2013 Fiscal Year Final Research Report
A novel mode of action of DNA alkylating anticancer agents
| Project/Area Number |
23510281
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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 | University of Shizuoka |
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Principal Investigator |
ASAI AKIRA 静岡県立大学, 薬学研究科(研究院), 教授 (60381737)
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| Project Period (FY) |
2011 – 2013
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| Keywords | がん / 抗がん剤 / DNAアルキル化剤 / 転写制御因子 / STAT3 / SH2 |
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| Research Abstract |
Bendamustine (Benda) is an anti-lymphoma drug, which was recently approved in Japan. Although DNA has been believed to be primary target of this agent, the details of mechanism of action still remain unclear. We herein, for the first time, report STAT3 inhibition by Benda. The STAT3-SH2 antagonistic activity was shown by Benda but not by the inactive metabolites in the biochemical assay using recombinant human STAT3 protein. Furthermore, Benda suppressed both DNA-binding and transcriptional activity of STAT3 in the human breast cancer cell line MDA-MB-463. The competitive pull-down assay using the Benda analogs revealed that this agent tightly bound to cellular STAT3. Therefore, those results suggest that the previously reported anti-cancer and immunomodulation effects by this agent might be associated with its inhibitory effect on STAT3.
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[Journal Article] Effect of the STAT3 inhibitor STX-0119 on the proliferation of a temozolomide-resistant glioblastoma cell line2014
Author(s)
Ashizawa T, Akiyama Y, Miyata H, Iizuka A, Komiyama M, Kume A, Omiya M, Sugino T, Asai A, Hayashi N, Mitsuya K, Nakasu Y, Yamaguchi K
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Journal Title
Int J Oncol.
Volume: 411-8
DOI
Peer Reviewed
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[Journal Article] Synthesis, structure.activity relationships and stereochemical investigations of new tricyclic pyridazinone derivatives as potential STAT3 inhibitors2013
Author(s)
Masciocchi D, Gelain A, Porta F, Meneghetti F, Pedretti A, Celentano G, Barlocco D, Legnani L, Toma L, Kwon B, Asai A, Villa S
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Journal Title
Med Chem Commun.
Volume: 4
Pages: 1181-1188
Peer Reviewed
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[Journal Article] Effect of the STAT3 inhibitor STX-0119 on the proliferation of cancer stem-like cells derived from recurrent glioblastoma2013
Author(s)
Ashizawa T, Miyata H, Iizuka A, Komiyama M, Oshita C, Kume A, Nogami M, Yagoto M, Ito I, Oishi T, Watanabe R, Mitsuya K, Matsuno K, Furuya T, Okawara T, Otsuka M, Ogo N, Asai A, Nakasu Y, Yamaguchi K, Akiyama Y
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Journal Title
Int J Oncol.
Volume: 43
Pages: 219-217
Peer Reviewed
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[Journal Article] Biological and computational evaluation of an oxadiazole derivative (MD77) as a new lead for direct STAT3 inhibitors2012
Author(s)
Masciocchi D, Villa S, Meneghetti F, Pedretti A, Barlocco D, Legnani L, Toma L, Kwon B, Nakano S, Asai A, Gelain A
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Journal Title
Med Chem Commun.
Volume: 3
Pages: 592-599
Peer Reviewed
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[Presentation] MERGED STRUCTURES AS NEW STAT3 INHIBITORS: THE "CHIMERA" COMPOUNDS2012
Author(s)
Arianna Gelain, Daniela Masciocchi, Stefania Villa, Fiorella Meneghetti, Alessandro Pedretti, Daniela Barlocco, Laura Legnani, Lucio Toma, Byoung-Mog Kwon, Shintaro Nakano, Akira Asai
Organizer
22nd International Symposium on Medicinal Chemistry
Place of Presentation
Berlin
Year and Date
2012-09-05
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[Presentation] New STAT3 inhibitors2012
Author(s)
Arianna Gelain, Daniela Masciocchi, Stefania Villa, Fiorella Meneghetti, Alessandro1 Pedretti, Daniela Barlocco, Laura Legnani, Lucio Toma, Byoung-Mog Kwon, Shintaro Nakano, Akira Asai
Organizer
identification of a lead 21st National Meeting on Medicinal Chemistry
Place of Presentation
Palermo
Year and Date
2012-07-18
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