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APOPTOSIS INDUCER

Foreign code F110005354
File No. S2011-0187-N0
Posted date Sep 2, 2011
Country WIPO
International application number 2010JP064857
International publication number WO 2011025050
Date of international filing Aug 25, 2010
Date of international publication Mar 3, 2011
Priority data
  • P2009-194747 (Aug 25, 2009) JP
Title APOPTOSIS INDUCER
Abstract Disclosed are: an apoptosis inducer which can induce the apoptosis of various types of cells including tumor cells conveniently; and others. The apoptosis inducer is characterized by comprising a peptide (a) or (b) as mentioned below, a derivative of the peptide, or a salt of the peptide or the derivative: (a) a peptide comprising the amino acid sequence represented by formula (I): C-X-D-X-X-X-X-Y-X-C-X-C; and (b) a peptide which comprises an amino acid sequence produced by deleting, substituting or adding one or several amino acid residues in the amino acid sequence represented by the above-mentioned formula (I) and which has an apoptosis-inducing activity.
Outline of related art and contending technology BACKGROUND ART
Apoptosis, and one of the forms of cell death, disruption of the nucleus within a cell refers to cell death. Up to now, as the molecular mechanisms of apoptosis in cancer cells death, calcium pathway, death signaling pathway, ceramide pathway, mitochondrial, 5 and p53 of the apoptotic pathway is induced in the path of the two known molecular mechanisms (for example, 'Hashimoto yoshiyuki, new apoptosis molecular medicine, sheep earth Inc., 4 年 2001, pages 10-58' reference). A substance which induces apoptosis are known and many, such as mitomycin and taxol in clinical medicine and the anti-cancer agent is used. These artificial other than, or on a living body such as TNF α FasL (Fas ligand) protein exists in the induction of apoptosis. These artificial, natural apoptosis-inducing substances, such as cancer cells which are harmful to humans can be lethal to cells. As described above, also the anti-cancer agent used in chemotherapy, gene therapy also FasL being advanced studies, and applying this principle. Chemotherapy with, side effects to healthy tissue obstructs a portion of the treatment, effect on the lesion with the expectation that only, a gene therapy using gene transfer into the lesion has been studied. However, actually in the gene-introduced cells will, typically, a portion of the cells and the lesion, the cells were subsequently introduced a gene killed condition, a therapeutically effective protein or the like is not produced more of cells, as a result, the effect of the partial gene therapy in many cases. Therefore, the remaining of the pathological cells, it is required to repeatedly for gene transfer. In addition, the first gene by the introduction of the gene is introduced into the cells which were not, not easily HBlOl and there, the treatment is hindered.
In such a situation, various tumor cells to the cell can be easily induced apoptosis in the development of apoptosis-inducing agents has been desired. The present invention is, in consideration of the above circumstances with an object, shown below, inducer of apoptosis, pharmaceutical composition for the treatment of cancer and the like system according to the invention. (1) (A) or (b) the following peptides, derivatives or salts thereof characterized in that, apoptosis-inducing agents. (a) The following formula (I): (X is any amino acid residues, is a cysteine represents C, D represents an aspartic acid, phenylalanine is F.) A peptide comprising the amino acid sequence. (b) Amino acid sequence represented by the above formula (I) or an amino acid sequence in the 1 deletion, substitution or addition of the amino acid sequence, and, a peptide having apoptosis-inducing activity. In the above- (1) inducing agent, the amino acid sequence shown in formula (I), for example, SEQ ID NO:2 or amino acid sequence shown in SEQ ID NO and 3. In addition, the peptides of (a), for example, shown in SEQ ID NO:5 or SEQ ID NO:7 and comprising an amino acid sequence. (2) In a cell of interest to the above-mentioned (1) cells or cell populations comprising the action of the inducing agent, apoptosis-inducing method. In the method of induction, wherein the step of, for example, the cells of interest or cell population and the step of contacting the inducing agent. (3) The (1) inducing agent, a pharmaceutical composition for the treatment of cancer.
Scope of claims (In Japanese)請求の範囲 [請求項1]
以下の(a)又は(b)のペプチド、その誘導体又はこれらの塩を含むことを特徴とする、アポトーシス誘導剤。
 (a)下記式(I):

 (Xは任意のアミノ酸残基を表し、Cはシステインを表し、Dはアスパラギン酸を表し、Fはフェニルアラニンを表す。)
で示されるアミノ酸配列を含むペプチド。
 (b)上記式(I)で示されるアミノ酸配列において1若しくは数個のアミノ酸が欠失、置換若しくは付加されたアミノ酸配列を含み、かつ、アポトーシス誘導活性を有するペプチド。

[請求項2]
前記式(I)で示されるアミノ酸配列が、配列番号2又は配列番号3に示されるアミノ酸配列である、請求項1記載の誘導剤。

[請求項3]
前記(a)のペプチドが、配列番号5又は配列番号7に示されるアミノ酸配列を含むペプチドである、請求項1又は2記載の誘導剤。

[請求項4]
目的の細胞又は細胞集団に対して請求項1~3のいずれか1項に記載の誘導剤を作用させる工程を含む、アポトーシス誘導方法。

[請求項5]
前記工程が、目的の細胞又は細胞集団に前記誘導剤を接触させる工程である、請求項4記載の方法。

[請求項6]
請求項1~3のいずれか1項に記載の誘導剤を含む、癌の治療用医薬組成物。

  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • NIHON UNIVERSITY
  • Inventor
  • HIDAI, Chiaki
  • KITANO, Hisataka
IPC(International Patent Classification)
Specified countries 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 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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