阅读说明：本技术 Huwe1抑制剂bi8626在制备抑制炎症小体激活的药物中的应用 (Application of HUWE1 inhibitor BI8626 in preparation of medicines for inhibiting activation of inflammasome ) 是由 齐晓朋 徐涛 郭宇 李艺辉 于 2020-05-18 设计创作，主要内容包括：本发明提供了HUWE1抑制剂BI8626在制备抑制炎症小体激活的药物中的应用,属于生物医药技术领域。BI8626在小鼠BMDM细胞中可显著抑制NLRP3,AIM2和NLRC4炎症小体的激活,显著降低半胱氨酸蛋白酶-1(Caspase-1)的活化,降低细胞的死亡。本发明首次证实HUWE1抑制剂BI8626在制备抑制炎症小体激活的药物中的新用途,可用于抑制炎症小体的激活,降低细胞的死亡,表明BI8626在治疗炎症小体异常激活疾病(如痛风,II型糖尿病,系统性红斑狼疮等炎症性疾病)中具有潜在药用价值。(The invention provides an application of HUWE1 inhibitor BI8626 in preparation of a medicine for inhibiting activation of inflammatory corpuscles, and belongs to the technical field of biological medicines.BI 8626 can obviously inhibit activation of N L RP3, AIM2 and N L RC4 inflammatory corpuscles in mouse BMDM cells, obviously reduce activation of cysteine proteinase-1 (Caspase-1), and reduce death of cells.)

Use of HUWE1 inhibitor BI8626 for the manufacture of a medicament for inhibiting the activation of inflammasome; the chemical structural formula of the BI8626 is shown as a formula I;

2. the use of claim 1, wherein the inflammasome comprises N L RP3, AIM2 or N L RC 4.

3. The use of claim 2, wherein the N L RP3 is activated by lipopolysaccharide and adenosine triphosphate together, the AIM2 is activated by dsDNA, and the N L RC4 is activated by Salmonella.

4. A medicament for inhibiting activation of inflammasome, comprising an active ingredient BI8626 and a pharmaceutically acceptable carrier.

Use of HUWE1 inhibitor BI8626 for the manufacture of a medicament for the treatment of inflammatory diseases.

6. The use according to claim 5, wherein the inflammatory disease comprises gout, type II diabetes, or systemic lupus erythematosus.

7. The use of claim 5, wherein the BI8626 treats the inflammatory disease by inhibiting inflammasome activation.

8. The medicine for treating the inflammatory diseases is characterized by comprising an active ingredient BI8626 and a pharmaceutically acceptable carrier.

Technical Field

The invention relates to the technical field of biological medicines, in particular to application of HUWE1 inhibitor BI8626 in preparation of a medicine for inhibiting activation of inflammasome.

Background

Classical Inflammasomes include N L RP3, AIM2 and N L RC4 Inflammasomes, the activation of which, by recognizing different stimuli, eventually leads to activation of Caspase-1 (Caspase-1), inducing cells to produce mature interleukin 1 β (I L-1 β), interleukin 18(I L-18), activated Caspase-1 cleavable gut dermatan d (gsdmd), leading to the occurrence of cell apoptosis (inflama antibodies: mechanism of action, roll in disease, atheromics 2015ato Guo, Justin B callaw & jenp-Y Ting; Nature in liposome 21, 677-7 (patch 677-7), multiple Inflammasomes activating and related diseases, multiple inflammation related corpuscles, autoimmune disease activation and systemic inflammation related diseases, such as systemic lupus erythematosus, etc., are not reported in the preparation of drugs for inhibiting inflammatory diseases, systemic lupus erythematosus, autoimmune diseases, etc., but no effective drugs for inhibiting inflammatory corpuscles, systemic lupus erythematosus, autoimmune diseases, systemic lupus erythematosus, etc. are reported.

Disclosure of Invention

The invention aims to provide application of HUWE1 inhibitor BI8626 in preparing a medicament for inhibiting activation of inflammasome.

In order to achieve the above object, the present invention provides the following technical solutions:

the invention provides application of HUWE1 inhibitor BI8626 in preparing a medicament for inhibiting activation of inflammasome; the chemical structural formula of the BI8626 is shown as a formula I;

preferably, the inflammasome comprises N L RP3, AIM2 or N L RC 4.

Preferably, the N L RP3 is activated by lipopolysaccharide and adenosine triphosphate together, the AIM2 is activated by dsDNA, and the N L RC4 is activated by Salmonella.

The invention provides a medicament for inhibiting activation of an inflammasome, which comprises an active ingredient BI8626 and a pharmaceutically acceptable carrier.

The invention provides application of HUWE1 inhibitor BI8626 in preparation of a medicament for treating inflammatory diseases.

Preferably, the inflammatory disease includes gout, type II diabetes, or systemic lupus erythematosus.

Preferably, the BI8626 treats the inflammatory disease by inhibiting inflammasome activation.

The invention provides a medicine for treating inflammatory diseases, which comprises an active ingredient BI8626 and a pharmaceutically acceptable carrier.

The invention has the beneficial effects that the invention provides the application of HUWE1 inhibitor BI8626 in preparing the medicine for inhibiting the activation of the inflammasome, wherein the BI8626 can obviously inhibit the activation of N L RP3, AIM2 and N L RC4 inflammasome in mouse BMDM cells, obviously reduce the activation of cysteine proteinase-1 (Caspase-1) and reduce the death of cells.

Drawings

FIG. 1 is a graph comparing expression of activated caspase1P20 in mouse primary BMDM cells after treatment with BI8626 treatment and control.

Detailed Description

The invention provides application of HUWE1 inhibitor BI8626 in preparing a medicament for inhibiting activation of inflammasome; the chemical structural formula of the BI8626 is shown as a formula I; BI8626 is commercially available from conventional sources, and in the practice of the present invention, BI8626 is available from MedChemexpress as HY-120204;

in the present invention, the inflammasome comprises N L RP3, AIM2 or N L RC4, the N L RP3 is preferably activated by lipopolysaccharide and adenosine triphosphate together, the AIM2 is preferably activated by dsDNA, and the N L RC4 is preferably activated by Salmonella.

The invention provides a medicament for inhibiting activation of an inflammasome, which comprises an active ingredient BI8626 and a pharmaceutically acceptable carrier.

The invention provides application of HUWE1 inhibitor BI8626 in preparing a medicament for treating inflammatory diseases; the inflammatory diseases preferably include gout, type II diabetes or systemic lupus erythematosus, but are not limited to the above diseases; the BI8626 preferably treats inflammatory diseases by inhibiting inflammatory body activation.

Abnormal activation of N L RP3, AIM2 and N L RC4 inflamed bodies often leads to the occurrence of inflammatory and autoimmune diseases such as gout, diabetes and systemic lupus erythematosus.

The invention provides a medicine for treating inflammatory diseases, which comprises an active ingredient BI8626 and a pharmaceutically acceptable carrier.

The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

In a specific embodiment of the invention, healthy C57/B L mice were provided by Kunming animal research institute of Chinese academy of sciences [ laboratory animal license number: SYXK (Dian) K2013-0013 ].

HUWE1 inhibitor BI8626 of the present invention was purchased from MedChemexpress, Inc., cat # HY-120204.

N L RP3 inflammasome is typically activated by exogenous molecules such as gram negative bacterial cell wall components, nucleic acids, perforin, endogenous molecules such as Adenosine Triphosphate (ATP), uric acid crystals, etc. (Cassel S. L, Eisenbarth S.C., Iyer S.S., et al, The Nalp3 inflamosoma S infection for The development of silicon, Proc. Natl. Acad. Sci.USA,2008,105(26):9035-9040.Kanneganti T. D., Body-Lapepel M., Amper A., 2006, et al, Critical roll for Cryoprotein/Nalp 3 in activation of enzyme-1 in vaccine to viral infection of chemical RNA, 3648, 36281J. Biocide J. 3648).

The N L RC4 inflammasome is activated by infection with Salmonella (Salmonella) (Mariatasan S., Newton K., Monack D.M., et al. differential activation of the inflamasome by caspase-1adapt ASC and Ipaf. Nature,2004,430(6996): 213-218).

AIM2 inflammasome is activated by Francisella and double-stranded DNA (dsDNA) induction (Fernandes-Alnemrit, Yu J. -W., Juliana C., et al, The AIM2 inflama sodium criti for The initiation of inflammation to Francisella tularensis. Nat. Immunol.2010,11: 393.B ü rckst ü mmer. Baumann C., Bl ü ml S., et al, an organic proteinaceous-genetic screening AIM2 a cytoplasma DNA sensor for The expression of AIM Nat. Immunol. 266, 10: 272).

In the present invention, all the raw material components are commercially available products well known to those skilled in the art unless otherwise specified.