PSI-7409 tetrasodium
目录号 : GC33946
PSI-7409tetrasodium是一种sofosbuvir(PSI-7977)的5'-三磷酸活性代谢物，能够抑制HCVNS5Bpolymerases，对GT1b_Con1，GT2a_JFH1，GT3a和GT4aNS5B聚合酶的IC50值分别为1.6，2.8，0.7和2.6μM。
Cas No.:1621884-22-7
Sample solution is provided at 25 µL, 10mM.
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PSI-7409 tetrasodium is an active 5'-triphosphate metabolite of sofosbuvir (PSI-7977), inhibiting HCV NS5B polymerases, with IC50s of 1.6, 2.8, 0.7 and 2.6 μM for GT 1b_Con1, GT 2a_JFH1, GT 3a, and GT 4a NS5B polymerases, respectively.
PSI-7409 tetrasodium is an active 5'-triphosphate metabolite, inhibiting HCV NS5B polymerases, with IC50s of 1.6, 2.8, 0.7 and 2.6 μM for GT 1b_Con1, GT 2a_JFH1, GT 3a, and GT 4a NS5B polymerases, respectively. PSI-7409 also weakly inhibits human DNA polymerase α, with an IC50 of 550 μM, but shows no inhibition on DNA Pol β and γ[1]. In clone A cells, the levels of PSI-7409 gradually increases to a maximum concentration of about 25 μM over a period of 48 h. PSI-7409 forms at a much faster rate in primary human hepatocytes, achieving a maximum intracellular concentration of ∼100 μM at 4 h and remains at that concentration for 48 h[2].
[1]. Lam AM, et al. PSI-7851, a pronucleotide of beta-D-2'-deoxy-2'-fluoro-2'-C-methyluridine monophosphate, is a potent and pan-genotype inhibitor of hepatitis C virus replication. Antimicrob Agents Chemother. 2010 Aug;54(8):3187-96. [2]. Murakami E, et al. Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47.
Kinase experiment: | Human DNA polymerase α, β, or γ is assayed in a 10-μL reaction mixture containing 50 mM Tris (pH 7.5), 50 mM NaCl, 3 mU/μL activated calf thymus DNA, a 20 μM concentration of all four natural deoxynucleoside triphosphates, 4 μCi [α-32P]dCTP, 5 mM MgCl2, and increasing concentrations of PSI-7409 (up to 1 mM), D-ddFCTP, or aphidicolin. DNA polymerase α, β, or γ is added to the reaction mixture to give final concentrations of 20, 18, and, 50 μg/mL, respectively. All reactions are run at 37°C and quenched at 30 min by mixing with 1 μL of 0.5 M EDTA. The radiolabeled products are quantified. A nonlinear fit is performed to determine the IC50. The activity of RNA polymerase II is determined in a 25-μL in vitro transcription reaction mixture containing 100 ng of cytomegalovirus (CMV) immediate-early promoter DNA, 400 μM ATP, CTP, and UTP, 16 μM GTP, 10 μCi [α-32P]GTP, 3 mM MgCl2, and various concentrations of PSI-7409 (up to 1 mM), 3'-dCTP, or α-amanitin in transcription buffer (20 mM HEPES [pH 7.9], 100 mM KCl, 0.2 mM EDTA, 0.5 mM DTT, and 20% glycerol). All reactions are run at 30°C and quenched at 60 min by mixing with 125 μL of stop solution (0.3 M Tris-HCl [pH 7.4], 0.3 M sodium acetate, 0.5% SDS, 2 mM EDTA, and 3 μg/mL tRNA). The RNA product is purified. The resulting samples contains 12 μL and the same volume of gel loading dye (98% formamide, 10 mM EDTA, 0.1% xylene cyanol, and 0.1% bromophenol blue) is added. The samples are heated at 90°C for 5 min and loaded onto a 6% polyacrylamide sequencing gel. After running, the gel is exposed to a phosphorscreen, and the product is visualized and quantified by using a phosphorimager[1]. |
References: [1]. Lam AM, et al. PSI-7851, a pronucleotide of beta-D-2'-deoxy-2'-fluoro-2'-C-methyluridine monophosphate, is a potent and pan-genotype inhibitor of hepatitis C virus replication. Antimicrob Agents Chemother. 2010 Aug;54(8):3187-96. | |
| Cas No. | 1621884-22-7 | SDF | |
| Canonical SMILES | O[C@@H]([C@@](C)(F)[C@H](N1C(NC(C=C1)=O)=O)O2)[C@H]2COP(O)(OP(OP(O)(O)=O)(O)=O)=O.[4Na] | ||
| 分子式 | C10H16FN2Na4O14P3 | 分子量 | 592.12 |
| 溶解度 | Water : ≥ 125 mg/mL (211.11 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。 |
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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 | 1.6888 mL | 8.4442 mL | 16.8885 mL |
| 5 mM | 0.3378 mL | 1.6888 mL | 3.3777 mL |
| 10 mM | 0.1689 mL | 0.8444 mL | 1.6888 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