ACH-806 (GS9132)
(Synonyms: GS9132) 目录号 : GC32305
ACH-806 (GS9132) 是一种 NS4A 拮抗剂，可抑制丙型肝炎病毒 (HCV) 复制，EC50 为 14 nM。
Cas No.:870142-71-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Huh-luc/neo cells are seeded in 96-well plates at a density of 8000 cells per well in a final volume of 200 μL of Dulbecco modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum. One day after seeding, ACH-806 is serially diluted in 100% dimethyl sulfoxide (DMSO) and added to cells at a 1:200 dilution, achieving a final concentration of 0.5% DMSO in a total volume of 200 μL. Cells are further incubated for 3 days (96 h post-seeding), and the inhibition of HCV replicon replication is quantified by measurement of luciferase activity using a commercial kit[1]. |
References: [1]. Yang W, et al. ACH-806, an NS4A antagonist, inhibits hepatitis C virus replication by altering the composition of viral replication complexes. Antimicrob Agents Chemother. 2013 Jul;57(7):3168-77. | |
ACH-806 is an NS4A antagonist which can inhibit Hepatitis C Virus (HCV) replication with an EC50 of 14 nM.
ACH-806 is an NS4A antagonist which can inhibit Hepatitis C Virus (HCV) replication with an EC50 of 14 nM. ACH-806 treatment results in significant reductions of both NS3 and NS4A in the transfected cells. This finding is reminiscent of ACH-806-treated replicon cells in which the amounts of NS3 and NS4A are also both decreased. The total amount of NS3 in the ACH-806-treated sample is reduced by ~6-fold (100/16) and causes a reduction of NS4A-bound NS3 ~29-fold (261/9). The levels of labeled NS3 and NS4A immunoprecipitated by anti-NS3 antibody are apparently reduced after the treatment of ACH-806. ACH-806 also induces significant decreases of NS3 and NS4A and promotes p14 formation in the parental replicon cells but not in the ACH-806-resistant replicon cells[1].
[1]. Yang W, et al. ACH-806, an NS4A antagonist, inhibits hepatitis C virus replication by altering the composition of viral replication complexes. Antimicrob Agents Chemother. 2013 Jul;57(7):3168-77.
| Cas No. | 870142-71-5 | SDF | |
| 别名 | GS9132 | ||
| Canonical SMILES | O=C(C1=CC=CN=C1)NC(NC2=CC=C(OCCCCC)C(C(F)(F)F)=C2)=S | ||
| 分子式 | C19H20F3N3O2S | 分子量 | 411.44 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4305 mL | 12.1524 mL | 24.3049 mL |
| 5 mM | 0.4861 mL | 2.4305 mL | 4.861 mL |
| 10 mM | 0.243 mL | 1.2152 mL | 2.4305 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
ACH-806, an NS4A antagonist, inhibits hepatitis C virus replication by altering the composition of viral replication complexes
Antimicrob Agents Chemother 2013 Jul;57(7):3168-77.PMID:23629709DOI:10.1128/AAC.02630-12.
Treatment of hepatitis C patients with direct-acting antiviral drugs involves the combination of multiple small-molecule inhibitors of distinctive mechanisms of action. ACH-806 (or GS-9132) is a novel, small-molecule inhibitor specific for hepatitis C virus (HCV). It inhibits viral RNA replication in HCV replicon cells and was active in genotype 1 HCV-infected patients in a proof-of-concept clinical trial (1). Here, we describe a potential mechanism of action (MoA) wherein ACH-806 alters viral replication complex (RC) composition and function. We found that ACH-806 did not affect HCV polyprotein translation and processing, the early events of the formation of HCV RC. Instead, ACH-806 triggered the formation of a homodimeric form of NS4A with a size of 14 kDa (p14) both in replicon cells and in Huh-7 cells where NS4A was expressed alone. p14 production was negatively regulated by NS3, and its appearance in turn was associated with reductions in NS3 and, especially, NS4A content in RCs due to their accelerated degradation. A previously described resistance substitution near the N terminus of NS3, where NS3 interacts with NS4A, attenuated the reduction of NS3 and NS4A conferred by ACH-806 treatment. Taken together, we show that the compositional changes in viral RCs are associated with the antiviral activity of ACH-806. Small molecules, including ACH-806, with this novel MoA hold promise for further development and provide unique tools for clarifying the functions of NS4A in HCV replication.
Selection of replicon variants resistant to ACH-806, a novel hepatitis C virus inhibitor with no cross-resistance to NS3 protease and NS5B polymerase inhibitors
Antimicrob Agents Chemother 2008 Jun;52(6):2043-52.PMID:18411324DOI:10.1128/AAC.01548-07.
We have discovered a novel class of compounds active against hepatitis C virus (HCV), using a surrogate cellular system, HCV replicon cells. The leading compound in the series, ACH-806 (GS-9132), is a potent and specific inhibitor of HCV. The selection of resistance replicon variants against ACH-806 was performed to map the mutations conferring resistance to ACH-806 and to determine cross-resistance profiles with other classes of HCV inhibitors. Several clones emerged after the addition of ACH-806 to HCV replicon cells at frequencies and durations similar to that observed with NS3 protease inhibitors and NS5B polymerase inhibitors. Phenotypic analyses of these clones revealed that they are resistant to ACH-806 but remain sensitive to other classes of HCV inhibitors. Moreover, no significant change in the susceptibility to ACH-806 was found when the replicon cellular clones resistant to NS3 protease inhibitors and NS5B polymerase inhibitors were examined. Sequencing of the entire coding region of ACH-806-resistant replicon variants yielded several consensus mutations. Reverse genetics identified two single mutations in NS3, a cysteine-to-serine mutation at amino acid 16 and an alanine-to-valine mutation at amino acid 39, that are responsible for the resistance of the replicon variants to ACH-806. Both mutations are located at the N terminus of NS3 where extensive interactions with the central hydrophobic region of NS4A exist. These data provide evidence that ACH-806 inhibits HCV replication by a novel mechanism.