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Application of histone deacetylase HDAC11 inhibitor in preparation of medicine for preventing and treating fungal infection

A deacetylase, fungal infection technology, applied in the direction of antifungal agents, pharmaceutical formulations, medical preparations containing active ingredients, etc. horizontal effect

Active Publication Date: 2022-02-11
SHENZHEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In view of the above-mentioned deficiencies in the prior art, the object of the present invention is to provide a histone deacetylase HDAC11 inhibitor in the preparation of the application of drugs for the prevention and treatment of fungal infections, aiming to solve the problem that no suitable regulation-based Issues with host autoimmunity exerted to enable drugs against fungal infections

Method used

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  • Application of histone deacetylase HDAC11 inhibitor in preparation of medicine for preventing and treating fungal infection
  • Application of histone deacetylase HDAC11 inhibitor in preparation of medicine for preventing and treating fungal infection
  • Application of histone deacetylase HDAC11 inhibitor in preparation of medicine for preventing and treating fungal infection

Examples

Experimental program
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Effect test

Embodiment 1

[0055] In order to analyze and verify the role of HDAC11 in antifungal immunity, this example established HDAC11 wild-type and HDAC11-deficient mouse models of systemic infection with Candida albicans, and further studied the role of HDAC11 in antifungal immunity.

[0056] Materials and reagents mainly involved in this embodiment and their sources:

[0057] Hdac11 knockout mice were purchased from Cyagen (Suzhou). The mice were knocked out of exons 3 to 6 of the Hdac11 allele by CRISPR-Cas9 technology. HDAC11 wild-type (Hdac11 + / + ) and HDAC11-deficient (Hdac11 - / - ) mice through heterozygous Hdac11 + / - Obtained by cross breeding of mice; Ly-6G antibody (65140-1-Ig) was purchased from Proteintech Company.

[0058] Ten 8-9-week-old HDAC11 wild-type (Hdac11 + / + ) and HDAC11-deficient (Hdac11 - / - ) male mice, counted as "0" day after the initial weighing, each mouse was injected with 2×10 5 CFU of Candida albicans (Candida albican, SC5314 strain) in PBS to establish a system...

Embodiment 2

[0067] Further, in order to analyze the role of HDAC11 in antifungal immunity, Hdac11 was studied in this example + / + and Hdac11 - / - Expression of NOS2 / iNOS in nephros of mice systemically infected with Candida albicans.

[0068] The main reagents involved in this embodiment and their sources:

[0069] Trizol, M-MLV reverse transcriptase, and dNTP were purchased from Takara; Oligo dT 18 and detection primers were synthesized by Shanghai Sangon; SYBR Green master mix was purchased from Shanghai Yisheng Biotechnology Co., Ltd.; cell lysate was purchased from CST Company; protease inhibitor cocktail was purchased from Roche Company; BCA protein quantification reagent was purchased from Thermo Fisher ; iNOS antibody (AF7281) was purchased from Shanghai Biyuntian Biotechnology Co., Ltd.; β-actin antibody (66009-1-Ig) was purchased from Proteintech Company.

[0070] In this embodiment, the sequences of the mouse gene detection primers involved are as follows:

[0071] Mouse NOS2...

Embodiment 3

[0087] Further, in order to analyze the role of HDAC11 in antifungal immunity, this example induced Hdac11 by different fungal ligands + / + and Hdac11 - / - Mouse bone marrow-derived macrophage BMDM expressed NOS2 / iNOS for research and testing.

[0088] The main reagents involved in this embodiment and their sources:

[0089] Mouse macrophage colony-stimulating factor was purchased from R&D Company; HKCA (tlrl-hkca), Zymosan (tlrl-zyn), TDB (tlrl-tdb) were purchased from Invivogen Company; α-mannan (M3640) was purchased from Sigma Company.

[0090] 1) Induction and culture of mouse bone marrow-derived macrophage BMDM

[0091] respectively from Hdac11 + / + and Hdac11 - / - Bone marrow cells were isolated from mouse femurs and tibias, and red blood cells were depleted using a hypotonic solution. The cells were induced and cultured in RIPM-1640 conditioned medium containing 10% fetal bovine serum, 1% penicillin-streptomycin (100 μg / mL), and 20 μg / mL mouse macrophage colony-stimula...

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Abstract

The invention discloses application of a histone deacetylase HDAC11 inhibitor in preparation of a medicine for preventing and treating fungal infection. The histone deacetylase HDAC11 inhibitor can promote the transcription enhancement of NOS2 gene, promote the expression increase of NOS2 gene coding protein iNOS and improve the production level of nitric oxide (NO) and reactive oxygen species (ROS) by regulating and controlling a Syk signal channel, so that the fungus killing capacity of cells is enhanced, and the histone deacetylase HDAC11 inhibitor plays a key role in inhibiting proliferation of invasive fungi in tissues and organs and protecting the tissues from being damaged by the fungi. According to the invention, the histone deacetylase HDAC11 inhibitor can activate the self-antibacterial immune function of a host, and can be used for preparing a medicine based on an antifungal immune regulation therapy.

Description

technical field [0001] The invention relates to the field of antifungal drugs, in particular to the application of a histone deacetylase HDAC11 inhibitor in the preparation of drugs for preventing and treating fungal infections. Background technique [0002] Fungal infection is a clinical common disease and frequently-occurring disease. According to the different parts of the human body, pathogenic fungi are clinically divided into superficial fungi and deep fungi. Superficial fungal infections generally only invade the skin, while deep fungi can invade human skin, mucous membranes, deep tissues and internal organs, and even cause systemic disseminated infections. [0003] At present, the antifungal drugs routinely used in clinical practice mainly include azoles, polyenes, allylamines, echinocandins, nucleoside analogs, etc. These antifungal drugs have a high probability of producing drug-resistant strains and have large side effects. The ability to improve the host's micr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/497A61P31/10
CPCA61K31/497A61P31/10Y02A50/30
Inventor 陈玮琳吴晗尹小凡
Owner SHENZHEN UNIV
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