Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Application of pharmaceutical composition in preparation of drug for treating acute myeloid leukemia (AML)

A composition and leukemia technology, applied in the fields of medicinal chemistry and cell biology, can solve the problems of high recurrence rate, low long-term disease-free survival rate, and no related reports

Inactive Publication Date: 2020-01-17
ZHEJIANG UNIV
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the high recurrence rate and low long-term disease-free survival rate of AML, in order to effectively improve the prognosis of AML patients, it is imperative to develop new AML therapeutic drugs with high efficiency and low toxicity.
U.S. Patent (application number: 62112937) announced the molecular formula of a specific activity inhibitor R162 of glutamate dehydrogenase 1 (GLUD1). R162 can inhibit the proliferation of various solid tumor cells and leukemia cells, but the combination of R162 There is no relevant report on the research of other chemotherapeutic drugs

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
  • Application of pharmaceutical composition in preparation of drug for treating acute myeloid leukemia (AML)
  • Application of pharmaceutical composition in preparation of drug for treating acute myeloid leukemia (AML)
  • Application of pharmaceutical composition in preparation of drug for treating acute myeloid leukemia (AML)

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1: Effect of R162 on proliferation of AML cell lines

[0023] Take the AML cell lines THP-1, HL-60, Molm-13, and NB4 in the logarithmic growth phase and count them by centrifugation, and count them at 1×10 5The cells / well density were planted in 6-well plates, the complete medium was used as a blank control, and R-162 was added to the experimental group to a final concentration of 5, 10, 15, 20, 25, 30, 35 μM. On the 7th day of cell seeding, the cells were blown evenly and transferred into 96-well plates, four wells in each group, 100 μl per well, and 10 μl of CCK8 solution was added, 37 ° C, 5% CO 2 After incubation for 2 h, the absorbance (OD) was measured at a wavelength of 450 nm with a microplate reader. The OD of the experimental group / OD of the control group was used as an index to evaluate the cell viability.

[0024] The results of research on the inhibition of R162 on AML cell activity showed that R162 could inhibit the activity of THP-1, HL-60, Molm...

Embodiment 2

[0025] Example 2: In Vitro Study of Compositions for Treating AML

[0026] Obtain primary AML cells from newly diagnosed AML patients, add IMDM medium containing 10% fetal bovine serum, and culture at 37°C, 5% CO 2 cultured in an incubator. In the study of AML primary cells, the concentration of cytarabine in the composition was 0, 2, 4, 8, 16 μM, and the concentration of R162 was 20 μM. The experiment was divided into single use cytarabine group and cytarabine + R162 group . Place primary AML cells in a 6-well plate, 1×10 5 pcs / hole. After 48 hours of drug treatment, 100 μl of cells were inoculated into a 96-well plate, 10 μl of CCK-8 assay solution was added to each well, and incubated at 37°C for another 2 hours, the absorbance was measured by reading the plate at a wavelength of 450 nm, and each well was calculated. IC50 of group cells to cytarabine.

[0027] The results of primary cell experiments in 3 newly diagnosed AML patients showed that R162 can increase the se...

Embodiment 3

[0030] Example 3: In Vivo Study of Compositions for Treatment of AML

[0031] Female B-NSGTM (NOD-Prkdcscid II2rgtm1 / Bcgen) mice (6-8 weeks old) were used for AML modeling, and the tail vein was inoculated with 1×10 6 Molm-13-luc cells. D-luciferin (250 mg / kg) was injected intraperitoneally and imaged using the IVIS Lumina LT system. Before the treatment, the mice were randomly divided into four groups, namely the control group, the single cytarabine group, the single R162 group, and the combination group. Mice were observed and weighed daily, and leukemic burden was assessed every 7 days by bioluminescent imaging. Mice were treated with 20 mg / kg cytarabine, 20 mg / kg R162 in the composition. Cytarabine was diluted to 25 mg / mL in PBS and stored at -20°C. R162 was dissolved in DMSO to 100 mg / ml, and stored at -20°C in the dark. Cytarabine was administered daily by intravenous injection and R162 by intraperitoneal injection starting from day 8 after transplantation. In the ...

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 provides application of a pharmaceutical composition in preparation of a drug for treating acute myeloid leukemia (AML). The compound consists of a compound R162 (2-allyl-1-hydroxy-9,10-anthraquinone) and cytarabine, wherein the molar ratio of cytarabine to the compound R162 is (1:0.8)-(1:10). The provided composition can improve the capacity for inhibiting AML cell proliferation.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry and cell biology, and relates to the application of a pharmaceutical composition in the preparation of a drug for treating acute myeloid leukemia, in particular to the application of compound R162 combined with cytarabine in the preparation of a drug for treating acute myeloid leukemia. Background technique [0002] Tumor is one of the important diseases that endanger human health. According to the 2016 Global Burden of Disease Study (GBD) published in the "Lancet" magazine, 89.274 million people die from malignant tumors worldwide every year. Malignant tumors have become the second leading cause of death after cardiovascular and cerebrovascular diseases. From 2006 to 2016, the number of cancer deaths increased by 17.8% (see literature 1: Disease, G.B.D., I. Injury, and C. Prevalence, Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injur...

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
IPC IPC(8): A61K31/122A61K31/7068A61P35/02
CPCA61K31/122A61K31/7068A61P35/02A61K2300/00
Inventor 金洁马志新王敬瀚叶文乐
Owner ZHEJIANG UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com