Development and its Application of Novel Drug Design based on the first-principles calculation
Project/Area Number |
25460157
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Drug development chemistry
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Research Institution | Rikkyo University |
Principal Investigator |
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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Keywords | in silico創薬 / 理論創薬 / 全電子計算 / フラグメント分子軌道法 / 核内受容体 / インフルエンザ / 合理的創薬 / 高精度全電子計算 / インフルエンザウイルス / デングウイルス / 生活習慣病 / 遊離脂肪酸 |
Outline of Final Research Achievements |
Novel Drug Design procedure combined the first-principles calculation using ab initio fragment molecular orbital (FMO) method with bioinfomatics were established. Correlated FMO calculations can evaluate correctly not only hydrophilic (electrostatic) but also hydrohobic (van der Waals dispersion) interactions between amino acid residues in target protein and drug candidates. New anti-influenza virus inhibitors were rationally developed by the interfragment interaction energy (IFIE) analysis based on the FMO scheme. And antidiabetic compounds without side effect as partial agonists for nuclear receptors such as vitamin D receptor (VDR), retinoid X receptor (RXR), and steroid X receptor (SXR) were also developed and synthetized. The functional domain in the target protein was explored by the sequence alignment analysis, and key residues between these candidates and target protein were determined by the FMO-IFIE analysis.
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Report
(4 results)
Research Products
(166 results)
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[Journal Article] A Novel Potent and Highly Specific Inhibitor against Influenza Viral N1-N9 Neuraminidases: Insight into Neuraminidase-inhibitor Interactions2016
Author(s)
Nongluk Sriwilaijaroen, Sadagopan Magesh, Akihiro Imamura, Hiromune Ando, Hideharu Ishida, Miho Sakai, Erika Ishitsubo, Takanori Hori, Setsuko Moriya, Takeshi Ishikawa, Kazuo Kuwata, Takato Odagiri, Masato Tashiro, Hiroaki Hiramatsu, Kenji Tsukamoto, Taeko Miyagi, Hiroaki Tokiwa, Makoto Kiso, and Yasuo Suzuki
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Journal Title
J.Med.Chem.
Volume: 59
Issue: 10
Pages: 4563-4577
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Synthesis, Biological Activities and X-ray Crystal Structural Analysis of 25-Hydroxy-25(or 26)-adamantyl-17-[20(22),23-diynyl]-21-norvitamin D Compounds2015
Author(s)
Yusuke Watarai, Michiyasu Ishizawa, Teikichi Ikura, Flavia C. M. Zacconi, Shigeyuki Uno, Nobutoshi Ito, Antonio Mourino, Hiroaki Tokiwa, Makoto Makishima, and Sachiko Yamada
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Journal Title
J.Med.Chem.
Volume: 58 (24)
Issue: 24
Pages: 9510-9521
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Synthetic Small Molecules Derived from Natural Vitamin K Homologues that Induce Selective Neuronal Differentiation of Neuronal Progenitor Cells2015
Author(s)
Yoshitomo Suhara,Yoshihisa Hirota, Norika Hanada, Shun Nishina, Sachiko Eguchi, Rie Sakane, Kimie Nakagawa, Akimori Wada, Kazuhiko Takahashi, Hiroaki Tokiwa, and Toshio Okano
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Journal Title
J.Med.Chem.
Volume: 58 (17)
Issue: 17
Pages: 7088-7092
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Amino acid substitutions contributing to α2,6-sialic acid linkage binding specificity of human parainfluenza virus type 3 hemagglutinin-neuraminidase.2015
Author(s)
Fukushima K, Takahashi T, Ueyama H, Takaguchi M, Ito S, Oishi K, Minami A, Ishitsubo E, Tokiwa H, Takimoto T, Suzuki T.
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Journal Title
FEBS Lett.
Volume: 589
Issue: 11
Pages: 1278-1282
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Combination of Triple Bond and Adamantane Ring on the Vitamin D Side Chain Produced Partial Agonists for Vitamin D Receptor2014
Author(s)
Takeru Kudo, Michiyasu, Ishizawa, Kazuki Maekawa, Makoto Nakabayashi, Yusuke Watarai, Hikaru Uchida, Hiroaki Tokiwa, Teikichi Ikura, Nobutoshi Ito, Makoto Makishima, Sachiko Yamada,
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Journal Title
J. Med. Chem.
Volume: 57(10)
Issue: 10
Pages: 4073-4087
DOI
Related Report
Peer Reviewed
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[Journal Article] Vitamin D Receptor Mutants R270L and W282R Bound to 1,25-Dihydroxyvitamin D3 and Synthetic Ligands2013
Author(s)
Makoto Nakabayashi, Yoshito Tsukahara, Yukiko Iwasaki-Miyamoto, Mika Mihori-Shimazaki, Sachiko Yamada, Satomi Inaba, Masayuki Oda, Masato Shimizu, Makoto Makishima, Hiroaki Tokiwa, Teikichi Ikura, Nobutoshi Ito
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Journal Title
Journal of Medicinal Chemistry
Volume: 56(17)
Issue: 17
Pages: 6745-6760
DOI
Related Report
Peer Reviewed
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[Journal Article] Catalytic preference of Salmonella typhimurium LT2 sialidase for N-acetylneuraminic acid residues over N-glycolylneuraminic acid residues2013
Author(s)
Akira Minami, Sayaka Ishibashi, Kiyoshi Ikeda, Erika Ishitsubo, Takanori Hori, Hiroaki Tokiwa, Risa Taguchi, Daisuke Ieno, Tadamune Otsubo, Yukino Matsuda, Saki Sai, Mari Inada and Takashi Suzuki
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Journal Title
FEBS Open Bio
Volume: 3
Issue: 1
Pages: 231-236
DOI
Related Report
Peer Reviewed
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[Journal Article] Generation of 3-Borylbenzynes, Their Regioselective Diels-Alder Reactions, and Theoretical Analysis2013
Author(s)
Takashi Ikawa, Akira Takagi, Yurio Kurita, Kozumo Saito, Kenji Azechi, Masahiro Egi, Yuji Itoh, Hiroaki Tkiwa, Yasuyuki Kita, and Shuji Akai
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Journal Title
Tetrahedron
Volume: 69
Issue: 21
Pages: 4338-4352
DOI
Related Report
Peer Reviewed
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[Presentation] Development of PyMOL plug-in, PaicsPy, to evaluate protein-ligand interaction by FMO method2015
Author(s)
Shogo Nakano, Takaki Tokiwa, Hiroaki Tateno, Naoki Kishimoto, Sohei Ito, Hiroaki Tokiwa and Jun Hirabayashi
Organizer
20th Shizuoka Forum on Health and longevity, (Shizuoka)
Place of Presentation
Convention & Arts Center "GRANSHIP", Shizuoka, Japan
Year and Date
2015-10-30
Related Report
Int'l Joint Research
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[Presentation] Theoretical study of anti-dengue virus inhibitors using the first-principles calculation and MD simulaton2015
Author(s)
Ayumi Sando, Tomoko Abe, Seiji Okazaki, Kazuya Hidari, Tadamune Ootsubo, Fumiteru. Teraoka, Kiyoshi Ikeda, Takashi Suzuki, Kouichi Morita, and Hiroaki Tokiwa
Organizer
23rd International Symposium on Glycoconjugates (GLYCO23)
Place of Presentation
LE MERIDIEN LAV, Split, Croatia
Year and Date
2015-09-15
Related Report
Int'l Joint Research
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[Presentation] Theoretical Interaction Analysis of Free Fatty Acid Receptor, GPR40 and GPR120 with omega-3 and omega-6 FFAs based on FMO Methods2015
Author(s)
Yuka Nakano, Erika Ishitsubo, Keisuke Hayamizu, L. Han, Tomoko Tsuji, Yasuo Watanabe, Shizuo Yamada, and Hiroaki Tokiwa
Organizer
12th Asian Congress of Nutrition (ACN2015)
Place of Presentation
Pacifico Yokohama, Yokohama, Japan
Year and Date
2015-05-14
Related Report
Int'l Joint Research
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[Presentation] Development of Novel Multi-target Inhibitor for HA & NA of Influenza Virus2014
Author(s)
Ishitsubo, E.; Hosozawa, T.; Igarashi, M.; Kirshner, K.N.; Sriwilaijaroen, N.; Yokoe, Hi.; Tsubuki, M.; Suzuki, Y.; Tokiwa, H
Organizer
Joint Meeting of the Society for Glycobiology (SFG) and the Japanse Society of Carbonhydrates Research (JSCR)
Place of Presentation
Sheraton Waikiki Hotel(Honolulu, Hawaii, USA)
Year and Date
2014-11-17
Related Report
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[Presentation] Development of Novel Multi-target Inhibitor for HA & NA of Influenza Virus2014
Author(s)
Ishitsubo, E.; Hosozawa, T.; Igarashi, M.; Kirshner, K.N.; Sriwilaijaroen, N.; Yokoe, H.; Tsubuki, M.; Suzuki, Y.; Tokiwa, H
Organizer
2nd International Conference on Pharma and Food
Place of Presentation
Nihontaira Hotel (Shizuoka, Japan)
Year and Date
2014-11-05
Related Report
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[Presentation] Rational design and development of a novel potent and highly specific inhibitor against influenza viral and human neuraminidases2013
Author(s)
Erika Ishitsubo, Takanori Hori, Miho Sakai, Nongluk Sriwilaijaroen, Sadagopan Magesh, Hiromune Ando, Shuji Ishida, Makoto Kiso,Taeko Miyagi, Yasuo Suzuki, Hiroaki Tokiwa
Organizer
International Conference of 5th Asain Communications of Glycobiology and Glycotechnology 2013
Place of Presentation
Khon Koen, Thailand
Related Report
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[Patent(Industrial Property Rights)] 米国特許2013
Inventor(s)
山田幸子、槇島誠、常盤広明他
Industrial Property Rights Holder
山田幸子、槇島誠、常盤広明他
Industrial Property Rights Type
特許
Filing Date
2013-08-30
Acquisition Date
2015-04-28
Related Report
Overseas
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