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Applications of dehydro-alpha-lapachone in serving as indoleamine 2,3-dioxygenase-1 inhibitor

A technology of dioxygenase and inhibitors, applied in the field of application of dehydroα-lapachone as an indoleamine 2,3-dioxygenase-1 inhibitor, can solve the problem that the number of IDO1 inhibitors is small and the experimental Room or clinical effects need to be improved, etc.

Inactive Publication Date: 2016-11-09
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the overall number of IDO1 inhibitors is still small, and the laboratory or clinical effects still need to be improved

Method used

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  • Applications of dehydro-alpha-lapachone in serving as indoleamine 2,3-dioxygenase-1 inhibitor
  • Applications of dehydro-alpha-lapachone in serving as indoleamine 2,3-dioxygenase-1 inhibitor

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Embodiment Construction

[0015] The present invention will now be further explained in conjunction with the following experiments and accompanying drawings. It should be noted that these experimental examples and accompanying drawings should not be construed as limiting the present invention.

[0016] Kynurenine standard curve drawing

[0017] 1. Standard medium (200 μL): 20 μL of 0.5M potassium phosphate buffer (pH 6.5), with a final concentration of 50 mM; 20 μL of 0.2M ascorbic acid, with a final concentration of 20 mM; 4 μL of 0.5 mM methylene blue, with a final concentration of 10 μM; 4 μL of 5 mg / ml catalase to a final concentration of 100 μg / ml; 132 μL of dd-H 2 O; 20 μL of kynurenine solution with final concentrations of 0, 1, 5, 7.5, 10, 25, 50, 75 and 100 mM.

[0018] 2. After adding 40μL of 1M NaOH solution, centrifuge the medium (11,500rpm, 4°C, 15min).

[0019] 3. Transfer 200 μL of the supernatant to a 96-well microtiter plate and measure the fluorescence intensity (λex 360nm, λem480nm...

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Abstract

The invention provides applications of a natural product, namely, dehydro-alpha-lapachone or pharmaceutically acceptable salt of dehydro-alpha-lapachone in serving as an indoleamine 2,3-dioxygenase-1 (IDO1) inhibitor, namely, the inhibiting effect of dehydro-alpha-lapachone for indoleamine 2,3-dioxygenase-1, dehydro-alpha-lapachone has the function of hindering and / or destroying the acceleration effect of IDO1 in the generation and development processes of diseases, and thus good prospects are provided for treating IDO1-mediated diseases.

Description

technical field [0001] The present invention relates to the new use of dehydro-alpha-lapachone (dehydro-alpha-lapachone) as indoleamine 2,3-dioxygenase-1 (IDO1) and its application in the preparation and treatment of diseases mediated by IDO1 . Background technique [0002] Indoleamine 2,3-dioxygenase-1 [EC 1.13.11.17] (IDO1) is an intracellular, monomeric heme-containing protein that catalyzes the catabolism of l-tryptophan (Trp) into canine The first step of the uridine pathway. The IDO1 metabolite, N-formylkynurenine, is further metabolized into other bioactive molecules. IDO1 is expressed in multiple tissues, including lung, small intestine, placenta, spleen and central nervous system. IDO1 can be expressed in many cell types stimulated by inflammatory cytokines (such as interferon gamma, Escherichia coli endotoxin and tumor necrosis factor-α, etc.). IDO1 is also expressed in host antigen-presenting cells (APCs), monocyte-macrophages, and tumor cells. [0003] IDO1 ...

Claims

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Application Information

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IPC IPC(8): A61K31/352A61P35/00A61P25/18A61P25/16A61P25/28A61P27/12A61P9/00
CPCA61K31/352
Inventor 李庆王忠
Owner SUN YAT SEN UNIV
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