ALS-8112
目录号 : GC32070
ALS-8112是高效，选择性的呼吸道合胞病毒（RSV）聚合酶抑制剂。5'-三磷酸形式的ALS-8112抑制RSV聚合酶，IC50值为0.02μM。
Cas No.:1445379-92-9
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
ALS-8112 is a potent and selective respiratory syncytial virus (RSV) polymerase inhibitor. The 5'-triphosphate form of ALS-8112 inhibits RSV polymerase with an IC50 of 0.02 μM.
The 5'-triphosphate form of ALS-8112 (ALS-8112-TP) is the active form of the drug and selectively inhibits RSV polymerase through chain termination of RNA synthesis[2]. ALS-008112 enters various types of epithelial cells in the respiratory tract and is subsequently phosphorylated to form an intracellular nucleoside triphosphate with a half-life of approximately 29 hours. The nucleoside triphosphate analogue inhibits RSV replication by means of chain termination[3]. ALS-8112 is a pan-strain inhibitor of RSV replication in vitro. The RNA transcription activity of the RSV-RNP complex is dose-proportionally inhibited by ALS-8112-TP with an IC50 of 0.020 ± 0.008 μM[4].
[1]. Wang G, et al. Discovery of 4'-chloromethyl-2'-deoxy-3',5'-di-O-isobutyryl-2'-fluorocytidine (ALS-8176), a first-in-class RSV polymerase inhibitor for treatment of human respiratory syncytial virus infection. J Med Chem. 2015 Feb 26;58(4):1862-78. [2]. Jordan PC, et al. Activation Pathway of a Nucleoside Analog Inhibiting Respiratory Syncytial Virus Polymerase. ACS Chem Biol. 2017 Jan 20;12(1):83-91. [3]. DeVincenzo JP, et al. Activity of Oral ALS-008176 in a Respiratory Syncytial Virus Challenge Study. N Engl J Med. 2015 Nov 19;373(21):2048-58. [4]. Deval J, et al. Molecular Basis for the Selective Inhibition of Respiratory Syncytial Virus RNA Polymerase by 2'-Fluoro-4'-Chloromethyl-Cytidine Triphosphate. PLoS Pathog. 2015 Jun 22;11(6):e1004995.
|
Cell experiment: |
ALS-8112 and its prodrug ALS-8176 are stored at 4°C in dimethyl sulfoxide (DMSO), and diluted in water. HEp-2 cells per well are plated in a 96-well plate. Each compound is serially diluted (1:3) up to 9 distinct concentrations. Cells are pre-incubated with compounds for 24 hours at 37°C in a 5% CO2 atmosphere. After 24 hours of pre-incubation with compounds, RSV A2, Long, or B1 at a multiplicity of infection (MOI) of 0.5 is added to the cells, except for the background controls. The plate is then incubated for additional 4 days in the same conditions and at the end of the incubation 50 μL the supernatant from each well of the plate is collected[4]. |
|
References: [1]. Wang G, et al. Discovery of 4'-chloromethyl-2'-deoxy-3',5'-di-O-isobutyryl-2'-fluorocytidine (ALS-8176), a first-in-class RSV polymerase inhibitor for treatment of human respiratory syncytial virus infection. J Med Chem. 2015 Feb 26;58(4):1862-78. |
|
| Cas No. | 1445379-92-9 | SDF | |
| Canonical SMILES | OC[C@]1(CCl)[C@@H](O)[C@@H](F)[C@H](N2C(N=C(N)C=C2)=O)O1 | ||
| 分子式 | C10H13ClFN3O4 | 分子量 | 293.68 |
| 溶解度 | DMSO : ≥ 47 mg/mL (160.04 mM) | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.4051 mL | 17.0253 mL | 34.0507 mL |
| 5 mM | 0.681 mL | 3.4051 mL | 6.8101 mL |
| 10 mM | 0.3405 mL | 1.7025 mL | 3.4051 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet