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METHOD FOR SCREENING BINDING INHIBITOR OF RAGE AND AGE コモンズ

外国特許コード F120006980
整理番号 S2010-1251-C0
掲載日 2012年10月29日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2011JP071669
国際公開番号 WO 2012039469
国際出願日 平成23年9月22日(2011.9.22)
国際公開日 平成24年3月29日(2012.3.29)
優先権データ
  • 特願2010-214019 (2010.9.24) JP
発明の名称 (英語) METHOD FOR SCREENING BINDING INHIBITOR OF RAGE AND AGE コモンズ
発明の概要(英語) Provided is a method for screening a binding inhibitor of RAGE and AGE focused on the new activity of β-amyloid peptide. Provided is a method for screening a binding inhibitor of RAGE and AGE by sorting candidate compounds inhibiting the activity affecting the binding affinity of RAGE and AGE of β-amyloid peptide through finding, for the first time, that the β-amyloid peptide makes the binding of RAGE and AGE change to high binding affinity. The binding inhibitor obtained by this screening method can be used as a therapeutic agent for any diseases or symptoms caused by the binding of RAGE and AGE in which β-amyloid peptide involves. Especially, the binding inhibitor is capable of contributing to the development of the therapeutic drug for Alzheimer's disease focused on the new mechanism.
従来技術、競合技術の概要(英語) BACKGROUND ART
(Alzheimer's disease) is Alzheimer's disease, progressive neurological disorder of cognitive function and adversely affected, falling off of the cerebral nerve cells of the considered for developing. For the genesis of Alzheimer's disease, β - amyloid peptide is the most promising current theory. This theory is, a so-called senile plaques in Alzheimer's disease brain structure of the modified protein deposition has been found that a large number of, as the important constituents of neuritic plaques, β - amyloid peptide has been identified, the analysis of familial Alzheimer's disease have been found in the amyloid precursor protein (Amyloid Precursor Protein: APP) and presenilin 1/2(Presenillin 1/2) variants, increased production of β - amyloid peptides can act to be known, β - amyloid β oligomer or a further polymer sheet structure has a neurotoxic effects are based on the findings.
From the knowledge as described above, suppress production of β - amyloid in the brain, promote metabolism, anti-β - amyloid peptide antibody, amyloid β - oligomerization, polymerization inhibitor is continued to be developed. For example, Alzheimer's disease β - amyloid peptide inhibiting the formation of the therapeutic compound is disclosed (new ginsenosides compound) (Patent Document 1: Japanese Patent Application JP-2008-506686). Β - amyloid protein in Alzheimer's disease and other disorders of the fibril formation of low molecular weight peptides for the treatment of is disclosed (Patent Document 2: Japanese Patent Application JP-2007-535494). To suppress the flocculation of the amyloid protein and the material for the action, lipocalin-type prostaglandin D synthase (L-PGDS) is focused on the disclosure of which is for the agent (Patent Document 3: Japanese Patent Application Laid-open 2007-284351). Β - amyloid peptide and Alzheimer's disease using the method of screening a therapeutic or prophylactic agent is disclosed (Patent Document 4: Japanese Patent Application Laid-open 2006-265189). In addition, as a screening method for the therapeutic agent of Alzheimer's disease, amyloid-β - (1-40) activity as an index for the transport of those is also disclosed (Patent Document 5: Patent Publication 4270976). Otherwise, the β - amyloid peptide, β-secretase or γ secretase amyloid precursor protein and that is generated by the action of the β secretase (BACE) focused on the γ secretase inhibitors or inhibitors, β - amyloid peptide antibody is an anti - β - amyloid peptide itself has been developed (see Fig. 1). However, such an effort has been made in spite of the inventors, is a promising potential new not available in the market.
Β - amyloid peptide is, its own as a oligomer or polymer fibers to form a halide, and is operative for a certain type of receptor structure, the neurotoxin is believed to be exhibited. Is mentioned as one of the receptor, is RAGE(Receptor for advanced glycation endproducts). This receptor, a receptor for AGE(advanced glycation endproducts) as the name implies has been identified as, RAGE ligand β - amyloid peptide in vivo may be considered to be one of the (non-patent document 1-3). AGE is, a reducing sugar and a protein non-enzymatic saccharization reaction (also referred to as the Maillard reaction) is generated in the late stages of the structure (see Fig. 2) is a general term. AGE and RAGE is, as well as the vascular complications of diabetes, arteriosclerosis, tumor growth, metastasis, inflammatory response is also involved in Alzheimer's disease has been bright et al. In addition, the test tube by AGE and RAGE-binding experiments for the assay method (measurement method) has been reported (Non-Patent Document 4). However, in relation to amyloid β - RAGE, involved in Alzheimer's disease may be determined based on how the, has been solved sufficiently less.
  • 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
  • NATIONAL UNIVERSITY CORPORATION OKAYAMA UNIVERSITY
  • 発明者(英語)
  • NISHIBORI, Masahiro
  • MORI, Shuji
  • TAKAHASHI, Hideo
  • WAKE, Hidenori
  • LIU, Keyue
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 QA RO RS RU RW 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

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