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Aβ-PROTEIN-SPECIFIC PRODUCTION INHIBITOR NEW

外国特許コード F200010163
整理番号 (S2018-0917-N0)
掲載日 2020年6月3日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2019JP032345
国際公開番号 WO 2020040106
国際出願日 令和元年8月20日(2019.8.20)
国際公開日 令和2年2月27日(2020.2.27)
優先権データ
  • 特願2018-154788 (2018.8.21) JP
発明の名称 (英語) Aβ-PROTEIN-SPECIFIC PRODUCTION INHIBITOR NEW
発明の概要(英語) Provided is a compound that specifically inhibits the production of Aβ protein and serves as an active component of a drug for treating and/or preventing Alzheimer's disease. The Aβ-protein-specific production inhibitor according to the present invention is characterized by containing a peptide (FGBTWDYWVYRRR, where B is an L-4,4'-biphenylalanine residue) that comprises an amino acid sequence set forth in SEQ ID NO: 1 and inhibits both β-secretase and γ-secretase activity. A peptide comprising the amino acid sequence set forth in SEQ ID NO: 1 can be utilized in the prevention and/or treatment of Alzheimer's disease.
従来技術、競合技術の概要(英語) BACKGROUND ART
Dementia is 85 years or more of the common disease onset of about 25% Japanese port is, which occupies about a half of the Alzheimer's disease are (Alzheimer's disease). Alzheimer's disease, cognitive decline or a change in the persona and the major symptoms of dementia is one. More than 300 million current Japan is Alzheimer's disease patients is estimated, in accordance with the aging of the future an increasing number of patients to follow.
As a mechanism of the onset of Alzheimer's disease amyloid cascade theories have been proposed. Amyloid cascade is, an age-associated amyloid accumulation the trigger, the inflammatory response, in the nerve cells of abnormal protein Tau is accumulated, and finally is the neuronal dysfunction (cell death) modified to name the complex path. That is, non-patent document 1 and non-patent document 2 as described, the A β protein, cell transmembrane protein amyloid precursor protein (hereinafter, referred to herein as APP.) Is cut by the β-secretase cell transmembrane protein (C99) is β CTF, γ-secretase further released from the cell membrane by cutting, and in the brain is believed to be stored.
A β γ-secretase protein is cut at C99, and the AICD are known and can be divided into, are cut by the APP secretase β, are also known that free sAPP β (Fig. 1).
From the above, β and γ-secretase inhibitors of beta-secretase inhibitor, Alzheimer's disease is a protein, protein A β exhibit an effect of suppressing the accumulation of the considered agent.
However, each of the transmembrane protein Pen-2, presenilin, secretase, and is known as a complex comprising Aph-1 γ-secretase is, belong to the aspartic protease, such as the above-mentioned APP APLP1,APLP2,Notch,Jagged2,Delta1,E-cadherin,N-cadherin,CD44,ErbB4,Nectin1,LRP1 as well as the transmembrane protein, receptor substrate for proteases and the like.
Therefore, the production of a protein A β in order to obtain a suppression effect of the γ-secretase inhibitor, L-685,458,DAPT,LY-411,575 such as the use of, other than the γ-secretase C99 described above with respect to a protein of the enzyme activity of the protease but also restrains, such inhibitors as it is used as an agent, such as side effects to be feared.
For example, γ-secretase inhibitors of 1 is one of the LY-411,575, thymus atrophy in the spleen and mature B cells to reduce the number of cells have been reported and the like, such an inhibitor in a pharmaceutical composition as, can cause a side effect of the immune or the like is suggested (Non-Patent Document 3). In addition, γ-secretase enzyme activity itself is reduced, an abnormality of the skin, squamous cell carcinomas, spleen enlargement of the cause or the like has been reported (Non-Patent Document 4).
Non-steroidal anti-inflammatory drugs (hereinafter, referred to herein as NSAIDs.) Is effective as an inhibitor in the production of a protein A β is found to be present such as, a number of familial Alzheimer's disease (for example, an isolated variant of the case.) Is, no effect has been known (Non-Patent Document 5). Further mild cognitive impairment and Alzheimer's disease and γ-secretase activity is separated from the patient and change, the effect of reducing the Aβ42 γ secretase model dju aerator found to be lower (non-patent document 6).
Also, the extracellular region of the N end β CTF FLAG tag to the case where the expression, the presence of the anti-FLAG antibody, γ-secretase degradation of the (non-patent document 7) is not.
Patent Document 1 is 2 and, γ-secretase protein cut characteristics of the focusing (length), γ-secretase (C99) is used as the basis of protein A β end portion of the captured by cutting, to produce focusing A β, then, is to be attached to the tip of the reagent C99 (C99 binding peptides) bepuchido developed, the effect was examined and, γ-secretase is not possible to catch an end portion of the C99, the cutting may not be described.
  • 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
  • THE DOSHISHA
  • 発明者(英語)
  • FUNAMOTO SATORU
  • NOBUHARA MIKA
  • KAWAMURA SEIKO
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JO JP KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA 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 RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ 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 KM ML MR NE SN ST TD TG

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