 nM (HIV-1 CTV, in PBMCs), 12 nM (HIV-1 HKW, in PBMCs), 28 nM (HIV-1 HNK, in PBMCs), 15 nM (HIV-1 HTN, in PBMCs), 4 nM (HIV-1 HHA, in PBMCs)^[1] In Vitro: TAK-220 is a selective CCR5 antagonist, with IC₅₀s of 3.5 nM and 1.4 nM for inhibition on the binding of RANTES and MIP-1α to CCR5 in CHO cells, respectively, but shows no effect on the binding to CCR1, CCR2b, CCR3, CCR4, or CCR7. TAK-220 (0-1000 nM) interacts with CCR5 but not with RANTES and inhibits the CCR5-mediated Casup>2+ signaling. TAK-220 inhibits R5 HIV-1 (JR-FL) envelope-mediated membrane fusion, with an IC₅₀ value of 0.42 nM, but does not alter X4 HIV-1 (HXB2) envelope-mediated membrane fusion. 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]. 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^[2].