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METHOD FOR INHIBITING PROLIFERATION OF HIGH LIX1L-EXPRESSING TUMOR CELL, AND TUMOR CELL PROLIFERATION-INHIBITING PEPTIDE

Foreign code F150008327
Posted date Apr 22, 2015
Country WIPO
International application number 2014JP059780
International publication number WO 2014168064
Date of international filing Apr 2, 2014
Date of international publication Oct 16, 2014
Priority data
  • P2013-082272 (Apr 10, 2013) JP
  • P2013-173696 (Aug 23, 2013) JP
Title METHOD FOR INHIBITING PROLIFERATION OF HIGH LIX1L-EXPRESSING TUMOR CELL, AND TUMOR CELL PROLIFERATION-INHIBITING PEPTIDE
Abstract A method for inhibiting the proliferation of high LIX1L-expressing tumor cells characterized in that the expression or function of the LIX1L gene is limited in tumor cells that are expressing LIX1L gene at a high level.
Outline of related art and contending technology BACKGROUND ART
The current, the anti-tumor agent used for malignant tumor, anti-metabolites (Ara-C, methotrexate and the like), plant alkaloids (vincristine), alkylating agents (endoxan), anti-cancer antibiotics (adriamycin, idarubicin mitomycin and the like), such as platinum (cisplatin) formulation, there are many known. Among them, polypeptide agents include, human interferon - γ polypeptide (for example, see Patent Document 1.) Or, human tumor necrosis factor (TNF) or converts it from one part of the polypeptide (for example, see Patent Document 2.) And the like. Particularly in recent years, a high molecular target therapeutic tumor specificity (imatinib or the like), and the like (such as rituximab) monoclonal antibody was remarkable progress, has been high therapeutic effect. However, the anti-tumor agent such as imatinib, narrow spectrum anti-tumor effect, the tumor must be in selection of a drug for each addition, the problem of drug resistance. For this reason, at all times in the medical field, a wide spectrum anti-tumor effect more effective drug is demanded.
On the other hand, human LIX1L (Lix1 homolog-like, may be referred to as hLIX1L or less.) Gene, 337 amino acids in the LIX1L structural gene encoding the protein. LIX1L Has still molecular biological role is unknown, its expression amount varies depending on the cell types have been reported. Patent Document 3 is for example, LIX1L gene, activated by an agonist for the AhR CYP1A1 is directed to a compound that is sensitive to the sensitivity of the cells in a cell not, statistically significant differences in the expression (P<1.0x10-5) is present among the 266 genes were reported to be one of the 1 are. In addition, in Patent Document 4, in accordance with the allergy increases or decreases the expression levels of large numbers of genes as one group of LIX1L genes listed in the table 1.
Scope of claims (In Japanese)請求の範囲 [請求項1]
 LIX1L遺伝子を高発現している腫瘍細胞に対して、LIX1L遺伝子の発現又は機能を抑制させる、LIX1L高発現腫瘍細胞の増殖阻害方法。

[請求項2]
 RNA干渉によりLIX1L遺伝子の発現を抑制する、請求項1に記載のLIX1L高発現腫瘍細胞の増殖阻害方法。

[請求項3]
RNA干渉によりLIX1L遺伝子の発現を抑制することが、配列番号3又は4で表される塩基配列を含むshRNA若しくはsiRNA、又は前記shRNA若しくは前記siRNAを細胞内で生産するベクターを細胞内に導入すること、を含む、請求項2に記載のLIX1L高発現腫瘍細胞の増殖阻害方法。

[請求項4]
 LIX1L蛋白質のチロシンのリン酸化を阻害することを含む、請求項1に記載のLIX1L高発現腫瘍細胞の増殖阻害方法。

[請求項5]
 前記チロシンが、配列番号1で表されるアミノ酸配列からなるLIX1L蛋白質の136番目のチロシンである、請求項4に記載のLIX1L高発現腫瘍細胞の増殖阻害方法。

[請求項6]
 配列番号1で表されるアミノ酸配列の部分配列であって、136番目のチロシンを含む部分配列からなるポリペプチドを含む、腫瘍細胞増殖抑制ペプチド。

[請求項7]
 前記136番目のチロシンを含む部分配列からなるポリペプチドと、細胞膜透過能を有する部位とが、直接又は間接的に結合している、請求項6に記載の腫瘍細胞増殖抑制ペプチド。

[請求項8]
 前記136番目のチロシンを含む部分配列が、8個以上、35個以下のアミノ酸からなる、請求項6又は7に記載の腫瘍細胞増殖抑制ペプチド。

[請求項9]
 前記細胞膜透過能を有する部位が、配列番号7で表されるアミノ酸配列からなるペプチドである、請求項7又は8に記載の腫瘍細胞増殖抑制ペプチド。

[請求項10]
 請求項6~9のいずれか一項に記載の腫瘍細胞増殖抑制ペプチドを有効成分とする医薬用組成物。

[請求項11]
 抗腫瘍剤である、請求項10に記載の医薬用組成物。

[請求項12]
 請求項6~9のいずれか一項に記載の腫瘍細胞増殖抑制ペプチドを、LIX1L高発現腫瘍細胞に導入すること、を含む、LIX1L高発現腫瘍細胞の増殖阻害方法。

[請求項13]
LIX1L蛋白質のチロシンのリン酸化を阻害することを含むリン酸化阻害剤。

[請求項14]
前記チロシンが、配列番号1で表されるアミノ酸配列からなるLIX1L蛋白質の136番目のチロシンである、請求項13に記載のリン酸化阻害剤。

  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • NATIONAL UNIVERSITY CORPORATION HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE
  • Inventor
  • NAKAMURA Satoki
  • SUGIMURA Haruhiko
IPC(International Patent Classification)
Specified countries 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 DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JP KE KG 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 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 TD TG
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