Drug for resisting HIV latency and applications thereof

A drug and application technology, applied in the field of drugs for the treatment of AIDS, can solve the problems of high toxicity and side effects

Inactive Publication Date: 2014-10-01
FUDAN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this strategy has several treatment options in clinical practice, the results are still unsatisfactory. Either the activator is ineffective, or it is effective but has severe s...

Method used

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  • Drug for resisting HIV latency and applications thereof
  • Drug for resisting HIV latency and applications thereof
  • Drug for resisting HIV latency and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0086] Example 1 Effect of Oxaliplatin on HIV Latent Induction and Activation

[0087] C11 cell is a latently infected cell model of HIV, which is obtained by infecting human T lymphocyte cell line Jurkat with HIV-1 lentivirus carrying EGFP reporter gene, through cell sorting and HIV integration detection, and has HIV integration but no expression EGFP T lymphocyte line. C11 cells are Jurkat stable strains that are infected by HIV lentivirus carrying the reporter gene GFP while not expressing, so they are used to screen for drugs that activate latent HIV-1 infection (see the technology disclosed in application number CN200810038851.X), and the preservation number is CCTCC NO .C200821.

[0088] In this example, 2×10 per well 4 For each cell, C11 cells were seeded in a 96-well plate, and 100 μl of 1640 medium (Gibco) containing 10% FBS (Gibco) was added to each well. After 24 hours, oxaliplatin (Oxaliplatin(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O')platinum(II), purch...

Embodiment 2

[0089] Example 2 Effect of Dilazole on HIV Latent Induction and Activation

[0090] Repeat Example 1, the only difference is that dilazep3-(4-{3-[(3,4,5-trimethoxyphenyl)carbonyloxy]propyl}-1,4-diazepan-1-yl)propyl-3 , 4,5-trimethoxybenzoate, purchased from Tocris) 10μM to treat the cells.

[0091] The result is as Figure 1~3 as shown, figure 1 The photos of the bright field and dark field of the undoped (mock) group; figure 2 It is the photo of the bright field and dark field of the oxaliplatin treatment group; image 3 Process brightfield and darkfield photographs for Dilazo. Fluorescent photographs have been destained to make the fluorescent cells white for easy identification on printed text.

[0092] The results showed that the proportion of green fluorescent positive cells in HIV latently infected cells was as high as 16% after treatment with oxaliplatin and dilazole respectively; the proportion of fluorescent positive cells in HIV latent infected cells not treate...

Embodiment 3

[0093] Example 3 Effects of different concentrations of oxaliplatin and dilazole on HIV latency-induced activation

[0094] Example 1 was repeated except that the cells were treated with oxaliplatin at final concentrations of 2.5 μM, 5 μM, 10 μM, and 20 μM and diazepam at concentrations of 10 μM, 20 μM, 40 μM, and 60 μM.

[0095] The result is as Figure 4 as shown, Figure 4 Shows the effect of different concentrations of oxaliplatin and dilazole on HIV latency-induced activation. C11 cells were treated with different concentrations of oxaliplatin and dilazole for 48 hours, and the proportion of GFP+ cells was analyzed by flow cytometry. The above data are the average value of the data obtained from 3 independent experiments. Sodium valproate (valproic acid, VPA; Sigma T8552) was used as a positive control drug, and its concentration was 0.5 μM, 1 μM, 2 μM, 4 μM.

[0096] Oxaliplatin (μM)

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PUM

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Abstract

The invention relates to a drug for resisting HIV latency and applications thereof, and specifically relates to the HIV latency resisting effect of oxaliplatin and dilazep and the applications of oxaliplatin and dilazep in preparation of drugs for treating AIDS. Oxaliplatin and dilazep both has the HIV latency resisting effect, can be cooperatively used with antiretroviral drugs to eliminate activated cells that has been subjected to latent infection so as to accelerate the elimination of latent virus reservoir, and can be further used to prepared novel anti-AIDS drugs. The invention provides a novel way for radically curing AIDS.

Description

technical field [0001] The invention belongs to the field of medicine, and relates to medicines for treating AIDS, in particular to two kinds of medicines with anti-HIV latent effects and their uses, especially to the anti-HIV latent effects of oxaliplatin and dilazole and their use in the preparation of medicines for treating AIDS. application. Background technique [0002] Acquired Immunodeficiency Syndrome (AIDS) is a serious infectious disease caused by human immunodeficiency virus (HIV). According to WHO statistics, there are more than 40 million AIDS patients in the world, with 5 million new patients and 3 million deaths each year. At present, the clinical treatment of AIDS mainly adopts Highly active antiretroviral therapy (HAART), which not only effectively controls HIV replication, but also can rebuild the immune function of AIDS patients, opening the door of hope for the treatment of AIDS . People once hoped to completely eliminate HIV in the body by virtue of H...

Claims

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Application Information

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IPC IPC(8): A61K31/282A61K31/551A61P31/18
Inventor 朱焕章刘思杰张龙飞
Owner FUDAN UNIV
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