| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| 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.
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