333994-00-6
333994-00-6 結(jié)構(gòu)式
基本信息
TAK 220
TAK220
1-ACETYL-N-(3-(4-(4-CARBAMOYLBENZYL)PIPERIDIN-1-YL)PROPYL)-N-(3-CHLORO-4-METHYLPHENYL)PIPERIDINE-4-CARBOXAMIDE
4-Piperidinecarboxamide, 1-acetyl-N-[3-[4-[[4-(aminocarbonyl)phenyl]methyl]-1-piperidinyl]propyl]-N-(3-chloro-4-methylphenyl)-
物理化學性質(zhì)
常見問題列表
|
RANTES-CCR5 3.5 nM (IC 50 , in CHO cells) |
MIP-1α-CCR5 1.4 nM (IC 50 , in CHO cells) |
HIV-1 (KK) 1.2 nM (EC 50 , in PBMCs) |
HIV-1 (CTV) 0.72 nM (EC 50 , in PBMCs) |
HIV-1 (HKW) 1.7 nM (EC 50 , in PBMCs) |
HIV-1 (HNK) 1.7 nM (EC 50 , in PBMCs) |
HIV-1 (HTN) 0.93 nM (EC 50 , in PBMCs) |
HIV-1 (HHA) 0.55 nM (EC 50 , in PBMCs) |
HIV-1 (KK) 12 nM (EC90, in PBMCs) |
HIV-1 (CTV) 5 nM (EC90, in PBMCs) |
HIV-1 (HKW) 12 nM (EC90, in PBMCs) |
HIV-1 (HNK) 28 nM (EC90, in PBMCs) |
HIV-1 (HTN) 15 nM (EC90, in PBMCs) |
HIV-1 (HHA) 4 nM (EC90, in PBMCs) |
TAK-220 is a selective CCR5 antagonist, with IC 50 s 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 IC 50 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 EC 50 s 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 EC 90 s 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. TAK-220 shows potent inhibitory activity against the R5 isolates, with IC 50 s 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.