Development of novel anti-breast cancer drugs that can induce degradation of estrogen receptor
Project/Area Number |
26860085
|
Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Drug development chemistry
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Research Institution | National Institute of Health Sciences |
Principal Investigator |
Shoda Takuji 国立医薬品食品衛生研究所, 有機化学部, 室長 (60435708)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 乳がん治療薬 / 選択的エストロゲン受容体分解薬 / タモキシフェン / 選択的エストロゲン受容体分解誘導剤 |
Outline of Final Research Achievements |
Estrogen receptors (ERs) play a major role in the growth of human breast cancer cells. An antagonist that acts as not only an inhibitor of ligand binding but also an inducer of the down-regulation of ER would be useful for the treatment for ER-positive breast cancer. We designed and synthesized various tamoxifen derivatives that have various lengths and terminal groups of the long alkyl side chain. During the course of our investigation, C10F having a 10-fluorodecyl group on the amine moiety of 4-OHT was shown to be the most potent compound among the tamoxifen derivatives. Moreover, computational docking analysis suggested that the long alkyl chain interacted with the hydrophobic region on the surface of the ER, which is a binding site of helix 12 and coactivator. These results provide useful information to develop promising candidates as SERDs.
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Report
(4 results)
Research Products
(36 results)
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[Journal Article] Design and synthesis of novel selective estrogen receptor degradation inducers based on diphenylheptane skeleton2017
Author(s)
T. Misawa, T. Fujisato, Y. Kanda, N. Ohoka, T. Shoda, M. Yorioka, M. Makishima, Y. Sekino, M. Naito, Y. Demizu, Masaaki Kurihara
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Journal Title
MedChemComm
Volume: 8
Issue: 1
Pages: 239-246
DOI
Related Report
Peer Reviewed
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[Journal Article] Development of BCR-ABL degradation inducers via the conjugation of an imatinib derivative and a cIAP1 ligand.2016
Author(s)
Demizu, Y., Shibata, N., Hattori, T., Ohoka, N., Motoi, H., Misawa, T., Shoda, T., Naito, M. & Kurihara, M.
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Journal Title
Bioorg Med Chem Lett
Volume: 26
Issue: 20
Pages: 4865-4869
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Development of cell-penetrating R7 fragment-conjugated helical peptides as inhibitors of estrogen receptor-mediated transcription.2014
Author(s)
2.Nagakubo, T., Demizu, Y., Kanda, Y., Misawa, T., Shoda, T., Okuhira, K., Sekino., Y., Naito, M. and Kurihara, M
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Journal Title
Bioconjug Chem.
Volume: 25
Issue: 11
Pages: 1921-24
DOI
Related Report
Peer Reviewed
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[Journal Article] Illuminating HIV-1 gp120–Ligand Recognition through Computationally-Driven Optimization of Antibody-Recruiting Molecules2014
Author(s)
5.Christopher G. Parker, Markus K. Dahlgren, Don T. Li, Eugene F. Douglass, Takuji Shoda, Navneet Jawanda, Krasimir A. Spasov, Robert A. Domaoal, Richard Sutton, Karen S. Anderson, William L. Jorgensen, David A. Spiegel
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Journal Title
Chemical Science
Volume: 5
Issue: 6
Pages: 2311-2317
DOI
Related Report
Peer Reviewed
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[Journal Article] Design and synthesis of tamoxifen derivatives as a selective estrogen receptor down-regulator.2014
Author(s)
Shoda, T., Okuhira, K., Kato, M., Demizu, Y., Inoue, H., Naito, M., and Kurihara, M.
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Journal Title
Bioorg Med Chem Lett
Volume: 24
Issue: 1
Pages: 87-89
DOI
Related Report
Peer Reviewed
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