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Pharmaceutical composition for inhibiting immune response through inducing differentiation into regulator t cells and promoting proliferation of regulator t cells

A technology for suppressing immune response and composition, which is applied in the direction of drug combination, cell culture active agent, active ingredient of heterocyclic compound, etc., and can solve problems such as the effectiveness of suppressing immune response that has not been mentioned

Active Publication Date: 2015-11-18
LG CHEM LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the above-mentioned patent documents only disclose that the above-mentioned indole or indazole compounds inhibit cell necrosis and the activity associated with some necrosis-related diseases (such as liver diseases, neurodegenerative diseases, etc.), and never mention the above-mentioned compounds and regulatory T cells. relationship, efficacy in suppressing immune responses, or potential for use in the treatment of diseases associated with immune anaphylaxis

Method used

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  • Pharmaceutical composition for inhibiting immune response through inducing differentiation into regulator t cells and promoting proliferation of regulator t cells
  • Pharmaceutical composition for inhibiting immune response through inducing differentiation into regulator t cells and promoting proliferation of regulator t cells
  • Pharmaceutical composition for inhibiting immune response through inducing differentiation into regulator t cells and promoting proliferation of regulator t cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Example 1: Establishment of Allogeneic Immune Response Mouse Model

[0066] 6-8 week-old C57BL / 6 (H-2kb) mice and BALB / c (H-2kd) mice having different MHC classes from each other were purchased from OrientBioCo., Ltd. . The mice were used under their care after passing the regulations of the Administrative Committee of the Experimental Animal Department of The Catholic University of Korea. Recipient mice BALB / c (H-2kd) were irradiated with 800 cGy of whole body radiation. Within 24 hours, 5 × 10 cells isolated from donor mice C57BL / 6 (H-2kd) 6 bone marrow cells and 5 x 10 6 Spleen cells were transplanted intravenously into allogeneic recipient mice to induce a graft-versus-host rejection model. The bone marrow-transplanted mice were observed and evaluated for body weight, posture, activity, hair condition, and skin density (on a total 10-point scale with 2-point evaluation criteria for each item) (Table 1).

[0067] [Table 1]

[0068] score

Embodiment 2

[0069] Embodiment 2: flow cytometry (FACS analysis)

[0070] Mice were divided into groups in which (tetrahydropyran-4-yl)-[2-phenyl-5-(1,1-dioxo-thiomorpholin-4-yl)methyl-1H-indole- 7-yl]amine (LGLifeSciences Ltd., Daejeon, Korea, hereinafter referred to as "Compound A") treated GVHD group was used as a test group, and the GVHD group not treated with Compound A was used as a control group. Spleens from each group were isolated, followed by single cell isolation. The expression of CD4+CD25+Foxp3+, which is the phenotype of regulatory T cells, and CD4+IFN-γ cells and CD4+IL-4 cells were analyzed by using fluorescent monoclonal antibodies and flow cytometry.

Embodiment 3

[0071] Embodiment 3: the measurement of reactive oxygen species (ROS)

[0072] Animals in each group were sacrificed and their spleens were isolated. After isolation of single cells, the obtained cells were washed twice with phosphate-buffered saline (PBS). The reaction with 3 μM carboxy-H2DCFDA reagent was carried out at 37° C. for 10 minutes. After washing with PBS, analysis was performed with a flow cytometer at 540 nm.

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Abstract

The present invention relates to new medical use of (tetrahydropyran-4-yl)-[2-phenyl-5-(1,1-dioxo-thiomorpholine-4-yl)methyl-1H-indol-7-yl]amine, and more particularly, to a pharmaceutical composition containing the compound as an active ingredient, which is used for inhibiting an immune response, and / or for inducing differentiation into regulator T cells from undifferentiated T cells and / or promoting proliferation of regulator T cells.

Description

technical field [0001] The present invention relates to (tetrahydropyran-4-yl)-[2-phenyl-5-(1,1-dioxo-thiomorpholin-4-yl)methyl-1H-indol-7-yl ] New pharmaceutical uses of amines. More specifically, the present invention relates to the use of tetrahydropyran-4-yl)-[2-phenyl-5-(1,1-dioxo-thiomorpholin-4-yl)methyl-1H-indole The effects of -7-yl]amine on inducing differentiation and promoting the proliferation of regulatory T cells, as well as the immunomodulatory effect on activated regulatory T cells to prevent or treat various immune diseases (including graft-versus-host disease (GVHD)) a method for use in such a method; a pharmaceutical composition for use in such a method; and a method for obtaining regulatory T cells for preventing or treating an immune disease by using the pharmaceutical composition. Background technique [0002] Immunity refers to self-protection against foreign substances by recognizing and removing foreign antigenic substances present in the body. T...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/404A61K39/395A61K31/40A61P29/00
CPCA61K39/3955A61K45/06A61K31/203A61K31/54C07K16/2809C07K16/2818A61K2035/122C12N2501/15C12N2501/385C12N2501/51C12N2501/515C12N2501/999A61K31/541A61K38/1841C12N5/0637A61P29/00A61P37/00A61P37/06A61P37/08A61P43/00A61K39/46434A61K39/4621A61K39/46433A61K39/4611A61K2300/00A61K31/404C07D209/04A61K35/17
Inventor 赵锡九金娜延金恩贞林健一林廷延田恩珠
Owner LG CHEM LTD
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