阿昔洛韋作用機制 - Medchemexpress - MCE中國

1、Product Data SheetAcyclovirCat. No.: HY-17422CAS No.: 59277-89-3分式: CHNO分量: 225.2作靶點: HSV; Apoptosis; Bacterial作通路: Anti-infection; Apoptosis儲存式: Powder -20°C 3 years4°C 2 yearsIn solvent -80°C 6 months-20°C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 50 mg/mL (222.02 mM)* "" means soluble

2、, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 4.4405 mL 22.2025 mL 44.4050 mL5 mM 0.8881 mL 4.4405 mL 8.8810 mL10 mM 0.4440 mL 2.2202 mL 4.4405 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：-80°C, 6 months; -20°C, 1 month。-80°C 儲存時，請在 6

3、 個內(nèi)使，-20°C 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(dāng)?shù)娜芙獍?。以下溶解案都請先按?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(dāng)保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)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 (11.10 mM); Clear

4、 solution此案可獲得 2.5 mg/mL (11.10 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 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% corn oilSolubility: 2.5 mg/mL (11.10 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (11.10 mM，飽和度未知)

5、 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 Acyclovir (Aciclovir) 種鳥嘌呤類似物和種服活性的抗病毒劑。Acyclovir 具有抗 HSV-1 (IC50 為 0.85 M)，HSV-2 (IC50 為 0.85 M) 和痘帶狀皰疹病毒的活性。Acyclovir 可被病毒胸苷激酶 (TK) 磷酸化，三磷酸 Acyclovir 通過鳥苷三磷酸的競爭性抑制和強制性鏈終來擾病毒 DNA 聚合。Acyclovir

6、 可預(yù)防急性病的誘導(dǎo)療法中的細菌感染。IC & Target IC50: 0.85 M (HSV-1); 0.86 M (HSV-2)2體外研究 Acyclovir (3-100 µM; 24-72 hours; Jurkat, U937, and K562 leukemia cells) treatment shows a dose- and time-dependent reduction of cell viability3.Acyclovir (10-100 µM; 24-72 hours; Jurkat cells) treatment shows a d

7、elay/block in S phase and an increase of the sub-G1 peak3.Acyclovir (10-100 µM; 24-72 hours; Jurkat cells) treatment activates caspase-3 and presences nuclear DNAfragmentation, thereby indicating apoptotic cell death3.In HSV-infected cells, HSV thymidine kinase (HSV-TK) specifically phosphoryla

8、te Acyclovir to its monophosphate, andthis activation confers a high degree of selectivity of the drugs. Thereafter, the monophosphate is furtherphosphorylated to the diphosphate (Acyclovir -DP) and triphosphate (Acyclovir -TP) by cellular kinases. Thetriphosphate is the fully activated metabolite t

9、hat is toxic to the virus4.Cell Viability Assay3Cell Line: Jurkat, U937, and K562 leukemia cellsConcentration: 3 µM, 10 µM, 30 µM, 100 µMIncubation Time: 24 hours, 48 hours, and 72 hoursResult: Showed a dose- and time-dependent reduction of cell viability.Cell Cycle Analysis3Cell

10、 Line: Jurkat cellsConcentration: 10 µM, 100 µMIncubation Time: 24 hours, 48 hours, and 72 hoursResult: Revealed a dose-dependent accumulation of cells in S phase after 24 and 48 h.Showed a dose-dependent increase of the sub-G1 hypodiploid peak after 72 h.Apoptosis Analysis3Cell Line: Jurk

11、at cellsConcentration: 10 µM, 100 µMIncubation Time: 24 hours, 48 hours, and 72 hoursResult: Induced cell apoptosis.Page 2 of 3 www.MedChemE體內(nèi)研究 Acyclovir (20 mg/kg; oral administration; three times daily; for 10 days; BALB/c mice) treatment in infected micesuppresses the development of sk

12、in lesions and results in a dissociation between DTH response and antibody production1.Animal Model: Specific-pathogen-free BALB/c mice (7-week-old) infected with HSV-11Dosage: 20 mg/kgAdministration: Oral administration; three times daily; for 10 daysResult: Suppressed the development of skin lesio

13、ns and resulted in a dissociation betweenDTH response and antibody production.REFERENCES1. Li Z, et al. Acyclovir treatment of skin lesions results in immune deviation in mice infected cutaneously with herpes simplex virus. Antivir ChemChemother. 1999 Sep;10(5):251-7.2. Suzuki M, et al. Synergistic

14、antiviral activity of acyclovir and vidarabine against herpes simplex virus types 1 and 2 and varicella-zoster virus. Antiviral Res.2006 Nov;72(2):157-61.3. Benedetti S, et al. Acyclovir induces cell cycle perturbation and apoptosis in Jurkat leukemia cells, and enhances chemotherapeutic drug cytoto

15、xicity. LifeSci. 2018 Dec 15;215:80-85.4. Hayashi K, et al. The role of a HSV thymidine kinase stimulating substance, scopadulciol, in improving the efficacy of cancer gene therapy. J Gene Med.2006 Aug;8(8):1056-67.5. Lönnqvist B, et al. Oral acyclovir as prophylaxis for bacterial infections during induction therapy for acute leukaemia in adults. The Leukemia Group ofMiddle Sweden. Support Care Cancer. 1993 May;1(