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

Treatment of hematological malignancy with small molecule nf-kb inhibitors

A technology for multiple myeloma and lymphoma, applied in the field of the treatment of malignant hematological tumors, which can solve the problems of different biological effects and toxicity characteristics

Inactive Publication Date: 2019-12-17
纪念斯隆–凯特林癌病中心 +1
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, therapeutics targeting different NF-κB / Rel members may have different biological effects and toxicity profiles

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
  • Treatment of hematological malignancy with small molecule nf-kb inhibitors
  • Treatment of hematological malignancy with small molecule nf-kb inhibitors
  • Treatment of hematological malignancy with small molecule nf-kb inhibitors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0086] Example 1: General Synthetic Scheme

[0087] The NF-κB inhibitors of the invention may be synthesized by any suitable method known in the art or as further described below.

[0088]

[0089] Scenario 1.2

[0090]

[0091] Scenario 1.3

[0092]

[0093] Scenario 1.4

[0094]

[0095] Scenario 1.5

[0096]

[0097] Scenario 2.1

[0098]

[0099] Scenario 2.2

[0100]

[0101] Scenario 2.3

[0102]

Embodiment 2

[0103] Embodiment 2: specific compound synthetic scheme

[0104] Preparation of IT-848

[0105]

[0106] Step 1: Preparation of 2-chloro-3-(hexyloxy)phenol

[0107] A three-neck round bottom flash (reactor) with a capacity of 500 mL was equipped with a magnetic stirrer, reflux condenser and thermometer. 18-crown-6 (3.17g, 12mmol), NaI (26.98g, 180mmol), K 2 CO 3 (33.17g, 240mmol), 2-chlororesorcinol (29.91g, 200mmol), acetone (116mL) and 1-bromohexane (29.17g, 180mmol) were added to the reactor in this order. The mixture was heated with an oil bath. The oil bath temperature was set at 72°C. The temperature in the reactor reached 60°C in a stable reaction state. The mixture becomes thicker and thicker. 5 hours after the start of the reaction, 29 mL of acetone was further added to the mixture. After 9 hours the reaction was stopped and cooled to room temperature. Once the reaction mixture reached room temperature, 150 mL of deionized water and 150 mL of ethyl acetate...

Embodiment 4

[0127] Example 4: Mice, cell lines and primary cells

[0128] Cell Lines and Primary Cells

[0129] Human peripheral blood mononuclear cells (PBMC) were purified from donor blood according to accepted protocols. Mouse splenocytes are purified from mouse spleen using methods known to those skilled in the art.

[0130] Human DLBCL-derived cell lines SU-DHL4 and U2932 were obtained from the German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures (Braunschweig, Germany); MM.1S and U266 cells were obtained from ATCC; HBL1 cells were kindly provided by Dr. R.E. Davis (Houston, TX) and certified by the MD Anderson Characterized Cell Lines Core Facility . MM.1S cells were retrovirally transduced to express a fusion protein consisting of enhanced green fluorescent protein and firefly luciferase. Cell lines were grown in RPMI1640 medium supplemented with 10-20% fetal bovine serum, 1% L-glutamine, and penicillin-streptomycin in 5% CO 2 cul...

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 disclosure relates to compounds and compositions that inhibit NFKB and are useful in the treatment of hematological malignancies such as lymphoma and myeloma.The present disclosure also provides methods for inhibiting growth and proliferation of cells selected from the group consisting of lymphoma cells and myeloma cells and for the treatment of hematological malignancies using compounds and pharmaceutical compositions capable of inhibiting NF-KB.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application 62 / 439,335, filed December 27, 2016, and US Provisional Application 62 / 439,841, filed December 28, 2016; the contents of both are hereby incorporated by reference. [0003] Government funding [0004] This invention was made with government support under CA160659 awarded by the National Institutes of Health. The government has certain rights in this invention. technical field [0005] The present invention provides methods of treating hematological malignancies using compounds and pharmaceutical compositions capable of inhibiting NF-κB. Background technique [0006] NF-κB / Rel (nuclear factor κB) is a family of transcription factors including p50 / p105 (NF-κB1), p52 / p100 (NF-κB2), p65 (RelA), c-Rel and RelB. These molecules can homo- or heterodimerize and are usually sequestered in the cytoplasm by their inhibitors (IκB). When activated, IκB is degraded b...

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): A61K31/519C07D491/04
CPCA61K45/06A61K31/4045A61K31/519A61K31/69C07D491/052A61P35/00A61K2300/00A61K31/505
Inventor 约翰内斯·扎克热夫斯基刘秀枝S·吴
Owner 纪念斯隆–凯特林癌病中心
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