Application of STING stimulant and IDO1 inhibitor combined drug for antineoplastic treatment

A 1.STING, 5.STING technology, applied in the field of biomedicine

Inactive Publication Date: 2017-04-05
LIAOCHENG CITY ORIENT BIOMEDICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no literature report on the combined use of STING agonist (cyclic dinucleotide cGAMP) and IDO1 inhibitor in the treatment of tumors

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Example 1: Preparation and purchase of STING agonist cGAMP and IDO1 inhibitor 1-methyl-D-tryptophan (Indoximod)

[0016] cGAMP is catalyzed and synthesized by cyclized dinucleotide synthetase (cGAS) under activation conditions after binding to DNA according to the literature method, and the purity is above 98%. (Pingwei Li, et al., Immunity, 2013, 39(6), 1019-1031.). 1-Methyl-D-tryptophan (Indoximod) was purchased from Sigma, USA.

Embodiment 2

[0017] Example 2: Anti-tumor animal experiments of STING agonist cGAMP and IDO1 inhibitor Indoximod combined

[0018] The tumor-bearing mouse model was used to detect the inhibitory effect of cGAMP and Indoximod anti-tumor combination on the growth of subcutaneous transplanted tumors in animals and the acute toxicity to animals.

[0019] 1. Animals

[0020] Healthy male F1 mice of Kunming white hybrid Babl / c, weighing 20-25 g, were reared in groups of 10 mice / cage, divided into 16 groups in total. Purchased from Shanghai Slack Experimental Animal Co., Ltd., quality certificate number (animal certificate number: SCXK (Shanghai) 2007-0005). Raised in a clean animal room.

[0021] 2. Drugs

[0022] Indoximod was purchased from Sigma, USA, and cGAMP was prepared according to the above literature method.

[0023] Group the experimental mice into groups:

[0024] Group A, the normal group, was not inoculated with tumors, and was given the same amount of normal saline as the d...

Embodiment 3

[0070] Example 3 Acute Toxicity Study of Combination of cGAMP and Indoximod

[0071] Experimental Materials

[0072] 30 ICR mice (purchased from Shanghai Slack Experimental Animal Co., Ltd. [Experimental animal quality certificate number: SCXK (Shanghai) 2007-0005]), half male and half male, weighing 18-22 g, the animals were fed with pellet feed, free Eat and drink. cGAMP and Indoximod were prepared with saline to a concentration of 200 mg / mL solution.

[0073] experimental method

[0074] ICR mice were intraperitoneally injected with 2g / kg of cGAMP and Indoximod respectively according to body weight, and observed the toxicity and death of mice within 14 days after administration. It was found that after the mice were injected with the drug, the mice moved normally. Within 14 days after the administration, the mice did not die. On the 15th day, all the mice were sacrificed, dissected, and all organs were inspected with the naked eye, and no obvious lesions were found. ...

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PUM

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Abstract

The invention belongs to the technical field of medicine, and concretely relates to an application of a STING stimulant and IDO1 inhibitor-combined drug for antineoplastic treatment. The research shows that the IDO1 inhibitor (1-methyl-D-tryptophan) and autoimmune pathway STING (interferon stimulated protein gene) stimulant cGAMP-combined drug has antineoplastic effect, which has better antineoplastic drug effect than that of a single STING stimulant cGAMP, the animal acute toxicity test shows that the acute toxicity of the combined drug is low, The STING stimulant and the IDO1 inhibitor-combined drug can be used for antitumor drugs.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of an agonist of the key protein STING of an autoimmune signaling pathway combined with an inhibitor of indoleamine-2,3-dioxygenase 1 (IDO1) in anti-tumor. Background technique [0002] Tumor is one of the major diseases that seriously endanger human life and health. It is characterized by excessive cell proliferation and abnormal differentiation. WHO experts predict that in 2020, the incidence of cancer in the global population will reach 20 million, and the death toll will reach 12 million. Tumor will become the number one killer of human beings in this century and pose the most serious threat to human survival. The morbidity and mortality of lung cancer, colorectal cancer, gastric cancer, and liver cancer rank among the forefront of various malignant tumors. According to the statistics released by the National Cancer Registration Center (2012 China Cancer ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/7084A61K31/405A61P35/00
CPCA61K45/06A61K31/405A61K31/7084A61K2300/00
Inventor 谭相石谭瀛轩向道凤张跃茹
Owner LIAOCHENG CITY ORIENT BIOMEDICAL TECH CO LTD
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