Development of new therapeutic approach for multiple myeloma targeted against biological properties of bone marrow microenvironment

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591409
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Saitama Medical University
• Principal Investigator: KIZAKI Masahiro 埼玉医科大学, 医学部, 教授 (20161432)
• Co-Investigator(Renkei-kenkyūsha): OKUDA Akihiko 埼玉医科大学, 医学部, 教授 (60201993)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 多発性骨髄腫 / 分子標的療法 / 骨髄微小環境 / 細胞死 / NF-κB

Outline of Final Research Achievements

In the present study, new NF-κB inhibitor TM-233 was synthesized from natural compound 1'-acetoxychavicol acetate (ACA) having NF-κB inhibitory activity. TM-233 has more potent NF-κB inhibitory activity than that of ACA and induced cell death of myeloma cells via production of reactive oxygen species (ROS). TM-233 phosphorylated JAK2 and STAT3 and obstructed the shift to a nucleus of NF-κB p65. In addition, TM-233 induced cell death of bortezomib-resistant myeloma cells through inhibition of β-ring β1, β2, and β5 in the proteasome. TM-233 may become the new therapeutic agent for the multiple myeloma having potent NF-κB inhibitory activity in the bone marrow microenvironment.

Free Research Field

医歯薬学