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Asunaprevir (BMS-650032)

现货
Catalog No.
A3195
NS3蛋白酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 3,620.00
现货
5mg
¥ 2,310.00
现货
10mg
¥ 3,990.00
现货
50mg
¥ 8,710.00
现货

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Background

Asunaprevir is an orally efficacious inhibitor of NS3 protease with IC50 value of 1nM [1].

Asunaprevir is an inhibitor of hepatitis C virus (HCV) NS3 protease. It can inhibit 6 major genotypes of HCV NS3/4A protease with IC50 values of 0.7nM, 0.3nM, 15nM, 78nM, 320nM, 1.6nM, 1.7nM and 0.9nM, respectively for genotype 1a, 1b, 2a, 2b, 3a, 4a, 5a and 6a, respectively. When using the purified recombinant full-length HCV NS3/4A protease complexes, asunaprevir shows the Ki values of 0.4nM and 0.2nM, respectively for genotype 1a and genotype 1b. The mechanism of the inhibition is that the acylsulfonamide of asunaprevir interacts with the catalytic site of NS3 protease in a noncovalent manner. Asunaprevir inhibits HCV RNA replication in different cell lines, including liver, T lymphocytes, lung, cervix, and embryonic kidney. It shows no obvious activity against other RNA viruses. The permeability of asunaprevir is similar to the compound with good absorption in humans. The tests of metabolism rate show that asunaprevir exhibits low to intermediate metabolic clearance. Plasma and tissue exposures in vivo indicate that asunaprevir displays a hepatotropic disposition [2].

References:
[1] Scola PM, Sun LQ, Wang AX, Chen J, Sin N, Venables BL, Sit SY, Chen Y, Cocuzza A, Bilder DM, D'Andrea SV, Zheng B, Hewawasam P, Tu Y, Friborg J, Falk P, Hernandez D, Levine S, Chen C, Yu F, Sheaffer AK, Zhai G, Barry D, Knipe JO, Han YH, Schartman R, Donoso M, Mosure K, Sinz MW, Zvyaga T, Good AC, Rajamani R, Kish K, Tredup J, Klei HE, Gao Q, Mueller L, Colonno RJ, Grasela DM, Adams SP, Loy J, Levesque PC, Sun H, Shi H, Sun L, Warner W, Li D, Zhu J, Meanwell NA, McPhee F. The discovery of asunaprevir (BMS-650032), an orally efficacious NS3 protease inhibitor for the treatment of hepatitis C virus infection. J Med Chem. 2014 Mar 13;57(5):1730-52.
[2] McPhee F, Sheaffer AK, Friborg J, Hernandez D, Falk P, Zhai G, Levine S, Chaniewski S, Yu F, Barry D, Chen C, Lee MS, Mosure K, Sun LQ, Sinz M, Meanwell NA, Colonno RJ, Knipe J, Scola P. Preclinical Profile and Characterization of the Hepatitis C Virus NS3 Protease Inhibitor Asunaprevir (BMS-650032). Antimicrob Agents Chemother. 2012 Oct;56(10):5387-96.

文献引用

1. Rago F, DiMare MT, et al. "Degron mediated BRM/SMARCA2 depletion uncovers novel combination partners for treatment of BRG1/SMARCA4-mutant cancers." Biochem Biophys Res Commun. 2019 Jan 1;508(1):109-116. PMID:30527810
2. Nadia Hegarat, Adrijana Crncec, et al. "Cyclin A triggers Mitosis either via Greatwall or Cyclin B." bioRxiv. 2018 December 19.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt748.29
Cas No.630420-16-5
FormulaC35H46ClN5O9S
SynonymsBMS-650032;BMS 650032;BMS650032,Asunaprevir
Solubility≥37.4145 mg/mL in DMSO, ≥48.6 mg/mL in EtOH, <2.51 mg/mL in H2O
Chemical Nametert-butyl N-[(2S)-1-[(2S,4R)-4-(7-chloro-4-methoxyisoquinolin-1-yl)oxy-2-[[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate
SDFDownload SDF
Canonical SMILESCC(C)(C)C(C(=O)N1CC(CC1C(=O)NC2(CC2C=C)C(=O)NS(=O)(=O)C3CC3)OC4=NC=C(C5=C4C=C(C=C5)Cl)OC)NC(=O)OC(C)(C)C
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

丙型肝炎病毒(HCV)NS3/4A蛋白酶基因型测定

使用已建立的方法(用于构建、表达以及纯化代表HCV基因型1a(H77c)和1b(J4L6S)的重组全长NS3/4A复合物)合成含6种主要HCV基因型(HC-J6、HC-J8、S52、ED43、SA13和HK-6A)的同源全长NS3/4A蛋白酶复合物。使用荧光共振能量转移(FRET)测定法评估纯化重组NS3/4A蛋白酶复合物的敏感性。计算IC50值。

细胞实验 [1]:

细胞系

HuH-7、MRC5、MT-2、HepG2、HeLa和HEK293细胞

制备方法

溶于DMSO。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

4天

实验结果

在各种细胞系中,包括肝、T淋巴细胞、肺、子宫颈以及胚胎肾细胞,Asunaprevir抑制HCV RNA复制。Asunaprevir对其它RNA病毒无明显活性。

动物实验 [2]:

动物模型

大鼠

给药剂量

10 μM;口服给药;60分钟

实验结果

在大鼠中,口服给予Asunaprevir具有适度的口服生物利用度以及1.0 μM·h的血浆AUC。然而,在口服给药后的第24小时,Asunaprevir的肝脏水平较高(15.2 μM),上述结果表明Asunaprevir于体内多分布于肝脏。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. McPhee F, Sheaffer AK, Friborg J, Hernandez D, Falk P, Zhai G, Levine S, Chaniewski S, Yu F, Barry D, Chen C, Lee MS, Mosure K, Sun LQ, Sinz M, Meanwell NA, Colonno RJ, Knipe J, Scola P. Preclinical Profile and Characterization of the Hepatitis C Virus NS3 Protease Inhibitor Asunaprevir (BMS-650032). Antimicrob Agents Chemother. 2012 Oct;56(10):5387-96.

[2]. Scola PM, Sun LQ, Wang AX, Chen J, Sin N, Venables BL, Sit SY, Chen Y, Cocuzza A, Bilder DM, D'Andrea SV, Zheng B, Hewawasam P, Tu Y, Friborg J, Falk P, Hernandez D, Levine S, Chen C, Yu F, Sheaffer AK, Zhai G, Barry D, Knipe JO, Han YH, Schartman R, Donoso M, Mosure K, Sinz MW, Zvyaga T, Good AC, Rajamani R, Kish K, Tredup J, Klei HE, Gao Q, Mueller L, Colonno RJ, Grasela DM, Adams SP, Loy J, Levesque PC, Sun H, Shi H, Sun L, Warner W, Li D, Zhu J, Meanwell NA, McPhee F. The discovery of asunaprevir (BMS-650032), an orally efficacious NS3 protease inhibitor for the treatment of hepatitis C virus infection. J Med Chem. 2014 Mar 13;57(5):1730-52.

质量控制

化学结构

Asunaprevir (BMS-650032)

相关生物数据

Asunaprevir (BMS-650032)

相关生物数据

Asunaprevir (BMS-650032)