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AssigneeFudan University
InventorsXiangshi Tan, Tiejun Li, Qiming Xu, Jie Pan, Yaocheng Rui, Hao Cheng, Yuefan Zhang
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The present invention belongs to the field of medicine technology, particularly relating to an application of cyclic dinucleotide (cGAMP) in tumor treatment. Researches carried out in the present invention show that, cGAMP can inhibit growth of many types of tumor cells, with remarkable anti-tumor effect, thus, it can be used in preparation of anti-tumor drugs; and the prepared anti-tumor drugs have low toxicity and favorable effect. Proved by a subcutaneous tumor model in nude mice, cGAMP has a remarkable inhibition effect on tumors of human gastric carcinoma cell line MNK-45, human lung adenocarcinoma cell line A549, human colorectal carcinoma cell line Lovo, human hepatocellular carcinoma cell line SMMC-7721, human prostatic carcinoma cell line PC-3 and human pancreatic carcinoma cell SW1990, which are subcutaneously implanted in nude mice, and also proved by animal acute toxicity experiment. cGAMP has a relatively low acute toxicity, therefore and may be used for preparing anti-tumor drugs.
A method for treating a malignant tumor in a subject in need thereof comprising administering to the subject a composition consisting essentially of cGAMP.
A method for inhibiting tumor growth comprising contacting tumor cells with a composition consisting essentially of cGAMP.
A method for treating a malignant tumor in a subject in need thereof comprising administering to the subject a composition consisting essentially of an anti-tumor drug and a pharmaceutically acceptable carrier, wherein the anti-tumor drug comprises cGAMP, and the malignant tumor is a hepatocellular carcinoma or a gastric carcinoma.
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Carbohydrates; Sugars; Derivatives thereof: compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide,…
Antineoplastic agents
Having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides: containing six-membered rings with nitrogen as a ring hetero atom
Containing six-membered rings with nitrogen as a ring hetero atom: containing condensed or non-condensed pyrimidines
About 8 years 6 months of term left · ends 20 Apr 2035 (estimated)
The present invention belongs to the field of medicine technology, and more particularly, relates to an application of cyclic dinucleotide (cGAMP) in anti-tumor field and in preparation of anti-tumor drugs.
Tumor is one of the major diseases that seriously endanger human life and health, and it is the abnormal proliferation and differentiation of cells. Experts of WHO predict that in 2020 the global population of cancer incidence will reach 20 million, the death toll will reach 12 million, and the cancer will become the number one killer of human beings in this century and the most serious threat to human survival. Incidence and mortality rates of lung cancer, colorectal cancer, gastric cancer and liver cancer rank in the top five positions among all types of malignant tumors.
According to data from “2012 Chinese Cancer Registry Annual Report”, released by the National Cancer Registry, new tumor cases for each year is about 3,120,000, an average of 8, 550 people per day, 6 people per minute in the country are diagnosed with cancer. Lung cancer, gastric cancer, colorectal cancer, liver cancer and esophageal cancer, are ranking in the top five in the national malignant tumor incidence. With the increase of incidence and mortality of malignant tumor, the demand for treatment of malignant tumor is increasing.
cGAMP (cyclized GMP-AMP), with purity above 98%, was catalytically synthesized by cGMP-AMP dinucleotide synthetase (cGAS), after bonding DNAs under activation conditions, according to the literature method (Pingwei Li, et al., Immunity, 2013, 39(6), 1019-1031).
Anti-tumor effect of cGAMP (cyclized GMP-AMP) was detected by employing a tumor-bearing mouse model to test inhibition effect of cGAMP on subcutaneously transplanted tumor.
The tested drug: Name: cGAMP Character: white powders Solvent: brine Preparation method: the test drug was dissolved to obtain a solution having a required concentration with brine before use Concentration of the tested drug: 1 mg/ml and 4 mg/ml.