Practical medicinal chemistry on the basis of protein chemistry, computational science and synthetic technologies for a variety of heterocycles
Project/Area Number |
23390025
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Drug development chemistry
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Research Institution | Kyoto University |
Principal Investigator |
FUJII Nobutaka 京都大学, 薬学研究科(研究院), 教授 (60109014)
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Co-Investigator(Kenkyū-buntansha) |
KITAURA Kazuo 神戸大学, 大学院システム情報学研究科, 教授 (30132723)
OHNO Hiroaki 京都大学, 大学院薬学研究科, 教授 (30322192)
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Project Period (FY) |
2011-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2012: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2011: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
|
Keywords | CXCR4 / CXCR7 / ケモカイン / CK2 / キナーゼ / KSP / キネシン / 複素環 / CXCR4ケモカイン受容体 / CXCR7ケモカイン受容体 / ホモロジーモデル / プロテインキナーゼCK2 / スフィンゴシンキナーゼ / jaspine B / FC131 / キネシンモータータンパク / 分子設計 / ドラッグライク / ケモカイン受容体 / 複素環骨格構築反応 |
Outline of Final Research Achievements |
The structural requirements and binding modes of cyclic pentapeptide CXCR4 antagonists were revealed via a structure-activity relationship study using a series of peptidomimetics as well as molecular modeling studies. Novel CXCR7 ligands with cyclic peptide and heterocyclic scaffolds were also identified via two lead-discovery approaches. Several facile synthetic processes for unique nitrogen heterocycles were established using transition-metal catalyzed multi-component reactions and applied to the synthesis of a number of potent CK2 kinase inhibitors and KSP inhibitors with favorable physicochemical properties.
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Report
(4 results)
Research Products
(109 results)
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[Journal Article] Structure-activity relationship study on senktide for development of novel potent neurokinin-3 receptor selective agonists.2015
Author(s)
Misu R, Yamamoto K, Yamada A, Noguchi T, Ohno H, Yamamura T, Okamura H, Matsuda F, Ohkura S, Oishi S, Fujii N.
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Journal Title
MedChemCommun
Volume: 6
Issue: 3
Pages: 469-476
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A radiogallium-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging2014
Author(s)
Sano K, Masuda R, Hisada H, Oishi S, Shimokawa K, Ono M, Fujii N, Saji H, Mukai T.
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Journal Title
Bioorg. Med. Chem. Lett.
Volume: 24
Issue: 5
Pages: 1386-1388
DOI
Related Report
Peer Reviewed
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[Journal Article] Development of novel neurokinin 3 receptor (NK3R) selective agonists with resistance to proteolytic degradation.2014
Author(s)
Misu R, Oishi S, Yamada A, Yamamura T, Matsuda F, Yamamoto K, Noguchi T, Ohno H, Okamura H, Ohkura S, Fujii N.
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Journal Title
J. Med. Chem.
Volume: 57
Issue: 20
Pages: 8646-8651
DOI
Related Report
Peer Reviewed
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[Journal Article] Structure-activity relationship study of phenylpyrazole derivatives as a novel class of anti-HIV agents2013
Author(s)
Mizuhara T, Kato T, Hirai A, Kurihara H, Shimada Y, Taniguchi M, Maeta M, Togami H, Shimura K, Matsuoka M, Okazaki S, Takeuchi T, Ohno H, Oishi S, Fujii N.
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Journal Title
Bioorg. Med. Chem. Lett.
Volume: 23
Issue: 16
Pages: 4557-4561
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Paradoxical downregulation of CXC chemokine receptor 4 induced by polyphemusin II-derived antagonists.2012
Author(s)
Masuda R, Oishi S, Tanahara N, Ohno H, Hirasawa A, Tsujimoto G, Yano Y, Matsuzaki K, Navenot J, Peiper S, Fujii N.
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Journal Title
Bioconjug. Chem.
Volume: 23
Issue: 6
Pages: 1259-1265
DOI
Related Report
Peer Reviewed
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[Journal Article] Design and synthesis of novel class of CK2 inhibitors : application of copper- and gold-catalysed cascade reactions for fused nitrogen heterocycles.2012
Author(s)
Suzuki Y, Oishi S, Takei Y, Yasue M, Misu R, Naoe S, Hou Z, Kure T, Nakanishi I, Ohno H, Hirasawa A, Tsujimoto G, Fujii N.
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Journal Title
Org. Biomol. Chem.
Volume: 10
Issue: 25
Pages: 4907-4915
DOI
Related Report
Peer Reviewed
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[Journal Article] Non-invasive longitudinal imaging of tumor progression using an 111Indium labeled CXCR4 peptide antagonist.2012
Author(s)
Buckle T, Van den Berg NS, Kuil J, Bunschoten A, Oldenburg J, Borowsky AD, Wesseling J, Masada R, Oishi S, Fujii N, Van Leeuwen FB.
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Journal Title
Am. J. Nucl. Med. Mol. Imaging,
Volume: 2
Pages: 99-109
Related Report
Peer Reviewed
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[Journal Article] Structure-based Design of Novel Potent CK2 Inhibitors with Phenyl-azole Scaffolds.2012
Author(s)
Z. Hou, I. Nakanishi, T. Kinoshita, Y. Takei, M. Yasue, R. Misu, Y. Suzuki, S. Nakamura, T. Kure, H. Ohno, K. Murata, K. Kitaura, A. Hirasawa, G. Tsujimoto, S. Oishi, N. Fujii.
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Journal Title
J. Med. Chem.
Volume: 55
Issue: 6
Pages: 2899-2903
DOI
Related Report
Peer Reviewed
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[Presentation] Identification of Novel CXCR7 Selective Ligands with Cyclic Pentapeptide Scaffold2014
Author(s)
Tomoko Kuroyanagi, Shinya Oishi, Tatsuhiko Kubo, Yuka Kobayashi, Ryosuke Misu, Hiroaki Ohno, Nicolas Montpas, Nikolaus Heveker, Yasushi Yoshikawa, Toshio Furuya, Nobutaka Fujii
Organizer
第51回ペプチド討論会
Place of Presentation
徳島大学 (徳島県徳島市)
Year and Date
2014-10-22 – 2014-10-24
Related Report
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[Presentation] Development of novel neurokinin-3 receptor selective agonists with resistance against proteolytic degradation2014
Author(s)
Ryosuke Misu, Shinya Oishi, Ai Yamada, Koki Yamamoto, Taro Noguchi, Hiroaki Ohno, Takashi Yamamura, Hiroaki Okamura, Fuko Matsuda, Satoshi Ohkura, Nobutaka Fujii
Organizer
第51回ペプチド討論会
Place of Presentation
徳島大学 (徳島県徳島市)
Year and Date
2014-10-22 – 2014-10-24
Related Report
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[Presentation] Synthetic Studies on Coibamide A2013
Author(s)
Ryota Nabika, Shinya Oishi, Hiroaki Ohno, Nobutaka Fujii
Organizer
The First Asian Conference for ''MONODUKURI'' Strategy by Synthetic Organic Chemistry
Place of Presentation
Southern Beach Hotel & Resort Okinawa(沖縄県糸満市)
Year and Date
2013-07-17 – 2013-07-19
Related Report
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[Presentation] INTERNALIZATION OF CXC CHEMOKINE RECEPTOR 4 (CXCR4) INDUCED BY POLYPHEMUSIN II-DERIVED ANTAGONIST PEPTIDES2011
Author(s)
Masuda R, Oishi S, Tanahara N, Ohno H, Hirasawa A, Tsujimoto G, Yano Y, Matsuzaki K, Nakase I, Futaki S, Fujii N.
Organizer
第48回ペプチド討論会
Place of Presentation
札幌コンベンションセンター(北海道)
Related Report
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