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Novel use of Polymerase I inhibitor

A technology of inhibitor and immunosuppressant, applied in the field of biomedicine, can solve the problem that the effect of CX-5461 has not been reported, and achieve the effect of inhibiting the proliferation of T cells and having great application prospects.

Active Publication Date: 2018-11-30
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, there is no report on the role of CX-5461 in immunosuppression

Method used

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  • Novel use of Polymerase I inhibitor
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  • Novel use of Polymerase I inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1Cx5461

[0047] Example 1 Cx5461 affects T cell activation by inhibiting the proliferation of T cells

[0048] Dissolve Cx5461 in dimethyl sulfoxide (DMSO) to prepare Cx5461 solution for the following experiments:

[0049] 1. Inoculate Jurkat T cells in a six-well plate in RPMI1640 medium containing 10% fetal bovine serum, and divide them into four groups.

[0050] (1) Stimulation group (P / I): Add PMA / Ionmycin solution to each well;

[0051] (2) Positive control group (P / I+FK506): Add FK506 solution to each well until the concentration of FK506 is 1×10 -6 M;

[0052] (3) Experimental group (P / I+Cx5461): Add Cx5461 solution to each well until the concentration of Cx5461 is 1×10 -6 M;

[0053] (4) Control group (Con): add an equal volume of DMSO to each well;

[0054] Immunofluorescence experiments were performed after the above four groups were cultured at 37° C. for 6 hours. Suspend Jurkat T cells in 50 mL medium, install filter paper and fix slides on the cell spinner, then add ...

Embodiment 2Cx546

[0077] Example 2 Cx5461 Delays the Rejection of Skin Allografts at the Animal Experimental Level

[0078] Take 2 g of Cx5461 and dissolve it in 1 mL of DMSO. After the dissolution is complete, add physiological saline to supplement the volume, so that the final concentration of Cx5461 is 0.5 g / L, 1.0 g / L, and 2.0 g / L to obtain a Cx5451 solution. experiment:

[0079] 1. Mouse skin transplantation experiment

[0080] (1) Establishment of mouse skin graft model

[0081] C57BL / 6 and C57BL / 6 at the age of 6-8 weeks were purchased from the Guangdong Provincial Medical Experimental Animal Center and kept in the feeding room of Shenzhen Graduate School of Tsinghua University. Two days before the operation, the recipient C57BL / 6 mice were depilated; BALB / c mice and C57BL / 6 mice were anesthetized with 10% sodium pentobarbital, and then treated with 75% ethanol for donor and C57BL / 6 mice. The skin on the back of the recipient mouse is sterilized. The back skin of the donor mice was r...

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Abstract

The invention belongs to the technical field of biological medicine and specifically discloses a novel use of a Polymerase I inhibitor. The novel use of the Polymerase I inhibitor is studied in the cellular level and the animal experimental level. The Polymerase I inhibitor can inhibit the activity of IL-2, NFATc2, NFkB and IFN-gamma thereby inhibiting the proliferation of T cells, further regulating and controlling the T cell activation and the immune response of the human body and inhibiting the immune rejection of the organ allograft. The Polymerase I inhibitor can be used for preparation of agents for inhibiting the activity of IL-2, NFATc2, NFkB and IFN-gamma, T cell proliferation, T cell activation or immune rejection of the organ allograft and has a large application prospect.

Description

technical field [0001] The invention belongs to the technical field of biomedicine. More specifically, it relates to the use of Polymerase I inhibitors in the preparation of immunosuppressants. Background technique [0002] The existence of the immune system is to prevent the invasion of pathogenic bacteria, but some cells, tissue proteins or other components in some individuals will have an abnormal immune reaction with the immune system, and the individual will produce T cells that attack their own cells or any proteins outside the cells or Lesions caused by autoantibodies are autoimmune diseases. The etiology of autoimmune diseases is extremely complex, so the current clinical treatment can only start from the symptoms of the appearance, such as giving patients immunosuppressants to relieve their pain. In a broad sense, drugs that can reduce immunity are called immunosuppressants, which can reduce immunity after taking or injection. Therefore, immunosuppressants are ma...

Claims

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Application Information

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IPC IPC(8): A61K31/551A61P37/06
CPCA61K31/551A61P37/06
Inventor 陈红波蔡湘仪杨敏吴彦萍邓文斌
Owner SUN YAT SEN UNIV
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