Screening of NF-kappa B inhibitors having new core structure and application to aggressive cancer treatment
| Project/Area Number |
26350975
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Chemical biology
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| Research Institution | Aichi Medical University |
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Principal Investigator |
Umezawa Kazuo 愛知医科大学, 医学部, 教授 (70114402)
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| Co-Investigator(Kenkyū-buntansha) |
須貝 威 慶應義塾大学, 薬学部(芝共立), 教授 (60171120)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | NF-kappa B / 分子デザイン / 天然物 / がん / 転移 / 炎症 / DHMEQ / desmal / 阻害剤 / スクリーニング / 分子標的 / SEMBL / 放線菌 / (-)-DHMEQ / Exo-ene EQ |
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| Outline of Final Research Achievements |
Metastasis inhibitors are expected as new chemotherapeutic agents with little side effects. We previously discovered DHMEQ as an NF-kappa B inhibitor. It shows various anti-inflammatory and anticancer activities in animal experiments, but it contains epoxide moiety that causes instability. In the present research, we designed and synthesized an epoxide-free DHMEQ analog called SEMBL. SEMBL inhibited NF-kappa B as DHMEQ. It also inhibited cellular migration and invasion in ovarian carcinoma cells more strongly than DHMEQ. Moreover, it was shown to be more stable than DHMEQ in aqueous solution (published in 2017). In one hand, we previously discovered a novel plant-derived flavonoid desmal. In the present research, dismal was found to inhibit NF-kappa B. It also inhibited cellular migration and invasion in ovarian carcinoma cells (published in 2016). These inhibitors will be useful for the mechanistic study of metastasis and for the development of new chemotherapeutic agents.
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Report
(4 results)
Research Products
(84 results)
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[Journal Article] Rational design, synthesis and in vitro evaluation of novelexo-methylene butyrolactone salicyloylamide as NF-κB inhibitor2017
Author(s)
K. Sidthipong, J. Ma, W. L. Yu, Y. F. Wang, S. Kobayashi, S. Kishino , N. Koide, T. Yokochi, K. Kato, S. Okada and K. Umezawa
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Journal Title
Bioorg. Med. Chem. Lett. 27: 562-566, 2017.
Volume: 27
Pages: 562-566
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] A novel anti-inflammatory agent, DTCM-glutarimide, ameliorates murine models of inflammatory bowel disease.2016
Author(s)
N. Ichikawa, K. Yamashita, T. Funakoshi, S. Ichihara, M. Fukai, M. Ogura, N. Kobayashi, M. Zaitsu, T. Yoshida, S. Shibasaki, Y. Koshizuka, Y. Tsunetoshi, M. Sato, T. Einama, M. Ozaki, K. Umezawa, T. Suzuki and S. Todo
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Journal Title
Inflammation Research
Volume: 65
Issue: 3
Pages: 245-260
DOI
Related Report
Peer Reviewed
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[Journal Article] A nuclear factor-κB inhibitor, dehydroxymethylepoxyquinomicin, ameliorates GVHD in allogeneic bone marrow transplantation.2015
Author(s)
S. Yamanouchi, Y. Adachi, T. Shimo, K. Umezawa, M. Okigaki, S. Tsuji, M Li, J. Takaya, T. Kuge, S. Ikehara, K. Kaneko
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Journal Title
Immunobiology
Volume: 220
Issue: 9
Pages: 1059-1066
DOI
Related Report
Peer Reviewed
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[Journal Article] Dehydroxymethylepoxyquinomicin, a novel nuclear factor–κB inhibitor, reduces chemokines and adhesion molecule expression induced by IL-1β in human corneal fibroblasts2015
Author(s)
S. Inokawa, T. Watanabe, H. Keino, Y. Sato, A. Hirakata, A. A. Okada, K. Fukuda, A. Fukushima, K. Umezawa
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Journal Title
Graefes Arch. Clin. Exp. Ophthalmol.
Volume: VOL. 253
Pages: 557-563
Related Report
Peer Reviewed
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[Journal Article] Immunosuppression through constitutively activated NF-κB signaling in human ovarian cancer and its reversal by a NF-κB inhibitor2014
Author(s)
H. Nishio, T. Yaguchi, J. Sugiyama, H. Sumimoto, K. Umezawa, T. Iwata, N. Susumu, T.Fujii, N. Kawamura, A. Kobayashi, J-H Park, D. Aoki, Y. Kawakami
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Journal Title
British Journal of Cancer
Volume: VOL. 110
Pages: 2965-2974
Related Report
Peer Reviewed
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[Journal Article] Anoikis induction and inhibition of peritoneal metastasis of pancreatic cancer cells by a nuclear factor-kappa B inhibitor, (-)-DHMEQ2014
Author(s)
M. Sato, K. Nakanishi, S. Haga, M. Fujiyoshi, M. Baba, K. Mino, Yimin, H. Niwa, H. Yokoo, K. Umezawa, Y. Ohmiya, T. Kamiyama, S. Todo, A. Taketomi, M. Ozaki
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Journal Title
Oncology Research
Volume: VOL. 21
Pages: 333-343
Related Report
Peer Reviewed / Open Access
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