333994-00-6

中文名称 TAK-220

英文名称 TAK-220

CAS 333994-00-6

分子式 C31H41ClN4O3

分子量 553.14

MOL 文件 333994-00-6.mol

333994-00-6 结构式

基本信息物理化学性质常见问题列表

基本信息

中文别名

化合物 T16973

英文别名

TAK-220
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)-

物理化学性质

熔点166-167 °C(Solv: ethyl acetate (141-78-6); ethanol (64-17-5))

沸点757.8±60.0 °C(Predicted)

密度1.208±0.06 g/cm3(Predicted)

储存条件-20°C储存

溶解度可溶于DMSO

酸度系数(pKa)16.16±0.50(Predicted)

形态结晶固体

颜色White to off-white

常见问题列表

生物活性

TAK-220 是一种选择性的，可口服的 CCR5 拮抗剂，能够抑制 RANTES，MIP-1α 与 CCR5 结合，IC50 值分别为 3.5 nM 和 1.4 nM，但是对 CCR1，CCR2b，CCR3，CCR4 或者 CCR7 无作用; TAK-220 也可选择性地抑制 HIV-1，在外周单核细胞中，EC50 值分别为 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) 和 0.55 nM (HIV-1 HHA)，EC90 值分别为 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) 及 4 nM (HIV-1 HHA)。

靶点

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)

体外研究

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.