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PHARMACEUTICAL COMPOSITION TARGETING RUNX BINDING SEQUENCE, AND RUNX INHIBITOR

外国特許コード F200010055
整理番号 6111
掲載日 2020年5月15日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2019JP020961
国際公開番号 WO 2019230669
国際出願日 令和元年5月27日(2019.5.27)
国際公開日 令和元年12月5日(2019.12.5)
優先権データ
  • 特願2018-101788 (2018.5.28) JP
発明の名称 (英語) PHARMACEUTICAL COMPOSITION TARGETING RUNX BINDING SEQUENCE, AND RUNX INHIBITOR
発明の概要(英語) The present invention provides: an antitumor composition and an antiallergy composition comprising a pyrrole-imidazole polyamide capable of binding to a RUNX binding sequence, one or more pyrrole units that constitute the pyrrole-imidazole polyamide being substituted by β-alanine; and a RUNX inhibitor.
従来技術、競合技術の概要(英語) BACKGROUND ART
Runt-related transcription factor (Runt-related transcription factor: hereinafter, abbreviated as' RUNX ') family, blood-related gene and the expression of the gene to hematopoietic stem cell-associated transcription factor control is important. RUNX is a member of a family, RUNX1, RUNX2, RUNX3 and which, like the secondary hematopoietic RUNX1, such as the development of bone RUNX2, RUNX3 is nerve, thymus cell proliferation are known to be involved or the like. RUNX each member of the family, core-binding factor (CBF β) β subunit heterodimers and form a complex. RUNX is, runt domain via, the transcriptional regulatory region of the target gene in the consensus binding sequence 5 '- TGTGGT-3', is a very rare and 5 '- TGCGGT-3' is recognized, by coupling, to control the expression of target genes. On the other hand, the CBF β, to adjust the non-DNA binding subunit. CBF β is, allosterically RUNX to enhance binding of the DNA.
RUNX1 is, (AML1) acute myeloid leukemia 1 also known as protein, leukemia tumor suppressor is believed that in the development. On the other hand, recent study, acute myelogenous leukemia (AML) RUNX1 in the development of tumor formation characteristics are suggested to have, for the purpose of the treatment of leukemia, RUNX1 CBF β and low molecular weight compound that inhibits binding between the two studies have been reported (Non-Patent Document 1). However, until now, for the treatment of leukemia as well as a variety of cancers, the target binding sites on the DNA genome RUNX family of attempts has not been reported.
On the other hand, a pyrrole-imidazole polyamide (hereinafter, 'PI polyamide' abbreviated) is, and a synthetic oligomer, a hairpin (P) connected to the facing by pyrrole and imidazole (I) pair, in the minor groove of DNA bound to recognize a particular sequence is known. PI polyamide, C pair P/I, pair of base g, P/P a pair of the A, T or T, the base pair A, pair I/P g, C recognized base pairs, the double stranded DNA sequences by which any can be coupled to specific. Therefore, a variety of orders can be designed to be a pair of P/I, to the target site on the genome of the desired PI in vivo delivery of the polyamide becomes possible.
PI polyamide is, in spite of its relatively large molecular weight, and the cell membrane permeability, localized in the nucleus of the cell, in the nanomolar affect the expression of an endogenous gene. PI polyamide is coupled to the target gene, transcription factors and to inhibit the binding of DNA, a gene specific gene expression has been studied as a switch. Further, in recent years studies of the inventors of the present invention, targeted PI RUNX family of polyamide, polyamide and an alkylating agent such as the PI of the conjugated compound, and using the conjugate anti-tumor agent (Patent Document 1) has been reported.
  • 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
  • KYOTO UNIVERSITY
  • 発明者(英語)
  • SUGIYAMA, Hiroshi
  • KAMIKUBO, Yasuhiko
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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