Highlighted paper selected by editor-in-chief: Pharmacology and in vitro profiling of a novel peroxisome proliferator-activated receptor γ ligand, Cerco-A
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- Wakabayashi Kenji
- Graduate School of Life and Environmental Sciences, University of Tsukuba Kasai R&D Center, Daiichi Sankyo Co., Ltd. Shinagawa R&D Center, Daiichi Sankyo Co., Ltd. Bioassesssment Group I, Research Department III, Daiichi Sankyo RD Associe Co., Ltd.
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- Hayashi Shinko
- Kasai R&D Center, Daiichi Sankyo Co., Ltd.
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- Matsui Yumi
- Shinagawa R&D Center, Daiichi Sankyo Co., Ltd.
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- Matsumoto Takuo
- Kasai R&D Center, Daiichi Sankyo Co., Ltd.
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- Furukawa Akihiro
- Shinagawa R&D Center, Daiichi Sankyo Co., Ltd.
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- Kuroha Masanori
- Shinagawa R&D Center, Daiichi Sankyo Co., Ltd.
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- Tanaka Naomi
- Shinagawa R&D Center, Daiichi Sankyo Co., Ltd.
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- Inaba Tomoko
- Shinagawa R&D Center, Daiichi Sankyo Co., Ltd.
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- Kanda Shoichi
- Shinagawa R&D Center, Daiichi Sankyo Co., Ltd.
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- Tanaka Jun
- Shinagawa R&D Center, Daiichi Sankyo Co., Ltd.
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- Okuyama Ryo
- Shinagawa R&D Center, Daiichi Sankyo Co., Ltd.
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- Wakimoto Satoko
- Shinagawa R&D Center, Daiichi Sankyo Co., Ltd.
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- Ogata Tsuneaki
- Shinagawa R&D Center, Daiichi Sankyo Co., Ltd.
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- Araki Kazushi
- Shinagawa R&D Center, Daiichi Sankyo Co., Ltd.
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- Ohsumi Jun
- Shinagawa R&D Center, Daiichi Sankyo Co., Ltd.
書誌事項
- タイトル別名
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- Pharmacology and in Vitro Profiling of a Novel Peroxisome Proliferator-Activated Receptor .GAMMA. Ligand, Cerco-A
- Highlighted paper selected by editor in chief Pharmacology and in vitro profiling of a novel peroxisome proliferator activated receptor g ligand Cerco A
この論文をさがす
抄録
Peroxisome proliferator-activated receptor γ (PPARγ; NR1C3) is known as a key regulator of adipocytogenesis and the molecular target of thiazolidinediones (TZDs), also known as antidiabetic agents. Despite the clinical benefits of TZDs, their use is often associated with adverse effects including peripheral edema, congestive heart failure, and weight gain. Here we report the identification and characterization of a non-thiazolidinedione PPARγ partial agonist, Cerco-A, which is a derivative of the natural product, (−)-cercosporamide. Cerco-A was found to be a binder of the PPARγ ligand-binding domain in a ligand competitive binding assay and showed a unique cofactor recruitment profile compared to rosiglitazone. A crystal structure analysis revealed that Cerco-A binds to PPARγ without direct hydrogen bonding to helix12. In PPARγ transcriptional activation assay and an adipocyte differentiation assay, Cerco-A was a potent partial agonist of PPARγ. After a 14-day oral administration, once per day of Cerco-A in Zucker diabetic fatty (ZDF) rats, an apparent decrease of plasma glucose and triglyceride was observed, as with pioglitazone. To evaluate drug safety, Cerco-A was administered for 13 days orally in non-diabetic Zucker fatty (ZF) rats. Each of the hemodilution parameters (hematocrit, red blood cells number, and hemoglobin), which are considered as undesirable effects of TZDs, was improved significantly compared to pioglitazone. While Cerco-A showed body weight gain, as with pioglitazone, Cerco-A had significantly lower effects on heart and white adipose tissues weight gain. The results suggest that Cerco-A offers beneficial effects on glycemic control with attenuated undesirable side effects.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 34 (7), 1094-1104, 2011
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679609402752
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- NII論文ID
- 130000738102
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 11132774
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可