Nevirapine is a non-nucleoside inhibitor of HIV-1 reverse transcriptase used to treat and prevent HIV/AIDS; with a K_i of 270 μM^[1].

Ki: 270 μM (HIV-1 reverse transcriptase)^[1]

Nevirapine itself is an inhibitor of only CYP3A4 at concentrations that are well above those of therapeutic relevance (K_i=270 μM)^[1]. Nevirapine has been used as a re-differentiation agent to treat cancers in several human cancer models. At all doses (100, 200, 350, 500 μM) tested, nevirapine significantly inhibits cell proliferation after 48 h treatment. At high dose (500 μM), nevirapine significantly increases the percentage of apoptotic cells compared with control^[2]. Nevirapine is a potent and selective inhibitor (IC₅₀=10-100 nM) of the replication of a wide variety of HIV-1 strains in several cellular assays^[3].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Nevirapine is available for use in combination with nucleoside HIV-1 reverse transcriptase inhibitors (e.g., zidovudine, didanosine, etc.). Nevirapine has received FDA approval for use in combination with HIV-1 protease inhibitors (e.g., saquinavir, ritonavir, indinavir, etc.). In humans, nevirapine is eliminated primarily in the urine as glucuronide conjugates of 2-, 3-, 8-, and 12-hydroxynevirapine^[1]. Nevirapine is completely absorbed in both sexes of mouse, rat, rabbit, monkey, and chimpanzee. Nevirapine is extensively metabolized in both sexes of all animal species studied^[4]. Nevirapine (9 mg/kg, 18 mg/kg and 36 mg/kg) shows significant reduction in ulcer severity score and ulcer index as compared to the control^[5]

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

266.30

C₁₅H₁₄N₄O

129618-40-2

奈韦拉平；萘维拉平；那韦拉平；奈韦那平；萘韦拉平

Room temperature in continental US; may vary elsewhere.

DMSO : 14.29 mg/mL (53.66 mM; Need ultrasonic)

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: ≥ 1.43 mg/mL (5.37 mM); Clear solution

  此方案可获得 ≥ 1.43 mg/mL (5.37 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 14.3 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% corn oil

  Solubility: ≥ 1.43 mg/mL (5.37 mM); Clear solution

  此方案可获得 ≥ 1.43 mg/mL (5.37 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 14.3 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Erickson DA, et al. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitornevirapine by human hepatic cytochromes P-450. Drug Metab Dispos. 1999 Dec;27(12):1488-95.

  [2]. Dong JJ, et al. In vitro evaluation of the therapeutic potential of nevirapine in treatment of human thyroid anaplastic carcinoma. Mol Cell Endocrinol. 2013 May 6;370(1-2):113-8.

  [3]. Merluzzi VJ, et al. Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. Science. 1990 Dec 7;250(4986):1411-3.

  [4]. Riska PS, et al. Biotransformation of nevirapine, a non-nucleoside HIV-1 reverse transcriptase inhibitor, in mice, rats, rabbits, dogs, monkeys, and chimpanzees. Drug Metab Dispos. 1999 Dec;27(12):1434-47.

  [5]. Onasanwo SA, et al. Evaluation of anti-ulcerogenic and ulcer-healing activities of nevirapine in rats. Afr J Med Med Sci. 2015 Sep;44(3):251-9.

FRO cells are seeded into 96-well culture plates at 10,000 cells/well. Cells are treated with different doses of nevirapine (0, 100, 200, 350 and 500 μM) for 48 h. MTT dye (5 mg/mL) is added to each well for additional 4 h, and the reaction is then stopped by the addition of DMSO. Optical density is measured at 490 nm on a multi-well plate reader^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Rats: Nevirapine and [¹⁴C] Nevirapine are dissolved together in absolute ethanol and methylene chloride (1:1, v/v) with mild heating. The concentration of drug in suspension is 2 mg/mL (20 mg/kg, 26 μCi) for oral dosing to rats and 6.7 mg/mL (20.3 mg/kg, 10 μCi males, 8.9 μCi females) for intraduodenal administration to rats before bile collection. The i.v. dose is administered to rats (1.1 mg/kg, 20 μCi) as a solution in 20% ethanol/80% saline^[4].

Mice: Nevirapine and [¹⁴C] Nevirapine are dissolved together in absolute ethanol and methylene chloride (1:1, v/v) with mild heating. The concentration of drug in suspension is 2 mg/mL (20 mg/kg, 2.5 μCi) with a specific activity of 5.55 μCi/mg for oral dosing to mice^[4].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Erickson DA, et al. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitornevirapine by human hepatic cytochromes P-450. Drug Metab Dispos. 1999 Dec;27(12):1488-95.

  [2]. Dong JJ, et al. In vitro evaluation of the therapeutic potential of nevirapine in treatment of human thyroid anaplastic carcinoma. Mol Cell Endocrinol. 2013 May 6;370(1-2):113-8.

  [3]. Merluzzi VJ, et al. Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. Science. 1990 Dec 7;250(4986):1411-3.

  [4]. Riska PS, et al. Biotransformation of nevirapine, a non-nucleoside HIV-1 reverse transcriptase inhibitor, in mice, rats, rabbits, dogs, monkeys, and chimpanzees. Drug Metab Dispos. 1999 Dec;27(12):1434-47.

  [5]. Onasanwo SA, et al. Evaluation of anti-ulcerogenic and ulcer-healing activities of nevirapine in rats. Afr J Med Med Sci. 2015 Sep;44(3):251-9.

Nevirapine is a non-nucleoside inhibitor of HIV-1 reverse transcriptase used to treat and prevent HIV/AIDS; with a K_i of 270 μM^[1].

Ki: 270 μM (HIV-1 reverse transcriptase)^[1]

Nevirapine itself is an inhibitor of only CYP3A4 at concentrations that are well above those of therapeutic relevance (K_i=270 μM)^[1]. Nevirapine has been used as a re-differentiation agent to treat cancers in several human cancer models. At all doses (100, 200, 350, 500 μM) tested, nevirapine significantly inhibits cell proliferation after 48 h treatment. At high dose (500 μM), nevirapine significantly increases the percentage of apoptotic cells compared with control^[2]. Nevirapine is a potent and selective inhibitor (IC₅₀=10-100 nM) of the replication of a wide variety of HIV-1 strains in several cellular assays^[3].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Nevirapine is available for use in combination with nucleoside HIV-1 reverse transcriptase inhibitors (e.g., zidovudine, didanosine, etc.). Nevirapine has received FDA approval for use in combination with HIV-1 protease inhibitors (e.g., saquinavir, ritonavir, indinavir, etc.). In humans, nevirapine is eliminated primarily in the urine as glucuronide conjugates of 2-, 3-, 8-, and 12-hydroxynevirapine^[1]. Nevirapine is completely absorbed in both sexes of mouse, rat, rabbit, monkey, and chimpanzee. Nevirapine is extensively metabolized in both sexes of all animal species studied^[4]. Nevirapine (9 mg/kg, 18 mg/kg and 36 mg/kg) shows significant reduction in ulcer severity score and ulcer index as compared to the control^[5]

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

266.30

C₁₅H₁₄N₄O

129618-40-2

奈韦拉平；萘维拉平；那韦拉平；奈韦那平；萘韦拉平

Room temperature in continental US; may vary elsewhere.

DMSO : 14.29 mg/mL (53.66 mM; Need ultrasonic)

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: ≥ 1.43 mg/mL (5.37 mM); Clear solution

  此方案可获得 ≥ 1.43 mg/mL (5.37 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 14.3 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% corn oil

  Solubility: ≥ 1.43 mg/mL (5.37 mM); Clear solution

  此方案可获得 ≥ 1.43 mg/mL (5.37 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 14.3 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Erickson DA, et al. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitornevirapine by human hepatic cytochromes P-450. Drug Metab Dispos. 1999 Dec;27(12):1488-95.

  [2]. Dong JJ, et al. In vitro evaluation of the therapeutic potential of nevirapine in treatment of human thyroid anaplastic carcinoma. Mol Cell Endocrinol. 2013 May 6;370(1-2):113-8.

  [3]. Merluzzi VJ, et al. Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. Science. 1990 Dec 7;250(4986):1411-3.

  [4]. Riska PS, et al. Biotransformation of nevirapine, a non-nucleoside HIV-1 reverse transcriptase inhibitor, in mice, rats, rabbits, dogs, monkeys, and chimpanzees. Drug Metab Dispos. 1999 Dec;27(12):1434-47.

  [5]. Onasanwo SA, et al. Evaluation of anti-ulcerogenic and ulcer-healing activities of nevirapine in rats. Afr J Med Med Sci. 2015 Sep;44(3):251-9.

FRO cells are seeded into 96-well culture plates at 10,000 cells/well. Cells are treated with different doses of nevirapine (0, 100, 200, 350 and 500 μM) for 48 h. MTT dye (5 mg/mL) is added to each well for additional 4 h, and the reaction is then stopped by the addition of DMSO. Optical density is measured at 490 nm on a multi-well plate reader^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Rats: Nevirapine and [¹⁴C] Nevirapine are dissolved together in absolute ethanol and methylene chloride (1:1, v/v) with mild heating. The concentration of drug in suspension is 2 mg/mL (20 mg/kg, 26 μCi) for oral dosing to rats and 6.7 mg/mL (20.3 mg/kg, 10 μCi males, 8.9 μCi females) for intraduodenal administration to rats before bile collection. The i.v. dose is administered to rats (1.1 mg/kg, 20 μCi) as a solution in 20% ethanol/80% saline^[4].

Mice: Nevirapine and [¹⁴C] Nevirapine are dissolved together in absolute ethanol and methylene chloride (1:1, v/v) with mild heating. The concentration of drug in suspension is 2 mg/mL (20 mg/kg, 2.5 μCi) with a specific activity of 5.55 μCi/mg for oral dosing to mice^[4].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Erickson DA, et al. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitornevirapine by human hepatic cytochromes P-450. Drug Metab Dispos. 1999 Dec;27(12):1488-95.

  [2]. Dong JJ, et al. In vitro evaluation of the therapeutic potential of nevirapine in treatment of human thyroid anaplastic carcinoma. Mol Cell Endocrinol. 2013 May 6;370(1-2):113-8.

  [3]. Merluzzi VJ, et al. Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. Science. 1990 Dec 7;250(4986):1411-3.

  [4]. Riska PS, et al. Biotransformation of nevirapine, a non-nucleoside HIV-1 reverse transcriptase inhibitor, in mice, rats, rabbits, dogs, monkeys, and chimpanzees. Drug Metab Dispos. 1999 Dec;27(12):1434-47.

  [5]. Onasanwo SA, et al. Evaluation of anti-ulcerogenic and ulcer-healing activities of nevirapine in rats. Afr J Med Med Sci. 2015 Sep;44(3):251-9.