阅读说明：本技术 阿法替尼在抗结核分枝杆菌药物中的应用 (Application of afatinib in anti-mycobacterium tuberculosis drugs ) 是由 杨倩婷 张明霞 邓国防 于 2019-09-18 设计创作，主要内容包括：本发明涉及阿法替尼在抗结核分枝杆菌药物中的应用。在临床上阿法替尼主要用于治疗恶性淋巴瘤、急性淋巴细胞白血病；而本发明研究发现其具有抗结核的作用,具有很好的开发价值；本发明涉及的阿法替尼在抗结核分枝杆菌药物中的应用以及阿法替尼具有明显的抗结核分枝杆菌的作用属于首次公开。(The invention relates to application of afatinib in an anti-mycobacterium tuberculosis drug. In clinic, afatinib is mainly used for treating malignant lymphoma and acute lymphocytic leukemia; the research of the invention finds that the compound has the anti-tuberculosis effect and has good development value; the application of afatinib in the anti-mycobacterium tuberculosis medicine and the obvious anti-mycobacterium tuberculosis effect of afatinib are disclosed for the first time.)

1. Application of afatinib in anti-mycobacterium tuberculosis drugs.

2. The use of claim 1, wherein said anti-mycobacterium tuberculosis drug is an in vivo anti-mycobacterium tuberculosis drug.

3. The use according to claim 1, wherein the Mycobacterium tuberculosis is Mycobacterium tuberculosis H₃₇Rv。

4. Application of afatinib in preparing antituberculosis drugs.

5. An anti-tuberculosis drug is characterized in that the active ingredient of the drug is afatinib.

6. The use of an anti-tuberculosis drug according to claim 6.

7. The use of an anti-tubercular drug according to claim 7, for the treatment of tuberculosis.

Technical Field

The invention relates to the technical field of bioengineering, and particularly relates to application of afatinib in an anti-mycobacterium tuberculosis drug.

Background

In the treatment of tuberculosis, the main challenges are: 1) the cure success rate of the multi-drug resistant tuberculosis (MDR-TB) is extremely low; 2) the treatment time of the existing antituberculosis standard short-term treatment scheme is still too long; and the relapse rate of the primary treatment of the sensitive tuberculosis is as high as 3% -9%. For the reasons mentioned above, this ancient infectious disease is again faced with the serious challenge of no drug being available. The first-line antituberculosis drugs used at present are developed more than 40 years ago, the novel effective antituberculosis drugs are slowly developed, and the drugs directly act on tubercle bacillus, so that the risk of cross drug resistance always exists.

Afatinib is a 4-anilinoquinazoline tyrosine kinase inhibitor in the form of a dibenzoate salt, Afatinib tablets are first-line (initial) therapeutic drugs for patients with metastatic non-small cell lung cancer (NSCLC), with common Epidermal Growth Factor Receptor (EGFR) mutations, Afatinib is a potent and selective, irreversible ErbB family blocker; afatinib covalently binds and irreversibly blocks signaling by all homodimers and heterodimers formed by the ErbB family members EGFR (ErbB1), HER2(ErbB2), ErbB3 and ErbB4, afatinib covalently binds to the kinase domains of EGFR (ErbB1), HER2(ErbB2) and HER4(ErbB4) and irreversibly inhibits tyrosine kinase autophosphorylation, resulting in down-regulation of ErbB signaling. Certain mutations in EGFR, including non-resistant mutations in its kinase domain, result in increased autophosphorylation of the receptor, resulting in receptor activation, which can also support cell proliferation in NSCLC in the absence of ligand binding. Non-resistant mutations are defined as occurring in exons making up the EGFR kinase domain, which result in increased receptor activation, and where efficacy is predicted by clinically meaningful tumor shrinkage and recommended doses of afatinib and/or inhibition of cell proliferation; the most common of these mutations are the exon 21L 858R substitution and the exon 19 deletion.

The molecular formula of afatinib is C₂₄H₂₅ClFN₅O₃Molecular weight of 485.94, and the structural formula is as follows:

the research finds that the medicine has the effect of resisting tuberculosis and has good development value.

Disclosure of Invention

The invention aims to research and develop a novel efficient antitubercular medicament, finds the antitubercular effect of afatinib and the application of afatinib in antitubercular mycobacteria medicaments, has high safety and good development value.

The technical scheme of the invention mainly relates to the application of afatinib in the anti-mycobacterium tuberculosis drugs.

Further, the Mycobacterium tuberculosis is specifically Mycobacterium tuberculosis H₃₇Rv。

The invention also provides application of afatinib in preparation of anti-tuberculosis drugs.

In one embodiment of the present invention, an anti-tuberculosis drug with afatinib as an active ingredient is provided. The antituberculosis drug can be used for treating tuberculosis.

The invention has the advantages that:

(1) the invention discovers for the first time that afatinib has an obvious anti-mycobacterium tuberculosis effect, and as a potential HDT-targeting drug, afatinib is approved by FDA, has high safety and has good development value;

(2) the invention provides the application of afatinib in the preparation of anti-tuberculosis drugs for the first time;

(3) the invention discovers that afatinib can remarkably enhance the cell killing of tubercle bacillus in cells.

Drawings

FIG. 1 is a graph of the effect of various concentrations of afatinib on cell viability in example 1 of the present invention;

FIG. 2 is a graph showing the effect of afatinib on the survival of Mycobacterium tuberculosis in cells in example 2 of the present invention.

Detailed Description

The invention is further described with reference to the following figures and detailed description, which are intended to illustrate, but not to limit the invention further.

The technical means used in the following examples are conventional means well known to those skilled in the art, and all raw materials are general-purpose materials.