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Anti-tumor pharmaceutical composition containing EZH2 inhibitor and SCD1 inhibitor and application of anti-tumor pharmaceutical composition

An anti-tumor effect and inhibitor technology, applied in the field of medicine, can solve problems such as poor activity, and achieve the effect of enhancing curative effect, good clinical application prospects, and enhancing anti-tumor effect.

Active Publication Date: 2022-03-15
PEKING UNIV THIRD HOSPITAL
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AI Technical Summary

Problems solved by technology

[0008] The purpose of the present invention is to solve the problem of poor activity of EZH2 inhibitors on solid tumors, and to provide a pharmaceutical composition comprising EZH2 inhibitors and SCD1 inhibitors that can enhance the anti-tumor effect of EZH2 inhibitors, which is clinically safe. Provide a new idea for the effective, convenient and economical use of EZH2 inhibitors in the treatment of solid tumors

Method used

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  • Anti-tumor pharmaceutical composition containing EZH2 inhibitor and SCD1 inhibitor and application of anti-tumor pharmaceutical composition
  • Anti-tumor pharmaceutical composition containing EZH2 inhibitor and SCD1 inhibitor and application of anti-tumor pharmaceutical composition

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Experimental program
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Embodiment

[0052] 1. A variety of solid tumor cell lines are less sensitive to the EZH2 inhibitor GSK126

[0053] To accurately assess the responsiveness of solid tumor cells to EZH2 inhibitors, the IncuCyte Live-Cell Analysis System detected the effects of different concentrations of GSK126 on the proliferation of melanoma cell B16F10 and liver cancer cells Huh7 and SMMC-7721. The results showed that GSK126 inhibited cell proliferation in a dose-dependent manner, while the effect of a higher concentration of 10 μM GSK126 was not good ( figure 1 A).

[0054] Under the same conditions, the results of CCK-8 cell proliferation experiments showed that the proliferation of hematological tumor cells Daudi and THP-1 was significantly inhibited after being treated with 10μM GSK126 for 24h and 48h. Especially the Burkitt lymphoma cell Daudi is already very sensitive to 1μM GSK126 ( figure 1 B). Consistent with other studies, we found that solid tumor cell lines are generally insensitive to E...

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Abstract

The invention belongs to the field of medicine, and provides a pharmaceutical composition for enhancing the anti-tumor effect of an EZH2 inhibitor, the pharmaceutical composition comprises the EZH2 inhibitor and an SCD1 inhibitor, and the SCD1 inhibitor enhances the anti-solid tumor effect of the EZH2 inhibitor. The invention also provides a related preparation of the pharmaceutical composition and application of the pharmaceutical composition in preparation of antitumor drugs. Experimental results show that the EZH2 inhibitor GSK126 and the SCD1 inhibitor MF-438 are combined for treating B16F10 and SMMC7721 cells, and it is found that the inhibition effect of the GSK126 on cell proliferation can be obviously enhanced by combining the EZH2 inhibitor GSK126 and the SCD1 inhibitor MF-438. The invention provides a new thought for safely, effectively, conveniently and economically treating solid tumors by using the EZH2 inhibitor clinically, and has a good clinical application prospect.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to an antitumor drug composition comprising an EZH2 inhibitor and an SCD1 inhibitor and its application in preparing antitumor drugs. Background technique [0002] Zeste gene enhancer homolog 2 (Enhancer of zeste homolog 2, EZH2) is the catalytic subunit of polycomb repressive complex 2 (polycomb repressive complex 2, PRC2), which plays the role of histone methyltransferase. Abnormalities of EZH2 exist in many diseases (such as tumors), and multiple evidences show that EZH2 is related to the occurrence and progression of various cancers and poor prognosis. EZH2 overexpression is mainly seen in solid tumors, including prostate cancer, breast cancer, bladder cancer, endometrial cancer, and melanoma, etc. High levels of EZH2 expression are often associated with high aggressiveness, tumor progression, and poor survival Clinical outcomes are associated with prognosis. [0003] Unlik...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/501A61P35/00A61K31/496
CPCA61K45/06A61K31/496A61K31/501A61P35/00A61K2300/00
Inventor 薛丽香郭正阳张腾瑞王艳孙艳龚月卿
Owner PEKING UNIV THIRD HOSPITAL
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