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Combined use of USP2 and HSP90 inhibitors to inhibit the growth of ERBB2-positive breast cancer

An inhibitor, breast cancer technology, applied in the field of medicine, can solve problems such as unclear mechanisms of ubiquitination and degradation

Active Publication Date: 2022-02-11
DALIAN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the mechanism of regulation of ErbB2 ubiquitination and degradation during combination therapy is not clear

Method used

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  • Combined use of USP2 and HSP90 inhibitors to inhibit the growth of ERBB2-positive breast cancer
  • Combined use of USP2 and HSP90 inhibitors to inhibit the growth of ERBB2-positive breast cancer
  • Combined use of USP2 and HSP90 inhibitors to inhibit the growth of ERBB2-positive breast cancer

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Embodiment Construction

[0030] The technical terms used in the present invention have the following meanings:

[0031] "ErbB2" is epidermal growth factor receptor 2, a member of the receptor tyrosine kinase (ErbB) family.

[0032] "USP2" is ubiquitin specific protease 2 (Ubiquitin specific protease 2), which is a deubiquitinating enzyme.

[0033] "HSP90" is heat shock protein 90 (heatshockprotein90), which is a molecular chaperone protein.

[0034] "ML364" is a potent known USP2 inhibitor with the following structural formula:

[0035]

[0036] "17-AAG" is Tanespimycin (Tanespimycin), which is an effective known HSP90 inhibitor, and its structural formula is as follows:

[0037]

[0038]"Ganetespib" is 3-(2,4-dihydroxy-5-isopropylphenyl)-4-(1-methylindol-5-yl)-5-hydroxy-4H-1,2,4- Triazoles, which are potent known HSP90 inhibitors, have the following structural formula:

[0039]

[0040] "PU-H71" is a potent known HSP90 inhibitor with the following structural formula:

[0041]

[0042...

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Abstract

The invention relates to the combined use of USP2 and HSP90 inhibitors to inhibit the growth of ErbB2 positive breast cancer. Specifically, the present invention discloses a pharmaceutical composition for preventing or treating ErbB2-positive breast cancer or inhibiting the proliferation of ErbB2-positive breast cancer cells, which comprises: (1) USP2 inhibitors and HSP90 inhibitors as active ingredients; and (2) A pharmaceutically acceptable carrier. The invention also discloses the use of the USP2 inhibitor and the HSP90 inhibitor in the preparation of drugs for preventing or treating ErbB2-positive breast cancer or inhibiting the proliferation of ErbB2-positive breast cancer cells.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a new application of USP2 and HSP90 inhibitors used in combination as a drug for treating ErbB2-positive breast cancer. Background technique [0002] Breast cancer is a malignant tumor with high morbidity and mortality occurring in breast epithelial tissue. The global incidence of breast cancer has been on the rise since the late 1970s, and has become a major public health problem in the current society. [0003] According to the expression difference of tyrosine kinase receptor ErbB2 (Her2), estrogen receptor (ER) and progesterone receptor (PR), breast cancer is usually divided into ErbB2 positive, ER positive and triple negative breast cancer. Of these, ErbB2-positive breast cancers account for 20-30% and generally have a relatively poor prognosis (1). Overexpression of ErbB2 can promote the formation of its dimer and the activation of kinase function, overactivate a series ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/06A61K31/395A61K31/426A61P35/00
CPCA61K45/06A61K31/395A61K31/426A61P35/00A61K2300/00
Inventor 刘晗张金瑞刘书言张迎秋
Owner DALIAN MEDICAL UNIVERSITY
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