インスリン抵抗性改善薬ピオグリタゾンの創製
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概要
- 論文の詳細を見る
Insulin resistance is a characteristic feature of type II diabetes as well as obesity. This insulin resistant state at the peripheral tissue level causes impaired glucose utilization, leading to hyperglycemia. Studies of antidiabetic agents by Takeda originated more than three decades ago when KK mice were introduced, followed by the development of a highly insulin-resistant animal model, KKAy mice. The first 2,4-thiazolidinedione derivative AL-321, which exhibited hypoglycemic effects in KKAy mice, was discovered by modification of the hypolipidemic agent AL-294 as a lead compound. Extensive structure-activity relationship studies on the analogues of AL-321 led to the selection of ciglitazone (ADD-3878) as a candidate for clinical evaluation. Ciglitazone, a prototypical compound in the series, was shown to normalize hyperglycemia, hyperinsulinemia, and hypertriglyceridemia in various insulin-resistant animal models without altering normoglycemia in nondiabetic animal models. However, it appeared that a more potent compound was needed for further clinical evaluation of this class of compound. Further study of this series of compounds led to the finding of pioglitazone (AD-4833) as a promising clinical candidate. Pioglitazone clearly ameliorates the abnormal glucose and lipid metabolism in diabetic patients and was marketed in the USA in August 1999 for the treatment of type II diabetes. Pioglitazone is now marketed in more than 40 countries world wide. Historical aspects of our studies on pioglitazone and its biological activities are described.
- 社団法人 日本薬学会の論文
- 2002-11-01
著者
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池田 衡
丸石製薬株式会社中央研究所
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目黒 寛司
浜理薬品工業株式会社
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藤田 剛
防衛大学校 電気情報学群 電気電子工学科
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藤田 剛
大阪産業振興機構tlo事業部
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藤田 剛
オリエンタル酵母工業
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左右田 隆
武田薬品工業株式会社医薬研究本部
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川松 豊
干寿製薬株式会社経営戦略室
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左右田 隆
武田薬品工業(株)創薬第二研究所
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藤田 剛
浜松医科大学第二外科
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左右田 隆
武田薬品工業(株)創薬研究所IV
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