Discovery of ligands that modulate the pocket structure of vitamin D receptor
| Project/Area Number |
23590135
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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 |
Drug development chemistry
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| Research Institution | Showa Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | ビタミンＤ / ビタミンＤ受容体 / アゴニスト / アンタゴニスト / パーシャルアゴニスト / 結晶構造 / 核内受容体 / ポケット構造 / 受容体 / 遺伝子転写 / アナログ / ビタミンD / ビタミンD受容体 |
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| Research Abstract |
To develop vitamin D receptor ligands which separate the various biological activities of 1a,25-dihydroxyvitamin D3, we focused on the structure of ligand-binding pocket of the receptor, especially the variable part of the pocket. As a result, we discovered vitamin D analogues with a branched side chain that induce structural rearrangement of the amino acid residues lining the ligand-binding pocket. These analogs showed agonistic, partial agonistic or antagonistic activities. By X-ray analysis, we found one of partial agonists exists in two conformations, namely agonist and antagonist conformations, in a single crystal.
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Report
(4 results)
Research Products
(23 results)
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[Presentation] Vitamin D Analogs with Simple Side Chain Structure : Agonists, Partial Agonists, and Antagonists for the Vitamin D Receptor2011
Author(s)
Keiko Yamamoto, Yuta Sakamaki, Yuka Inaba, Nobuko Yoshimoto, Toshimasa Itoh, Makoto Nakabayashi, Teikichi Ikura, Nobutoshi Ito
Organizer
8th AFMC International Medicinal Chemistry Symposium. Frontier of Medicinal Science
Place of Presentation
Tokyo, Japan
Year and Date
2011-12-01
Related Report
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