齊多呋定作用機制 - Medchemexpress - MCE中國

1、Product Data SheetZidovudineCat. No.: HY-17413CAS No.: 30516-87-1分式: CHNO分量: 267.24作靶點: HIV; CRISPR/Cas9作通路: Anti-infection; Cell Cycle/DNA Damage儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 100 mg/mL (374.20 mM)* means soluble, but saturation unknown.Solven

2、tMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 3.7420 mL 18.7098 mL 37.4195 mL5 mM 0.7484 mL 3.7420 mL 7.4839 mL10 mM 0.3742 mL 1.8710 mL 3.7420 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍浮?/p>

3、以下溶解案都請先按照 In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (9.35 mM); Clear solution此案可獲得 2.5 mg/mL (9.35 mM，飽和度未知) 的澄清溶液。以 1 mL 作液

4、為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (9.35 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (9.35 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO

5、 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (9.35 mM); Clear solution此案可獲得 2.5 mg/mL (9.35 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Zidovudine率。種核苷逆轉(zhuǎn)錄酶抑制劑 (NRTI)，泛于治療 HIV感染。Z

6、idovudine 增強 CRISPR/Cas9調(diào)節(jié)的編輯頻IC & Target HIV-1 CRISPR/Cas9體外研究 Zidovudine inhibits SVG, Primary human fetal astrocytes (PFA), peripheral blood mononuclear cells (PBMC), andmonocyte-derived macrophages (MDM) with EC50 of 17, 1311, 8, and 5 nM, respectively. Zidovudine inhibits SVG,PFA, PBMC, and MDM

7、 with EC90 of 0.205 M, 44.157 M, 0.481 M, and 0.219 M, respectively1. Genome editing viaCRISPR/Cas9 has become an efficient and reliable way to make precise, targeted changes to the genome of livingcells. CXCR4 is a co-receptor for the human immunodeficiency virus type 1 (HIV-1) infection and has be

8、en consideredas an important therapeutic target for AIDS. CXCR4 mediates viral entry into human CD4+ cells by binding toenvelope protein, gp120. Human CXCR4 gene is efficiently disrupted by CRISPR/Cas9-mediated genome editing,leading to HIV-1 resistance of human primary CD4+ T cells. The Cas9-mediat

9、ed ablation of CXCR4 demonstrated highspecificity and negligible off-target effects without affecting cell division and propagation2.體內(nèi)研究 Intravitrous injection of the NRTIs Lamivudine (3TC), Zidovudine (AZT), or Abacavir (ABC) suppresses the laser-induced choroidal neovascularization (CNV) in wild-

10、type mice compared to PBS vehicle. The mean level of VEGF-A inthe RPE/choroid, which peaks on day 3 after laser injury, is significantly reduced in 3TC-, AZT- and ABC-treated eyescompared with control eyes in wild-type mice, but not inP2rx7-/- mice3.PROTOCOLCell Assay 1 Assays are performed in all c

11、ell types in the presence of titrating concentrations of ARV. 5,000 SVG, 2,500 PFA,200,000 PBMC, or 50,000 MDM cells/well are seeded into triplicate wells of 96-well plates. Twenty-four hours later,the culture medium is removed and replaced with medium containing the ARV or DMSO (0.5% vol/vol), ande

12、quivalent TCID50 infectious units of luciferase reporter virus are added to the cells. After a 16 h incubation at 37C,the initial viral inoculum is removed and replaced with culture medium containing the same antiretroviral drug (ARV)or DMSO (0.5% vol/vol) concentrations. At 72 h post infection, the

13、 medium is aspirated, the cells are lysed and HIV-1infection measured using the Luciferase Assay System. Luminescence is measured using a FLUOStar Optimamicroplate reader. Inhibition curves and the 50% (EC50) and 90% (EC90) effective concentrations are determined bynonlinear regression analysis, usi

14、ng GraphPad Prism software1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice3Administration 3 C57BL/6J (wild-type) and P2rx7-/- mice are used. The Nlrp3-/- mice are used. The NRTIs 3TC, AZT, and ABC or theP2X7 antagonist A438079 hydrochloride

15、 are dissolved in PBS. For CNV, each group of mice is injected once with 1 Lof NRTIs (3TC, 125 ng/L; ABC, 183 ng/L; AZT, 146 ng/L), 1 L of A438079 hydrochloride (3, 30, or 300 ng/L), orPage 2 of 3 www.MedChemEthe same volume of vehicle (PBS) into the vitreous humor using a 33-gauge needle immediatel

16、y after laser injury.Another group of mice is injected with 3TC (125 ng) in combination with an anti-mouse VEGF polyclonal antibody (10ng). Goat whole IgG (10 ng) is used as a biological control for the anti-mouse VEGF antibody.MCE has not independently confirmed the accuracy of these methods. They

17、are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Int J Antimicrob Agents. 2019 Dec;54(6):814-819. Heliyon. 2020 Jun. bioRxiv. 2020 May.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Gray LR, et al. The NRTIs lamivudine, stavudine and zidovudine have reduced HIV-1 inhibitory activ

18、ity in astrocytes. PLoS One. 2013 Apr 16;8(4):e62196.2. Hou P, et al. Genome editing of CXCR4 by CRISPR/cas9 confers cells resistant to HIV-1 infection. Sci Rep. 2015 Oct 20;5:15577.3. Mizutani T, et al. Nucleoside Reverse Transcriptase Inhibitors Suppress Laser-Induced Choroidal Neovascularization in Mice