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Uses of glutaminase inhibitor and Dyrk1B inhibitor for treatments of solid tumors

A technology of glutaminase and inhibitors, which is applied in the field of glutaminase inhibitors and Dyrk1B inhibitors for the treatment of solid tumors, and can solve the problem of not being able to fully inhibit the proliferation of cancer cells

Active Publication Date: 2020-05-19
BEIGENE BEIJING CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, CB-839 did not sufficiently inhibit the proliferation of cancer cells carrying Keap1 / Nrf2 mutations

Method used

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  • Uses of glutaminase inhibitor and Dyrk1B inhibitor for treatments of solid tumors
  • Uses of glutaminase inhibitor and Dyrk1B inhibitor for treatments of solid tumors
  • Uses of glutaminase inhibitor and Dyrk1B inhibitor for treatments of solid tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] 1. Test method:

[0050] cell culture

[0051] A549, H460, U251, H2122, H1975 cells were cultured in RPMI1640 medium containing 10% fetal bovine serum (FBS) and 1% penicillin / streptomycin. When the cells cover about 80% of the bottom of the culture dish, divide the plate, digest with 0.05% ttypsin-EDTA, neutralize with the same volume of medium, then centrifuge at 800 rpm for 3 minutes, collect the bottom cells, add the medium to resuspend and follow The experiment needs to be cultured in separate plates. If counting is required, plate preparation experiments should be carried out as required after counting. The cells were cultured in a 37°C incubator containing 5% carbon dioxide, and sterilized double-distilled water was placed at the bottom to maintain the humidity of the incubator.

[0052] Cell Proliferation Assay

[0053] On the first day, 1500 A549, H460, U251, H2122 or H1975 cells were plated per well in a 96-well plate. The next day, after the cells ad...

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Abstract

The present invention discloses a combination of a glutaminase inhibitor and a Dyrk1B inhibitor for treatments of Keap1 / Nrf2 mutation related cancers which further express DYRK1B gene.

Description

technical field [0001] The present invention relates to combinations comprising a Glutaminase inhibitor and a Dyrk1B inhibitor for use in the treatment of solid tumors. [0002] Background of the invention [0003] The KEAP1 / NRF2 (Kelch-like ECH-associated protein 1 / nuclear factorerythroid-defived 2-like 2) pathway is a key system for cells to resist oxidative stress and detoxify. In lung adenocarcinoma, Keap1 is the third most frequently mutated gene, accounting for about 10-15%, and Nrf2 gene is also mutated, accounting for about 5%. Keap1 / Nrf2 mutations will lead to activation of Nrf2 gene, and continuous activation of Nrf2 Genes can lead to a higher degree of malignancy in cancer cells, and are more likely to develop resistance to radiotherapy and chemotherapy, and many studies have found that cancer patients with Keap1 / Nrf2 gene mutations have a worse prognosis and shorter survival time. In non-small cell lung cancer, mutations in Keap1 and Nrf2 genes are associated wit...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/506A61K31/501A61P35/00
CPCA61K45/06A61K31/506A61K31/501A61P35/00A61K2300/00
Inventor 栾旭东孙毅
Owner BEIGENE BEIJING CO LTD
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