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Retrovirus-infection inhibitor

a technology of retrovirus and infector, applied in the field of retrovirus infection inhibitor, can solve problems such as difficult clinical application, and achieve the effect of reducing cytotoxicity

Inactive Publication Date: 2010-03-04
NAGASAKI UNIVERSITY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0009]The retrovirus-infection inhibitor provided by the present invention inhibits intracellular entry of retrovirus, particularly human immunodeficiency virus (HIV), and shows reduced cytotoxicity as compared to conventional ones.

Problems solved by technology

However, since fenretinide shows high cytotoxicity, its clinical application is difficult.

Method used

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  • Retrovirus-infection inhibitor
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  • Retrovirus-infection inhibitor

Examples

Experimental program
Comparison scheme
Effect test

example 1

HIV infection suppressive action and cell Proliferation Suppressive Action-1

Method

(1) Reagent

[0050]Fenretinide (BIOMOL Research Laboratories Inc.), GGA (supplied by Dr. Shidouji of Siebold University of Nagasaki) and NIK-333 (Kowa Pharmaceutical Co., Ltd.) were each dissolved in ethanol to 5 mM, 5 mM and 50 mM to give stock solutions. The stock solutions were divided into small portions each for one time use and preserved at −20° C. until use.

(2) Cells

[0051]NP2 is a cell line derived from human glioma, TE671 is a cell line derived from human rhabdomyosarcoma, and HeLa is a cell line derived from human uterus cancer. Human NP2 cell and NP2 cell (NP2 / CD4 / X4 cell) that expresses CD4 and CXCR4, which are infection receptors of HIV, were supplied by Dr. Hoshino of Gunma University (Soda, Y., Shimizu, N., Jinno, A., Liu, H. Y., Kanbe, K., Kitamura, T., and Hoshino, H. 1999. Establishment of a new system for determination of coreceptor usages of HIV based on the human glioma NP-2 cell line...

example 2

Influence on HIV Infection Receptor Expression

Method

[0066]Fenretinide and GGA were added to Dulbecco-modified Eagle medium (Sigma Ltd. or Wako) containing 2% fetal bovine serum and antibiotic, to 2 μM and 20 μM, respectively. The target cells (HeLa / CD4 cell or NP2 / CD4 / X4 cell) were cultured in the medium for 2 days at 37° C. in the presence of 5% CO2. HeLa / CD4 cell and NP2 / CD4 / X4 cell were similar to those used in Example 1. The cells were treated with fenretinide or GGA and stained with anti-CD4 antibody conjugated with FITC (Sigma Ltd.). As a control, cells treated in the same manner except antibody was not used (Ab(−)) and cells treated in the same manner except the treatment with fenretinide or GGA was not performed (Ab(+)) were also examined. The fluorescence intensity of each cell was measured by a cytometer (Coulter) and evaluated as a cell surface expression amount of CD4. In the same manner, the cell treated with fenretinide or GGA was stained with rat anti-CXCR4 antibody (...

example 3

HIV-Infection Suppressive Action and Cell Proliferation Suppressive Action-2

Method

[0069]In the same manner as in Example 1, the HIV-infection suppressive action and cell proliferation suppressive action of GGA, fenretinide and NIK-333, which are retinoids, were examined. Examined were NP2 / CD4 / X4 cell, TE671 / CD4 cell and HeLa / CD4 cell. The HIV-infection suppressive action and cell proliferation suppressive action of GGA are shown in FIG. 11, the HIV-infection suppressive action and cell proliferation suppressive action of fenretinide are shown in FIG. 12, and the HIV-infection suppressive action and cell proliferation suppressive action of NIK-333 are shown in FIG. 13.

[0070]All retinoids suppressed CXCR4-tropic HXB2 HIV-1 vector infection in a concentration-dependent manner in NP2 / CD4 / X4 cell, TE671 / CD4 cell and HeLa / CD4 cell. These retinoids also suppressed cell proliferation. For example, when NP2 / CD4 / X4 cell was treated with GGA (20 μM), HIV-1 vector infection was suppressed to 10...

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Abstract

An infection inhibitor of retrovirus, particularly human immunodeficiency virus, comprising, as an active ingredient, at least one compound selected from the group consisting of a compound represented by the formula (I) (GGA) or a salt thereof, a compound represented by the formula (II) (NIK-333) or a salt thereof, and derivatives thereof.

Description

TECHNICAL FIELD[0001]The present invention relates to a retrovirus-infection inhibitor. More particularly, the present invention relates to an infection inhibitor of retrovirus such as human immunodeficiency virus and the like, comprising a certain retinoid analog as an active ingredient.BACKGROUND ART[0002]Retrovirus is a generic term of viruses belonging to Retroviridae, which have RNA as genome, and synthesize, in the primary step of self-replication, DNA using RNA as a template by the action of reverse transcriptase (RNA dependent DNA polymerase) they have. Retroviridae consists of three subfamilies (Oncovirinae, Lentivirinae, Spumavirinae). Retrovirus is known to infect and proliferate in various animals such as birds and mammals as hosts, and cause sarcoma, leukemia, cancer and the like. As retrovirus using human as a host, human T cell leukemia virus (HTLV), human immunodeficiency virus (HIV) and the like have been reported. HIV is known as a causative virus of acquired immun...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/191C07C57/03A61P31/18
CPCA61K31/202A61P31/12A61P31/14A61P31/18A61P43/00
Inventor KUBO, YOSHINAOKAMIYAMA, HARUKA
Owner NAGASAKI UNIVERSITY
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