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METHOD FOR SCREENING OF THERAPEUTIC AGENT FOR HYPERLIPEMIA

外国特許コード F110003178
整理番号 A261-11WO
掲載日 2011年6月22日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2010JP070959
国際公開番号 WO 2011065389
国際出願日 平成22年11月25日(2010.11.25)
国際公開日 平成23年6月3日(2011.6.3)
優先権データ
  • 特願2009-269593 (2009.11.27) JP
発明の名称 (英語) METHOD FOR SCREENING OF THERAPEUTIC AGENT FOR HYPERLIPEMIA
発明の概要(英語) Disclosed are: a more highly safe treatment method for hyperlipemia; and a therapeutic agent for hyperlipemia. Specifically disclosed are: a novel method for screening for a therapeutic agent for hyperlipemia, more specifically a method for screening for a substance that can inhibit the production or function of ganglioside, particularly GM3, or inhibit the activity or expression of a GM3 synthase to decrease a blood lipid level; a pharmaceutical composition which can inhibit the production of ganglioside, particularly GM3, or the like specifically and is therefore effective for the treatment of hyperlipemia; and others.
従来技術、競合技術の概要(英語) BACKGROUND ART
Myocardial infarction, cerebral infarction related cardiovascular disease such as arteriosclerosis has been increasing every year, one of the main causes of death in adults is 1. Although a variety of causes of arteriosclerosis but, hyperlipidemia (hypercholesterolemia, hypertriglyceridemia and the like) is one of the most important causes being 1. The treatment of hypercholesterolemia, HMG-CoA reductase inhibitor (in particular the statin drug), agent such as anion exchange resin is used in the formulation. However, these agents are in addition to the biosynthesis of cholesterol ubiquinone Dolby recall, biomolecules such as heme A maintenance of functions of the components needed for also inhibit biosynthesis, due to this concern about side effects.
In recent years, a variety of metabolic diseases induced by obesity (insulin resistance, 2 diabetes mellitus, hyperlipidemia, arteriosclerosis, fatty liver and the like) sphingolipids in the importance of glycolipids (glycosphingolipid: GSL) has been revealed. As a basic skeleton of the ceramide GSL various sugar chain is added in the group of molecules, or of all the cells in the blood are present in the cell membrane. As the starting point is the body GSL biosynthesis by an enzymatic reaction series (Fig. 1) is. Is referred to as sialic acid GSL , GM3 synthase (sialic acid transferase I: SAT-I) synthesized from lactosylceramide (LacCer) by GM3 (Fig. 1) and the starting point. Which is an initial stage of the biosynthetic pathway GSL glucosylceramide (GlcCer) biosynthesis enzyme inhibitors include, non-patent document 1 D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-threo-PDMP) (), (1R,2R) -nonanoic acid[ 2-(2,3-dihydro-benzo [1,4] dioxin-6-yl) -2-hydroxy-1-pyrrolidin-1-ylmethyl-ethyl]-amide-l-tartaric acid salt (Genz-123346) D-threo-PDMP of the analog, and the like N-(5-adamantane-1-yl-methoxy) -pentyl-1-deoxynojirimycin (AMP-DNM). These inhibitors is, obese model animal and in vitro to improve insulin resistance, can have an effect of improving fatty liver, further serum triglyceride, free fatty acids (and cholesterol in bile from the liver is reduced such as to promote excretion of cholesterol into (i.e. activation of the reverse cholesterol transfer system) or the like has been reported (non-patent document 2-7), the clinical application aiming at the development is in progress.
However, in the knockout mouse of the glucosylceramide synthase is embryonic lethal since were reported to be (non-patent document 8), inhibitor of this enzyme is a fear that it could potential side effects. On the other hand, the lifetime of the knockout mouse of the GM3 synthase to be comparable to the wild-type (non-patent document 9) from the, adverse effects caused by inhibition of GM3 synthase is of little expected.
Organ responsible for insulin (muscle, liver and adipose tissue) is expressed GSL, glucosylceramide (GlcCer), lactosylceramide (LacCer), ganglioside GM3 and GM2 as in a wide variety. Yamashita et al. GM3 synthase (SAT-I) gene defect in the mice and, in these mice, shown in Fig. 1 a- and b- series ordinarily not express gangliosides, as well as a high-fat diet load at the onset of insulin resistance as compared to wild-type mice, SAT-I deficient mice in alleviating insulin resistance are reported (non-patent document 9).
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  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
  • 発明者(英語)
  • INOKUCHI Jinichi
  • NAGAFUKU Masakazu
  • HAYAMIZU Hirotaka
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IS JP KE KG KM KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PE PG PH PL PT RO RS RU SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ MD RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG
参考情報 (研究プロジェクト等) CREST Clarification of the Biological Functions of Sugar Chains and the Use of this Knowledge in Applied Technologies AREA
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