Purpose of compound for preparing medicine used for treating tumor

A technology of compounds and uses, which is applied in the field of preparing drugs for treating tumors, and can solve problems such as the lack of small molecule inhibitors

Active Publication Date: 2021-01-05
WEIFANG MEDICAL UNIV
View PDF2 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite this, there are currently no small molecule inhibitors of JMJD1C

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Purpose of compound for preparing medicine used for treating tumor
  • Purpose of compound for preparing medicine used for treating tumor
  • Purpose of compound for preparing medicine used for treating tumor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047]Identification of potential JMJD1C small molecule modulator JDI-10 (formula a1). Such asfigure 1 description.

[0048]Among the potential JMJD1C modulators obtained through virtual screening from nearly 200,000 natural components and active ingredients of traditional Chinese medicine, the compound JDI-10 (formula a1) with the highest virtual screening docking score was selected.

[0049]Such asfigure 1 As shown, the virtual screening molecular docking shows that JDI-10 (formula a1) can interact with JMJD1C. Among them, the above figure shows the two-dimensional model of the interaction between JDI-10 (the molecule shown in the middle stick model) and the key amino acids in the catalytic domain of the JMJD1C protein; the bottom figure shows the JDI-10 (shown in the middle stick model) The three-dimensional model of the interaction between the molecule) and the key amino acids in the catalytic domain of the JMJD1C protein.

Embodiment 2

[0051]The cell proliferation experiment was used to detect the inhibition of JDI-10 on a variety of hematopoietic malignant cell lines.

[0052]The cell lines used include: MV4-11, SEM, MOLM-13, THP-1, KASUMI-1, HL-60, K562, JURKAT, KG-1, MUTZ-3, MUTZ-8, NB-4, OCI -AML5. These cell lines are derived from the German National Cell Institute (Leibniz Institute DSMZ-German Collection of Microorganisms and CellCultures). The cells were cultured at 37°C and 5% carbon dioxide according to the culture method provided on the DSMZ website (https: / / www.dsmz.de / catalogues / catalogue-human-and-animal-cell-lines.html). The medium (RPMI1640 or α-MEM) and fetal calf serum were from Thermal Fisher.

[0053]Cells were seeded in a 96-well plate with a V bottom at a concentration of 30,000 / ml in 100 microliters to ensure that the cells maintain exponential growth during the 6-day culture. 24 hours after the inoculation, JDI-10 (dissolved in DMSO) of different concentrations (25, 10, 5, 2.5, 1, 0.5, 0.25, 0.1 ...

Embodiment 3

[0058]The colony formation experiment was used to detect the effect of JDI-10 on various malignant cell lines of hematopoietic system, primary leukemia cells, and cord blood cells from healthy donors.

[0059]MLL ectopic leukemia cell lines MV4-11 (2000 / ml), MOLM-13 (1000 / ml), THP-1 (2000 / ml), etc. were inoculated into methylcellulose semi-solid medium (Cat. No. H4100, Stemcell Technologies) Company, USA), the treatment group uses 10μM JDI-10, and the control group uses equal volume of DMSO to ensure that the total volume of DMSO does not exceed 0.1%. After 8-10 days of treatment, the results of colony formation were detected and the number of clones was calculated.

[0060]Leukemia cells with normal karyotype (P91) or MLL-ELL fusion gene (P93) or AML1-ETO fusion gene (P94) from patient samples were inoculated into methylcellulose semi-solid medium (Cat. No. H4434, Stemcell Technologies, USA), the treatment group uses 10μM JDI-10, and the control group uses equal volume of DMSO to ensure ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to a compound and a purpose of the compound for preparing a medicine used for treating a tumor. The above technical scheme can consider that the invention authenticates a micromolecule conditioning agent capable of aiming at JMJD1C, and the JMJD1C micromolecule conditioning agent which takes JDI-10 as a representative can selectively kill leukemia cells and leukemia stem cells but does not affect normal hematopoiesis.

Description

Technical field[0001]The present invention relates to the field of biomedicine, in particular to the use of a compound in the preparation of drugs for treating tumors.Background technique[0002]Acute leukemia (AL) is the type of leukemia with the highest incidence among adults in China, and the prognosis of its subtypes varies greatly. Mixed lineage leukemia rearrangement (MLLr) accounts for about 10% of AL, and indicates a moderate or poor prognosis. Currently, the most promising strategy for MLLr AL is targeted therapy.[0003]A variety of chromatin-related proteins are essential for the maintenance of MLLr AL, such as histone H3K79 methyltransferase DOT1L, histone H3K27 methyltransferase component PRC2 complex, histone demethylase LSD1 (KDM1A ), KDM4C, histone modification binding protein BRD4, RNF20, MENIN, LEDGF, CBX8. These MLLr AL maintenance essential proteins are potential drug targets of MLLr AL. Small molecule inhibitors for some of these proteins have been successfully deve...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4725A61P35/00A61P35/04
CPCA61K31/4725A61P35/00A61P35/04
Inventor 徐鑫胡振波
Owner WEIFANG MEDICAL UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap