Building and establishing platform technologies for Structure Based Drug Design targeting AdipoR
| Project/Area Number |
26293216
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Iwabu Miki 東京大学, 医学部附属病院, 特任講師 (70392529)
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| Co-Investigator(Renkei-kenkyūsha) |
IWABU Masato 東京大学, 医学部附属病院, 特任准教授 (30557236)
YAMAUCHI Toshimasa 東京大学, 医学部附属病院, 准教授 (40372370)
KADOWAKI Takashi 東京大学, 医学部附属病院, 教授 (30185889)
TOKOYAMA Shigeyuki 独立行政法人理化学研究所, 横山構造生物学研究室, 上席研究員 (00159229)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
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| Keywords | 糖尿病 / 薬理学 / トランスレーショナルリサーチ |
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| Outline of Final Research Achievements |
We have so far clarified that adiponectin, an adipocyte-secreted physiologically active substance, is decreased with the onset of obesity and that lifestyle-related diseases are primarily accounted for by the systemically decreased action of adiponectin/adiponectin receptors (AdipoRs). We were the first in the world to succeed in identifying small-molecule compounds that serve as seed compounds for candidate AdipoR-activating drugs. In the process, we have also reported the crystal structures of AdipoRs, which allowed the seed compounds to be structurally developed, examined for their anti-diabetic properties at the cellular and organism levels, and optimized as candidate compounds for clinical development, with their activity, specificity and safety highly enhanced over those of existing small-molecule AdipoR-activating compounds. It is hoped that these milestones will lead to the development of novel anti-diabetic drugs.
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Report
(4 results)
Research Products
(42 results)
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[Journal Article] Crystal structures of the human adiponectin receptors.2015
Author(s)
Tanabe H, Fujii Y, Okada-Iwabu M, Iwabu M, Nakamura Y, Hosaka T, Motoyama K. Ikeda M, Wakiyama M, Terada T, Ohsawa N, Hato M, …, Kimura-Someya T, Shirouzu M, Yamauchi T, Kadowaki T, Yokoyama S
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Journal Title
Nature
Volume: 520
Pages: 312-316
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] A novel peroxisome proliferator-activated receptor (PPAR) α agonist and PPAR γ antagonist, Z-551, ameliorates high-fat diet-induced obesity and metabolic disorders in mice.2015
Author(s)
Shiomi Y, Yamauchi T, Iwabu M, Okada-Iwabu M, Nakayama R, Orikawa Y, Yoshioka Y, Tanaka K, Ueki K, Kadowaki T
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Journal Title
J. Biol. Chem.
Volume: 290
Pages: 14567-14581
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Expression, purification, crystallization, and preliminary X-ray crystallographic studies of the human adiponectin receptors, AdipoRl and AdipoR22015
Author(s)
Tanabe H,..., Iwata S, Okada-Iwabu M, Iwabu M,..., Yamauchi T, Kadowaki T, and Yokoyama S
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Journal Title
J Struct Funct Genomics.
Volume: 16
Pages: 11-23
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Crystal structures of the human adiponectin receptors2015
Author(s)
MIKI OKADA-IWABU, TOSHIMASA YAMAUCHI, MASATO IWABU,TAKASHI KADOWAKI
Organizer
2016 Keystone Symposia Conference T2: Diabetes: New Insights into Molecular Mechanisms and Therapeutic Strategies
Place of Presentation
Westin Miyako Kyoto（京都府京都市）
Year and Date
2015-10-13
Related Report
Int'l Joint Research
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