nevirapine

Names

[ Name ]:
nevirapine

[Synonym ]:
11-Cyclopropyl-4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one
nevirapine
11-Cyclopropyl-4-methyl-5H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6(11H)-one
MFCD00866928
Viramune
6H-Dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one, 11-cyclopropyl-5,11-dihydro-4-methyl-
11-cyclopropyl-4-methyl-5H-dipyrido[2,3-e:2',3'-f][1,4]diazepin-6-one
11-Cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one

Biological Activity

[Description]:

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

[Related Catalog]:

Signaling Pathways >> Anti-infection >> HIV

Signaling Pathways >> Anti-infection >> Reverse Transcriptase

Research Areas >> Infection

[Target]

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

[In Vitro]

Nevirapine itself is an inhibitor of only CYP3A4 at concentrations that are well above those of therapeutic relevance (Ki=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].

[In Vivo]

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]

[Cell Assay]

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].

[Animal admin]

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].

[References]

[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.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
415.4±45.0 °C at 760 mmHg

[ Melting Point ]:
247°C

[ Molecular Formula ]:
C₁₅H₁₄N₄O

[ Molecular Weight ]:
266.298

[ Flash Point ]:
205.0±28.7 °C

[ Exact Mass ]:
266.116760

[ PSA ]:
63.57000

[ LogP ]:
2.03

[ Vapour Pressure ]:
0.0±1.0 mmHg at 25°C

[ Index of Refraction ]:
1.672

[ Storage condition ]:
-20°C Freezer

MSDS

Click to get detail MSDS

Safety Information

[ Hazard Codes ]:
Xi: Irritant;

[ Risk Phrases ]:
R36/37/38

[ Safety Phrases ]:
S26-S36-S36/37

[ RIDADR ]:
UN 2206 6.1/PG 3

[ WGK Germany ]:
3

[ Packaging Group ]:
III

[ Hazard Class ]:
6.1

[ HS Code ]:
2934994000

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2934994000

[ Summary ]:
2934994000. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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HAART associated hepatoxicity is an important cause of poor adherence to therapy in HIV infected persons. An initial manifestation is elevation in the level ofAlanine Transaminase (ALT) in blood. We s...

Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy: programmatic implications for countries phasing out stavudine.

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The World Health Organization Antiretroviral Treatment Guidelines recommend phasing-out stavudine because of its risk of long-term toxicity. There are two mutational pathways of stavudine resistance w...

HIV testing in pregnancy.

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