切换导航

Daclatasvir (BMS-790052)

现货
Catalog No.
A5618
HCV NS5A抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,800.00
现货
5mg
¥ 1,190.00
现货
25mg
¥ 3,480.00
现货
100mg
¥ 9,720.00
Ship with 10-15 days

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

Daclatasvir, formerly known as BMS-790052, is a potent NS5A inhibitor with EC50 values varying from 9 to 146 pM. [1,2]
The nonstructural 5A (NS5A) is a target in HCV drug development, which is a 447 amino-acid, zinc-binding phosphoprotein who plays an essential but enigmatic role in the virus life cycle. However the function of NS5A has no enzymatic activities, which makes it very difficult to understand the antiviral function of daclatasvir. It is assumed that Daclatasvir may interfere with the dimeric structure of NS5A, effecting subtle structural distortions that interfere with protein function in a specific way.[1,2]
The antiviral activity of daclatasvir towards genotypes was assessed by using replication-competent 1a or 1b replicons to construct hybrids in which the entire NS5A coding region or the first 100 amino acids of NS5A from different genotypes replaced the corresponding sequence of the parent replicon. Daclatasvir was reported to be highly potent across all HCV genotypes with half-maximum effective concentrations (EC50) ranging from 9 to 146 pM.[2]
A phase I clinical study showed Daclatasvir’s inhibition for HCV viruses. A 1 mg dose of daclatasvir produced a mean 1.8 log10 reduction in serum HCV RNA 24 h after administration. The 10 and 100 mg doses produced 3.2 log10 and 3.3 log10 reductions, respectively. Data collected from clinical trials on daclatasvir illustrated an initial, rapid viral decline followed by a slower fall in HCV RNA, which indicated that by inhibiting NS5A, daclatasvir blocks intracellular HCV RNA synthesis and virion assembly and secretion.[1]
References:
1.Herbst D A, Reddy K R. NS5A inhibitor, daclatasvir, for the treatment of chronic hepatitis C virus infection[J]. Expert opinion on investigational drugs, 2013, 22(10): 1337-1346.
2.Gao M, Nettles R E, Belema M, et al. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect[J]. Nature, 2010, 465(7294): 96-100.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt738.88
Cas No.1009119-64-5; 1214735-16-6
FormulaC40H50N8O6
Solubility≥36.6mg/mL in DMSO, ≥23.33 mg/mL in EtOH with ultrasonic, <2.44 mg/mL in H2O
Chemical Namemethyl N-[(2S)-1-[(2S)-2-[5-[4-[4-[2-[(2S)-1-[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]pyrrolidin-2-yl]-1H-imidazol-5-yl]phenyl]phenyl]-1H-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
SDFDownload SDF
Canonical SMILESCC(C)C(C(=O)N1CCCC1C2=NC=C(N2)C3=CC=C(C=C3)C4=CC=C(C=C4)C5=CN=C(N5)C6CCCN6C(=O)C(C(C)C)NC(=O)OC)NC(=O)OC
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

细胞实验 [1]:

细胞系

HCV基因型和JFH-1基因型2a感染性病毒

溶解方法

该化合物在DMSO中的溶解度大于36.6 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

EC50: 9-146 pM

应用

在细胞培养物中表达广泛的HCV基因型和JFH-1基因型2a感染性病毒的复制子中,BMS-790052显示皮摩尔的半数最大有效浓度,EC50值范围为9-146 pM。在Huh-7、HeLa和HEK293T细胞中,BMS-790052显示出相似的效力。

动物实验 [1]:

动物模型

长期感染HCV的患者

给药剂量

口服,10-100 mg

应用

在HCV感染的受试者中,单次口服剂量高达100 mg的BMS-790052安全且耐受性良好。在HCV感染的受试者中,BMS-790052具有10至14小时的平均血浆消除半衰期。单次施用100 mg剂量的BMS-790052,服药后24小时测定的平均病毒载量降低3.3log10,在两个感染基因型1b病毒的患者中额外持续120小时。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Gao M, Nettles R E, Belema M, et al. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect[J]. Nature, 2010, 465(7294): 96.

生物活性

Description Daclatasvir(BMS-790052; EBP 883)是HCV NS5A的高选择性的口服抑制剂,EC50值为9-50 pM。
靶点 HCV NS5A          
IC50 9 pM-50 pM(EC50)          

质量控制

质量控制和MSDS

批次:

化学结构

Daclatasvir (BMS-790052)