Title:
SYNTHESIS AND ANALYSIS OF NOVEL COMPOUND CAPABLE OF INDUCING DIFFERENTIATION OF HUMAN MESENCHYMAL STEM CELL INTO HEPATOCYTE
Document Type and Number:
WIPO Patent Application WO/2012/141038
Kind Code:
A1
Abstract:
The purpose is to select a low-molecular-weight compound which is effective for inducing the differentiation of a mesenchymal stem cell into a hepatocyte and develop a differentiation-inducing method which has excellent efficiency of inducing a mesenchymal stem cell into a hepatocyte and is safe. At least one compound selected from compounds represented by formula (1) and formula (2), a salt of the compound, or a solvate of the compound or the salt; a differentiation-inducing agent comprising at least one compound selected from compounds represented by formula (1) and formula (2), a salt of the compound, or a solvate of the compound or the salt; and a differentiation-inducing agent comprising a compound represented by formula (8), a salt of the compound or a solvate of the compound or the salt.
Inventors:
SHIOTA GOSHI (JP)
HOSHIKAWA YOSHIKO (JP)
MATSUMOTO NORIKO (JP)
MATSUMI YOSHIRO (JP)
MORIMOTO MINORU (JP)
TONOI TAKAYUKI (JP)
SAIMOTO HIROYUKI (JP)
OHASHI KAZUO (JP)
OKANO TERUO (JP)
HOSHIKAWA YOSHIKO (JP)
MATSUMOTO NORIKO (JP)
MATSUMI YOSHIRO (JP)
MORIMOTO MINORU (JP)
TONOI TAKAYUKI (JP)
SAIMOTO HIROYUKI (JP)
OHASHI KAZUO (JP)
OKANO TERUO (JP)
Application Number:
PCT/JP2012/059021
Publication Date:
October 18, 2012
Filing Date:
April 02, 2012
Export Citation:
Assignee:
NAT UNIV CORP TOTTORI UNIV (JP)
UNIV TOKYO WOMENS MEDICAL (JP)
SHIOTA GOSHI (JP)
HOSHIKAWA YOSHIKO (JP)
MATSUMOTO NORIKO (JP)
MATSUMI YOSHIRO (JP)
MORIMOTO MINORU (JP)
TONOI TAKAYUKI (JP)
SAIMOTO HIROYUKI (JP)
OHASHI KAZUO (JP)
OKANO TERUO (JP)
UNIV TOKYO WOMENS MEDICAL (JP)
SHIOTA GOSHI (JP)
HOSHIKAWA YOSHIKO (JP)
MATSUMOTO NORIKO (JP)
MATSUMI YOSHIRO (JP)
MORIMOTO MINORU (JP)
TONOI TAKAYUKI (JP)
SAIMOTO HIROYUKI (JP)
OHASHI KAZUO (JP)
OKANO TERUO (JP)
International Classes:
A61L27/00; C07C251/86; C07C43/225; C07D307/52; C07D487/04; C12N5/071
Foreign References:
| JP2010523579A | 2010-07-15 | |||
| JP2007503816A | 2007-03-01 | |||
| JP2011219435A | 2011-11-04 | |||
| JP2009535035A | 2009-10-01 | |||
| JP2010075631A | 2010-04-08 | |||
| JP2009060840A | 2009-03-26 |
Other References:
YOSHIAKI MATSUMI ET AL.: "Hito Kotsuzui Yurai Kan'yo-kei Kansaibo o Kinosei Kansaibo e Bunka Yudo Sayo o Motsu Wnt/p-catenin Signal Yokuseisei Teibunshi Kagobutsu no Dotei ni yoru Kan Saisei Iryo Kaihatsu", ACTA HEPATOLOGICA JAPONICA, vol. 51, no. 1, 30 April 2010 (2010-04-30), pages A259, XP008171762
ATSUSHI YANAGITANI ET AL.: "Retinoic Acid Receptor Dominant Negative Form Causes Steatohepatitis and Liver Tumors in Transgenic Mice", HEPATOLOGY, vol. 40, no. 2, 2004, pages 366 - 375, XP055298794, DOI: doi:10.1002/hep.20335
SEOYOUNG PARK ET AL.: "Hexachlorophene Inhibits Wnt/j3-Catenin Pathway by Promoting Siah-Mediated [3-Catenin Degradation", MOL PHARMACOL, vol. 70, no. 3, 2006, pages 960 - 966, XP002492545, DOI: doi:10.1124/mol.106.024729
YOKO YOSHIDA ET AL.: "A role of Wnt/j3-catenin signals in hepatic fate specification of human umbilical cord blood-derived mesenchymal stem cells", AM J PHYSIOL GASTROINTEST LIVER PHYSIOL, vol. 293, 2007, pages G1089 - G1098, XP055156094, DOI: doi:10.1152/ajpgi.00187.2007
SHIMOMURA T ET AL.: "Hepatic differentiation of human bone marrow-derived UE7T-13 cells: Effects of cytokines and CCN family gene expression", HEPATOL RES., vol. 37, 2007, pages 1068 - 79
ISHII K ET AL.: "Hepatic differentiation of human bone marrow-derived mesenchymal stem cells by tetracycline-regulated hepatocyte nuclear factor 3 beta", HEPATOLOGY, vol. 48, 2008, pages 597 - 606
MAINA LEPOURCELET ET AL.: "Small-molecule antagonists of the oncogenic Tcf/?-catenin protein complex", CANCER CELL, vol. 5, January 2004 (2004-01-01), pages 91 - 102, XP002984831, DOI: doi:10.1016/S1535-6108(03)00334-9
EMAMI KH ET AL.: "A small molecule inhibitor of beta-catenin/CREB-binding protein transcription", PROC NATL ACAD SCI U S A., vol. 101, no. 34, 24 August 2004 (2004-08-24), pages 12682 - 7, XP002699746, DOI: doi:10.1073/pnas.0404875101
JUFANG SHAN ET AL.: "Identification of a Specific Inhibitor of the Dishevelled PDZ Domain", BIOCHEMISTRY, vol. 44, no. 47, 29 November 2005 (2005-11-29), pages 15495 - 503
TROSSET JY ET AL.: "Inhibition of protein-protein interactions: the discovery of druglike beta-catenin inhibitors by combining virtual and biophysical screening", PROTEINS, vol. 64, no. 1, 1 July 2006 (2006-07-01), pages 60 - 7, XP055186061, DOI: doi:10.1002/prot.20955
BERGE, BIGHLEY; MONKHOUSE, J. PHARM. SCI., vol. 66, 1977, pages 1 - 19
J. HONIG ET AL.: "The Van Nostrand Chemist's Dictionary", 1953, pages: 650
T. HIGUCHI; V. STELLA: "A.C.S. Symposium Series", vol. 14, article "Pro-Drugs as Novel Delivery Systems"
"Chemistry And Drug Discovery", vol. 1, article "Principles and Practice"
DRUG DISCOV. TODAY, vol. 10, 2005, pages 1467 - 1474
TETRAHEDRON, vol. 63, 2007, pages 12912 - 12916
AMERICAN JOURNAL OF TRANSPLANTATION, vol. 6, 2006, pages 50 - 59
NATURE MEDICINE, vol. 13, no. 7, 2007, pages 880 - 885
See also references of EP 2698365A4
ATSUSHI YANAGITANI ET AL.: "Retinoic Acid Receptor Dominant Negative Form Causes Steatohepatitis and Liver Tumors in Transgenic Mice", HEPATOLOGY, vol. 40, no. 2, 2004, pages 366 - 375, XP055298794, DOI: doi:10.1002/hep.20335
SEOYOUNG PARK ET AL.: "Hexachlorophene Inhibits Wnt/j3-Catenin Pathway by Promoting Siah-Mediated [3-Catenin Degradation", MOL PHARMACOL, vol. 70, no. 3, 2006, pages 960 - 966, XP002492545, DOI: doi:10.1124/mol.106.024729
YOKO YOSHIDA ET AL.: "A role of Wnt/j3-catenin signals in hepatic fate specification of human umbilical cord blood-derived mesenchymal stem cells", AM J PHYSIOL GASTROINTEST LIVER PHYSIOL, vol. 293, 2007, pages G1089 - G1098, XP055156094, DOI: doi:10.1152/ajpgi.00187.2007
SHIMOMURA T ET AL.: "Hepatic differentiation of human bone marrow-derived UE7T-13 cells: Effects of cytokines and CCN family gene expression", HEPATOL RES., vol. 37, 2007, pages 1068 - 79
ISHII K ET AL.: "Hepatic differentiation of human bone marrow-derived mesenchymal stem cells by tetracycline-regulated hepatocyte nuclear factor 3 beta", HEPATOLOGY, vol. 48, 2008, pages 597 - 606
MAINA LEPOURCELET ET AL.: "Small-molecule antagonists of the oncogenic Tcf/?-catenin protein complex", CANCER CELL, vol. 5, January 2004 (2004-01-01), pages 91 - 102, XP002984831, DOI: doi:10.1016/S1535-6108(03)00334-9
EMAMI KH ET AL.: "A small molecule inhibitor of beta-catenin/CREB-binding protein transcription", PROC NATL ACAD SCI U S A., vol. 101, no. 34, 24 August 2004 (2004-08-24), pages 12682 - 7, XP002699746, DOI: doi:10.1073/pnas.0404875101
JUFANG SHAN ET AL.: "Identification of a Specific Inhibitor of the Dishevelled PDZ Domain", BIOCHEMISTRY, vol. 44, no. 47, 29 November 2005 (2005-11-29), pages 15495 - 503
TROSSET JY ET AL.: "Inhibition of protein-protein interactions: the discovery of druglike beta-catenin inhibitors by combining virtual and biophysical screening", PROTEINS, vol. 64, no. 1, 1 July 2006 (2006-07-01), pages 60 - 7, XP055186061, DOI: doi:10.1002/prot.20955
BERGE, BIGHLEY; MONKHOUSE, J. PHARM. SCI., vol. 66, 1977, pages 1 - 19
J. HONIG ET AL.: "The Van Nostrand Chemist's Dictionary", 1953, pages: 650
T. HIGUCHI; V. STELLA: "A.C.S. Symposium Series", vol. 14, article "Pro-Drugs as Novel Delivery Systems"
"Chemistry And Drug Discovery", vol. 1, article "Principles and Practice"
DRUG DISCOV. TODAY, vol. 10, 2005, pages 1467 - 1474
TETRAHEDRON, vol. 63, 2007, pages 12912 - 12916
AMERICAN JOURNAL OF TRANSPLANTATION, vol. 6, 2006, pages 50 - 59
NATURE MEDICINE, vol. 13, no. 7, 2007, pages 880 - 885
See also references of EP 2698365A4
Attorney, Agent or Firm:
SK INTELLECTUAL PROPERTY LAW FIRM et al. (JP)
SK patent business corporation (JP)
SK patent business corporation (JP)
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