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COMPOUND FOR IMPROVING CELL TRANSPLANTATION EFFICIENCY

外国特許コード F200010072
整理番号 5965
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 2019JP011320
国際公開番号 WO 2019181901
国際出願日 平成31年3月19日(2019.3.19)
国際公開日 令和元年9月26日(2019.9.26)
優先権データ
  • 特願2018-053515 (2018.3.20) JP
発明の名称 (英語) COMPOUND FOR IMPROVING CELL TRANSPLANTATION EFFICIENCY
発明の概要(英語) The purpose of the present invention is to provide a compound that acts to inhibit anoikis in cells and enhance cell survival rates, and a compound that induces cell infiltration and enhances cell engraftment. The present invention provides a compound represented by formula (I) or a salt thereof. [In the formula, ring A1 and ring A2 are the same or different and represent a substitutable six-membered aromatic heterocyclic group having 1–3 nitrogen atoms, R1 represents formyl or hydroxymethyl, and R2 is a group represented by -L-(X1)n-(X2)m-(X3)p-NH2 (in the formula: L represents a linker; n represents 0, 1, or 2; m represents 2 or 3; p represents 0, 1, 2, or 3; X1 and X3 each independently represent an amino acid residue selected from among Ser, Ala, Gly, Lys, Val, Leu, Ile, Thr, Cys, Met, Asn, Gln, Pro, Asp, Glu, Arg, His, and Orn; and the X2 radicals are the same or different and represent an amino acid residue selected from among Phe, Tyr, and Trp).]
従来技術、競合技術の概要(英語) BACKGROUND ART
Cell therapy, regenerative medicine is, useful for the treatment of cells implanted into the body. Cell therapy in one of the problems of low efficiency cells. Many of the implanted cells after injection to a patient, cannot be live, only a small percentage of cells to be viable, to achieve the desired therapeutic effect in a large number of cells is required.
Cells is one cause of low efficiency, when the cell transplantation, cells are separated from the extracellular matrix, cell death (apoptosis) is a high probability of occurring. Cells and extracellular matrix adhesion between the cell death induced by loss or abnormality ' (anoikis) anoikis' is called.
To this, inhibiting anoikis, to promote adhesion and growth of cultured cells of the small molecular weight compound, represented by the following formula has been found (adhesamine) adhesamine (Non-Patent Document 1, Patent Document 1).
Syndecan is, the core through the cell membrane in the cell membrane heparan sulfate proteoglycans. Of the core 1 due to differences in thin decane, 2, 3, 4 and 4 of known type, heparan sulfate and chondroitin sulfate having 2 kinds of sugar side chains of the mixed type proteoglycan. Syndecan is via the sugar chains heparan sulfate, or extracellular matrix components such as fibroblast growth factor and growth factor and interaction, and movement of the adhesion to the extracellular matrix, such as between cells contribute to the recognition. By previous studies, adhesamine is, the surface of the cells by binding of heparan sulfate syndecan, floating in the suspension to promote adhesion and growth of the cells has been found.
In addition, the interaction between involved in cell adhesion and, through the cell membrane is integrin receptors, extracellular matrix proteins such as fibronectin and the specific amino acid sequence of recognizing and binding to the RGD. Inhibits anoikis as another compound, and the conjugate of the integrin-binding peptide RGDS adhesamine Adh-RGDS been reported (see Fig. 1b) (Non-Patent Document 2, Patent Document 2). Fibronectin is an extracellular matrix protein, an integrin binding sites and binding sites of heparan sulfate is both. Both in cooperation with the site, prompt cell survival fibronectin to induce a stronger signal. Integrin binding site (RGDS) Adh-RGDS and heparan sulfate binding site has both of, fibronectin stronger than the effect to improve cell viability.
  • 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
  • TOKYO UNIVERSITY OF SCIENCE FOUNDATION
  • 発明者(英語)
  • UESUGI, Motonari
  • TAKASHIMA, Ippei
  • NISHIKAWA, Makiya
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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