Tenofovir Disoproxil (Bis(POC)-PMPA) is a nucleotide reverse transcriptase inhibitor to treat HIV and chronic Hepatitis B.

Tenofovir shows cytotoxic effects on cell viability in HK-2 cells, with IC₅₀ values of 9.21 and 2.77 μM at 48 and 72 h in MTT assay, respectively. Tenofovir diminishes ATP levels in HK-2 cells. Tenofovir (3.0 to 28.8 μM) increases oxidative stress and protein carbonylation in HK-2 cells. Furthermore, Tenofovir induces apoptosis in HK-2 cells, and that apoptosis is induced via mitochondrial damage^[1]. Tenofovir and M48U1 formulated in 0.25% HEC each inhibits the replication of both R5-tropic HIV-1_BaL and X4-tropic HIV-1_IIIb in activated PBMCs, and inhibits several laboratory strains and patient-derived HIV-1 isolates. The combined formulation of M48U1 and tenofovir in 0.25% HEC exhibits synergistic antiretroviral activity against infection with R5-tropic HIV-1_BaL, and is not toxic to PBMCs^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Tenofovir Disoproxil Fumarate (20, 50, 140, or 300 mg/kg) administered to BLT mice, shows dose dependent activity during vaginal HIV challenge in BLT humanized mice. Tenofovir Disoproxil Fumarate (50, 140, 300 mg/kg) significantly reduces HIV transmission in BLT mice^[3]. Tenofovir Disoproxil Fumarate (0.5, 1.5, or 5.0 mg/kg/day, p.o.) induces a dose-dependent decline in serum viremia in woodchucks chronically infected with WHV. Tenofovir Disoproxil Fumarate administration is safe and effective in the woodchuck model of chronic HBV infection^[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

519.44

C₁₉H₃₀N₅O₁₀P

201341-05-1

替诺福韦酯

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 38 mg/mL (73.16 mM)

* “≥” means soluble, but saturation unknown.

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, 6 months; -20°C, 1 month。-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。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.08 mg/mL (4.00 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.00 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.08 mg/mL (4.00 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.00 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.08 mg/mL (4.00 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.00 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Murphy RA, et al. Establishment of HK-2 Cells as a Relevant Model to Study Tenofovir-Induced Cytotoxicity. Int J Mol Sci. 2017 Mar 1;18(3)

  [2]. Musumeci G, et al. M48U1 and Tenofovir combination synergistically inhibits HIV infection in activated PBMCs and human cervicovaginal histocultures. Sci Rep. 2017 Feb 1;7:41018

  [3]. Wahl A, et al. Predicting HIV Pre-exposure Prophylaxis Efficacy for Women using a Preclinical Pharmacokinetic-Pharmacodynamic In Vivo Model. Sci Rep. 2017 Feb 1;7:41098

  [4]. Menne S, Cote PJ, Korba BE, Antiviral effect of oral administration of tenofovir disoproxil fumarate in woodchucks with chronic woodchuck hepatitis virus infection. Antimicrob Agents Chemother. 2005 Jul;49(7):2720-8.

Cells are plated into 48-well tissue culture plates (39,000 cells/mL) and allowed to grow for 48 h followed by treatment with vehicle or Tenofovir. Following the treatment period, cell viability is assessed using the MTT assay. The MTT assay relies on the conversion of tetrazolium dye 3-(4,5-dimethlthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to formazan by NAD(P)H-dependent oxidoreductases.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Twenty adult chronic WHV carrier woodchucks are stratified equally by age, sex, body weight, and serum GGT activity into five treatment groups consisting of four animals each: (i) Tenofovir Disoproxil Fumarate at 15.0 mg/kg once per day, (ii) Tenofovir Disoproxil Fumarate at 5.0 mg/kg/day, (iii) Tenofovir Disoproxil Fumarate at 1.5 mg/kg/day, (iv) Tenofovir Disoproxil Fumarate at 0.5 mg/kg/day, and (v) a placebo control. The woodchucks are treated daily for 4 weeks and observed for an additional 12 weeks following cessation of drug treatment.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Murphy RA, et al. Establishment of HK-2 Cells as a Relevant Model to Study Tenofovir-Induced Cytotoxicity. Int J Mol Sci. 2017 Mar 1;18(3)

  [2]. Musumeci G, et al. M48U1 and Tenofovir combination synergistically inhibits HIV infection in activated PBMCs and human cervicovaginal histocultures. Sci Rep. 2017 Feb 1;7:41018

  [3]. Wahl A, et al. Predicting HIV Pre-exposure Prophylaxis Efficacy for Women using a Preclinical Pharmacokinetic-Pharmacodynamic In Vivo Model. Sci Rep. 2017 Feb 1;7:41098

  [4]. Menne S, Cote PJ, Korba BE, Antiviral effect of oral administration of tenofovir disoproxil fumarate in woodchucks with chronic woodchuck hepatitis virus infection. Antimicrob Agents Chemother. 2005 Jul;49(7):2720-8.