| Project/Area Number |
18K16092
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 54010:Hematology and medical oncology-related
|
|---|
| Research Institution | Kumamoto University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | 多発性骨髄腫 / 形質細胞 / プリン代謝経路阻害 / AMPD1 |
|---|
| Outline of Final Research Achievements |
We identified AMPD1, a purine metabolic enzyme that catalyzes AMP into IMP, is specifically expressed in normal plasma cells and multiple myeloma cells using public available gene expression data sets and patient derived samples. AMPD1 inhibitors inhibited the proliferation of myeloma cells in vitro, leading to myeloma cell death. AMPD1 inhibitors did not affect the survival of normal lymphocytes, proving that AMPD1 inhibition may work specifically on myeloma cells. We attempt to develop a novel AMPD1 inhibitor based on pre-existing AMPD1 inhibitors. As a result we succeeded in developing several AMPD1 inhibitors that were more effective compared to the pre-existing inhibitors.
|
| Academic Significance and Societal Importance of the Research Achievements |
多発性骨髄腫は高齢化社会に伴い増加中の治癒が非常に困難な造血器腫瘍であり、骨髄腫の治癒のためには既存の治療薬とは異なる作用機序の治療戦略が望まれている。今回、我々はAMPD1という骨髄腫細胞に特異的に発現する分子が新たな治療標的となり得ることを見出すことができ、既存のAMPD1阻害剤よりも活性の高い化合物を同定することができた。今後、AMPD1阻害が多発性骨髄腫の新たな治療選択肢となることが期待される。
|
