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Application of small molecule inhibitor of methane sulfonamides in preparation of antitumor drugs

A technology of small molecule inhibitors and anti-tumor drugs, applied in the field of biomedicine, can solve problems such as reducing the intracellular activation level of PI3K, and achieve good anti-tumor activity and good anti-cancer effect

Inactive Publication Date: 2018-10-12
JILIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although small molecule inhibitors targeting PI3K have entered preclinical and clinical trials, there is still a lot of room for improvement in the development and research of PI3K inhibitors. We need to rationally design and optimize new small molecules targeting PI3K Compounds, these small molecular compounds can effectively reduce the intracellular activation level of PI3K and achieve the purpose of specifically killing tumors

Method used

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  • Application of small molecule inhibitor of methane sulfonamides in preparation of antitumor drugs
  • Application of small molecule inhibitor of methane sulfonamides in preparation of antitumor drugs
  • Application of small molecule inhibitor of methane sulfonamides in preparation of antitumor drugs

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Experimental program
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Embodiment 1

[0024] The configuration of embodiment 1 medicine

[0025] The solid powder of methanesulfonamide small molecule inhibitor DHW-5 (formed by Professor Song Hongrui of Shenyang Pharmaceutical University) was dissolved with an appropriate amount of dimethyl sulfoxide (DMSO) to obtain a drug solution with a concentration of 5 mM, and then incubated with 1640 base (purchased from Gibco Company) to dilute the drug 100 times to obtain a 50 μM drug solution, which was used as the initial screening concentration of the drug, and other concentrations were carried out with 1640 medium (purchased from Gibco Company) on the basis of this concentration. Dilution of smaller concentrations.

Embodiment 2

[0026] Recovery, cultivation and subculture of embodiment 2 cells

[0027] After taking out the cryopreservation tube containing BT549 cells from the liquid nitrogen tank, immediately put it into a beaker filled with warm water at 37°C, and after the cell suspension in the cryopreservation tube melts, quickly transfer the cryopreservation tube to the ultra-clean working place. Taichung, then slowly add the thawed cell suspension into a centrifuge tube filled with phosphate buffered saline (PBS), and centrifuge at 1500rpm for 3min. The supernatant after centrifugation was discarded, and the cell pellet was resuspended with 1 mL of 1640 medium (purchased from Gibco) containing 10% (V / V) fetal bovine serum, and the resuspended cells were added to 10 mL of 1640 medium containing culture medium (purchased from Gibco) in a 10cm-diameter dish, and then the cells were placed at 37°C with 5% (V / V) CO 2 cultured in a cell culture incubator. When the cells grow to a density of 80%-90%,...

Embodiment 3

[0028] Example 3 Preliminary Screening and IC of Anticancer Activity of Methanesulfonamide Small Molecule Inhibitors 50 value detection

[0029] Anticancer activity and IC 50 Values ​​are detected using the MTT method.

[0030] Detection principle: MTT method, also known as MTT colorimetric method, is a method for detecting cell survival and growth. MTT can be reduced to purple formazan particles by the succinate dehydrogenase contained in the mitochondria of living cells, which cannot be dissolved in water, but the mitochondria of dead cells cannot restore it, and DMSO can dissolve formazan For particles, use a microplate reader to measure the absorbance value at a wavelength of 492nm, that is, the OD value, which can indirectly reflect the number of cells. Therefore, we can evaluate the survival and death of cells through the change of the reaction color.

[0031] Specific steps:

[0032] (1) First digest and collect the adherent cells obtained in Example 2, count the c...

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Abstract

The invention discloses application of a small molecule inhibitor DHW-5 of methane sulfonamides in preparation of antitumor drugs, and belongs to the technical field of biological medicine. Accordingto the application, a drug DHW-5 which can effectively inhibit the growth of tumor cells is screened out from small molecule inhibitor libraries of the methane sulfonamides, and can effectively inhibit the proliferation of cervical cancer hela cells, breast cancer BT549 cells, non-small cell lung cancer A549 cells, ovarian cancer SKOV-3 cells and gastric cancer cells SGC-7901, the semi-inhibitoryconcentration are all lower than 9.0 uM, and particularly, the inhibition effect on the breast cancer BT549 cells is the best. The inhibitor can target phosphoinositide 3kinase (PI3K), block the conduction of PI3K signaling pathways, and trigger cycle arrest and endogenous pathways mediated by mitochondria so as to induce apoptosis of the tumor cells. The inhibitor can be used for preparing the antitumor drugs and provides a new idea and mechanism for the research and development of antitumor small molecule drugs of kinase inhibitors.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of a methanesulfonamide small molecule inhibitor DHW-5 in the preparation of antitumor drugs. Background technique [0002] Tumor is an important killer that threatens human health and life, and its morbidity and mortality rate rank first among all kinds of diseases. At present, the commonly used clinical treatment methods include surgery, chemotherapy, radiotherapy and biological therapy, but most of the drugs used in the clinical treatment of tumors have a series of toxic and side effects such as very strong immunosuppression and damage to systemic organs. Therefore, there is an urgent need to research and develop new tumor-specific drugs. [0003] Phosphoinositide-3-kinase (Phosphoinositide 3-kinase, PI3K) is a phosphokinase, which can integrate growth factors, cytokines and other signals in the environment and convert them into intracellular s...

Claims

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Application Information

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IPC IPC(8): A61K31/517A61P35/00
CPCA61K31/517A61P35/00
Inventor 施维宋宏瑞李蒙蒙柴少蒙
Owner JILIN UNIV
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