| Project/Area Number |
19K23987
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0903:Organ-based internal medicine and related fields
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2019-08-30 – 2021-03-31
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| Project Status |
Discontinued (Fiscal Year 2020)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | pulmonary hypertension / Emetine / Drug development / 薬理学一般 / 循環器内科学 |
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| Outline of Research at the Start |
Pulmonary arterial hypertension (PAH) is a fatal disease with a 20% 5-years survival rate without treatment. Importantly, early diagnosis method is very rare in pulmonary hypertension, which is confirmed at the mild stage except in special cases such as family onset, and usually the diagnosis of pulmonary hypertension is confirmed after finally progressed. The purpose of this study is to discover new drugs for pulmonary hypertension with antiproliferative effects on VSMCs from patients with PAH by drug repositioning of existing drugs.
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| Outline of Annual Research Achievements |
To develop new drugs for the treatment of pulmonary hypertension (PH) with antiproliferative effects on VSMCs from patients with PAH by drug repositioning of existing drugs, we have chemically synthesized emetine analogs and check antiproliferative activity of the analogs in pulmonary artery smooth muscle cells (PASMCs) from PAH patients (PAH-PASMCs). We have developed 16 analogs of emetine and based on inhibitory effects on PAH-PASMC proliferation, and selected an analog as GMP-emetine for further study in vitro. GMP-emetine showed similar antiproliferative effects on PAH-PASMCs like parent emetine.
To identify the specific target protein of GMP-emetine, we have isolated total RNA from PAH-PASMCs after treatment with or without GMP-emetine. Next, we will perform microarray to see the changes of gene expressions in response to GMP-emetine and finally we will identify the specific target protein of GMP-emetine.
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