Development and optimization of leads for multifactorial disease systemic sclerosis
| Project/Area Number |
17H03999
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | Kumamoto University |
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Principal Investigator |
Otsuka Masami 熊本大学, 大学院生命科学研究部(薬), 客員教授 (40126008)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | 全身性強皮症 |
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| Outline of Final Research Achievements |
Aiming at remedy of multifactorial disease systemic sclerosis, a compound HPH-15 discovered by phenotype screening using cell morphological changes, a prodrug of IP6 that has various physiological activities, and a carnosine derivative that eliminate cytotoxic aldehyde HNE were investigated.
A total of 20 HPH-15 derivatives were synthesized, and 10 of them showed stronger activity than HPH-15 in suppressing collagen production in human skin cells. We also identified the target protein of HPH-15. On the other hand, we demonstrated that the IP6 prodrug Pro-IP6 is cell-permeable and converted into IP6 in the cells. A carnosine derivative CNN showed the HNE capturing activity superior to that of carnosine.
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| Academic Significance and Societal Importance of the Research Achievements |
全身性強皮症は皮膚や組織にコラーゲンが蓄積して硬化、線維化する自己免疫疾患である。明確な原因が不明で、対症療法のみで根治薬がなく、難病に指定されている。しばしば間質性肺炎、腎クリーゼなどの内臓線維化による重篤な疾患を併発し、死に至る場合もある。本研究ではさきに見出していた化合物HPH-15より優れた活性を示す誘導体を合成し、その標的蛋白質を同定した。さらにIP6のプロドラッグと細胞毒性アルデヒドHNEを消去するCNNを開発した。本研究では多因子疾患全身性強皮症に対して複数の標的に作用する化合物を見出したことから、全身性強皮症治療薬開発へと結びつくものと期待される。
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Report
(2 results)
Research Products
(18 results)
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[Journal Article] Design, synthesis and biological evaluation of novel 1,3,4-Thiadiazole derivatives as potential antitumor agents against chronic myelogenous leukemia. Striking effect of nitrothiazole moiety.2018
Author(s)
Altintop, M.D., Ciftci, H.I., Radwan, M.O., Sever, B., Kaplancikli, Z.A., Ali, T.F.S., Koga, R., Fujita, M., Otsuka, M., and Ozdemir, A.
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Journal Title
Molecules
Volume: 23
Issue: 1
Pages: 59-59
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The First Pentacyclic Triterpenoid Gypsogenin Derivative Exhibiting Anti-ABL1 Kinase and Anti-chronic Myelogenous Leukemia Activities2018
Author(s)
Ciftci, H.I., Ozturk, S.E., Ali, T.F.S., Radwan, M.O., Tateishi, H., Koga, R., Ocak, Z., Can, M., Otsuka, M., and Fujita, M.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 41
Issue: 4
Pages: 570-574
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Development of a novel method for HIV eradication: “lock-in and apoptosis”2018
Author(s)
Tateishi, Hiroshi; Ciftci, Halil Ibrahim; Koga, Ryoko; Monde, Kazuaki; Anraku, Kensaku; Koiwai, Kotaro; Yumoto, Fumiaki; Senda, Toshiya; Otsuka, Masami; Fujita, Mikako
Organizer
Frontiers in Retrovirology Conference 2018
Related Report
Int'l Joint Research
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