Amprenavir is a selective HIV protease inhibitor with a Ki value of 0.6nM. The IC50 value of amprenavir against wild-type clinical HIV isolates in vitro is 14.6 ± 12.5ng/mL.[3] Treatment of Huh-7 cells with amprenavir (50μM) significantly inhibited invasion, blocked the conversion of latent MMP-2 to its 62/64-kD active form, but had no effect on cell proliferation compared to the DMSO-treated controls. Treatment with amprenavir via intragastric gavage (60 mg/kg/d, 5 days/week) for 3 weeks delayed tumor growth in nude mice inoculated with hepatoma Huh-7 cells.[4]
作用机制
Amprenavir prevents the virally encoded HIV protease from processing the cleavage of its natural substrates, gag and gag-pol polyproteins. It exerts the antiretroviral effect late in the HIV life cycle by interfering with virion maturation.[3]
To evaluate the protective effect of Amprenavir against pepsin-induced cell dissociation. Results showed that 10 µM Amprenavir completely reversed pepsin-induced cell dissociation, while 1 µM Amprenavir partially reversed it.
Int J Mol Sci. 2023 Apr 5;24(7):6765.
Caco-2 cells
10 or 100 µM
1 hour
To assess the permeability of GW433908 and its metabolic conversion in Caco-2 cell monolayers. Results showed that GW433908 did not substantially cross the monolayer, whereas APV crossed ~250-fold faster than GW433908. Additionally, GW433908 generated a significant amount of APV in the compartment where it was applied.
To evaluate the protective effect of Amprenavir against pepsin-mediated upregulation of matrix metalloproteinases (MMPs). Results showed that 10 µM Amprenavir significantly reduced the expression of MMP1, MMP7, MMP9, and MMP14.
Int J Mol Sci. 2023 Apr 5;24(7):6765.
RAW 264.7 mouse macrophages
10 µM
18 hours
To test the effect of Amprenavir on cholesterol efflux, results showed no effect at 10 μmol/L concentration.
To evaluate the protective effect of Amprenavir against pepsin-mediated E-cadherin cleavage. Results showed that 10 µM Amprenavir significantly reversed E-cadherin cleavage, while 1 µM Amprenavir partially reversed it.
Int J Mol Sci. 2023 Apr 5;24(7):6765.
HIV-1 protease mutant L90M
0.16 nM
Determination of the inhibition constant of APV for mutant L90M
FEBS J. 2010 Sep;277(18):3699-714.
HIV-1 protease mutant I84V
0.9 nM
Determination of the inhibition constant of APV for mutant I84V
FEBS J. 2010 Sep;277(18):3699-714.
HIV-1 protease mutant I54V
0.41 nM
Determination of the inhibition constant of APV for mutant I54V
FEBS J. 2010 Sep;277(18):3699-714.
HIV-1 protease mutant I54M
0.50 nM
Determination of the inhibition constant of APV for mutant I54M
FEBS J. 2010 Sep;277(18):3699-714.
HIV-1 protease mutant I50V
4.5 nM
Determination of the inhibition constant of APV for mutant I50V
FEBS J. 2010 Sep;277(18):3699-714.
HIV-1 protease mutant V32I
1.5 nM
Determination of the inhibition constant of APV for mutant V32I
FEBS J. 2010 Sep;277(18):3699-714.
HIV-1 protease wild type
0.15 nM
Determination of the inhibition constant of APV for wild-type HIV-1 protease
FEBS J. 2010 Sep;277(18):3699-714.
Amprenavir/安瑞那韦 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Beagle dogs
Beagle dogs
Oral
35 mg/kg
Single dose
To evaluate the pharmacokinetic parameters of GW433908 calcium salt in beagle dogs. Results showed that GW433908 exposure in the portal vein was minimal (only 0.85% of APV exposure), indicating that GW433908 is primarily converted to APV in the gastrointestinal tract with minimal liver exposure.
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