Title:
CANCER THERAPEUTIC AGENT COMPRISING LIGAND FOR NEUROMEDIN U RECEPTOR 2 (FM4) MOLECULE AS ACTIVE INGREDIENT
Document Type and Number:
WIPO Patent Application WO/2008/029601
Kind Code:
A1
Abstract:
It is found that a neuromedin U receptor 2 (FM4) molecule is expressed at a high level in a cancer cell such as a pancreatic cancer cell. When a ligand for the molecule is examined on its cancer cell proliferation inhibition effect, it is found that the ligand can inhibit the proliferation of a cancer cell. It is also found that the effect can be produced by a signal via an FM4 molecule. These findings reveal that a ligand for a neuromedin U receptor 2 (FM4) molecule is effective for the treatment of or prevention of the metastasis of cancer having enhanced expression of the neuromedin U receptor 2 (FM4) molecule such as pancreatic cancer.
Inventors:
KIMURA NAOKI (JP)
Application Number:
PCT/JP2007/065904
Publication Date:
March 13, 2008
Filing Date:
August 15, 2007
Export Citation:
Assignee:
FORERUNNER PHARMA RES CO LTD (JP)
KIMURA NAOKI (JP)
KIMURA NAOKI (JP)
International Classes:
A61K45/00; A61K38/00; A61P35/00; A61P35/04; G01N33/15; G01N33/50; G01N33/53; G01N33/574
Domestic Patent References:
| WO2006024283A2 | 2006-03-09 |
Foreign References:
| JP2757348B2 | 1998-05-25 |
Other References:
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BRIGHTON ET AL.: "Neuromedin U and its receptors: Structure, Function and Physiological Roles", PHARMACOLOGICAL REVIEWS, vol. 56, 2004, pages 231 - 248, XP003002000
HOWARD ET AL.: "Identification of receptors for neuromedin U and its role in feeding", NATURE, vol. 406, 2000, pages 70 - 74, XP000926239
N. MINAMINO; K. KANGAWA; H. MATSUO.: "Neuromedin U-8 and U-25: Novel uterus stimulating and hypertensive peptides identified in porcine spinal cord", BIOCHEM. BIOPHYS. RES. COMMUN., vol. 130, 1985, pages 1078 - 1085, XP024848212, DOI: doi:10.1016/0006-291X(85)91726-7
M. KOJIMA ET AL.: "Purification and Identification of Neuromedin U as an Endogenous Ligand for an Orphan Receptor GPR66 (FM3", BIOCHEM. BIOPHYS. RES. COMMUN., vol. 276, 2000, pages 435 - 438, XP002944467, DOI: doi:10.1006/bbrc.2000.3502
HOWARD AD ET AL.: "Identification of receptors for neuromedin U and its role in feeding", NATURE, vol. 406, 2000, pages 70 - 74, XP000926239, DOI: doi:10.1038/35017610
SZEKERES PG ET AL.: "Neuromedin U is a potent agonist at the orphan G protein-coupled receptor FM3", J BIOL CHEM, vol. 275, 2000, pages 20247 - 20250, XP002163225, DOI: doi:10.1074/jbc.C000244200
R. FUJII ET AL.: "Identification of neuromedin U as the cognate ligand of the orphan G protein-coupled receptor FM-3", J. BIOL. CHEM., vol. 275, 2000, pages 21068 - 21074, XP002947592, DOI: doi:10.1074/jbc.M001546200
HOSOYA M ET AL.: "Identification and functional characterization of a novel subtype of neuromedin U receptor", J BIOL CHEM, vol. 275, 2000, pages 29528 - 29532, XP002942025, DOI: doi:10.1074/jbc.M004261200
RADDATZ R ET AL.: "Identification and characterization of two neuromedin U receptors differentially expressed in peripheral tissues and the central nervous system", J BIOL CHEM, vol. 275, 2000, pages 32452 - 32459, XP002944468, DOI: doi:10.1074/jbc.M004613200
HANADA R ET AL.: "Neuromedin U has a novel anorexigenic effect independent of the leptin signaling pathwa", NAT MED., vol. 10, 2004, pages 1067 - 73, XP009088830, DOI: doi:10.1038/nm1106
PAUL J. BRIGHTON; PHILIP G. SZEKERES; GARY B. WILLARS.: "Neuromedin U and Its Receptors: Structure", FUNCTION, AND PHYSIOLOGICAL ROLES. PHARMACOL REV, vol. 56, 2004, pages 231 - 248
SHETZLINE SE ET AL.: "Neuromedin U: A Myb-regulated autocrine growth factor for human myeloid leukemias", BLOOD., vol. 104, 2004, pages 1833 - 40
HASHIMOTO-GOTOH, T ET AL.: "An oligodeoxyribonucleotide-directed dual amber method for site-directed mutagenesis", GENE, vol. 152, 1995, pages 271 - 275
ZOLLER, MJ; SMITH, M.: "Oligonucleotide-directed mutagenesis of DNA fragments cloned into M13 vectors", METHODS ENZYMOL., vol. 100, 1983, pages 468 - 500, XP001088749, DOI: doi:10.1016/0076-6879(83)00074-9
KRAMER, W. ET AL.: "The gapped duplex DNA approach to oligonucleotide-directed mutation construction", NUCLEIC ACIDS RES., vol. 12, 1984, pages 9441 - 9456, XP002026371
KRAMER W; FRITZ HJ: "Oligonucleotide-directed construction of mutations via gapped duplex", DNA METHODS. ENZYMOL., vol. 154, 1987, pages 350 - 367
KUNKEL, TA: "Rapid and efficient site-specific mutagenesis without phenotypic selection", PROC. NATL. ACAD. SCI. USA., vol. 82, 1985, pages 488 - 492
MARK, D. F. ET AL., PROC. NATL. ACAD. SCI. USA, vol. 81, 1984, pages 5662 - 5666
ZOLLER, M. J.; SMITH, M., NUCLEIC ACIDS RESEARCH, vol. 10, 1982, pages 6487 - 500
SCIENCE, vol. 224, 1984, pages 1431 - 3
DALBADIE-MCFARLAND, G. ET AL., PROC. NATL. ACAD. SCI. USA, vol. 79, 1982, pages 6409 - 6413
KARLIN; ALTSCHUL, PROC. NATL. ACAD. SCI. USA, vol. 90, 1993, pages 5873 - 7
CHIRGWIN, J. M. ET AL., BIOCHEMISTRY, vol. 18, 1979, pages 5294 - 5299
CHOMCZYNSKI, P.; SACCHI, N., ANAL. BIOCHEM., vol. 162, 1987, pages 156 - 159
FROHMAN, M. A. ET AL., PROC. NATL. ACAD. SCI. U.S.A., vol. 85, 1988, pages 8998 - 9002
BELYAVSKY, A. ET AL., NUCLEIC ACIDS RES., vol. 17, 1989, pages 2919 - 2932
J. SAMBROOK ET AL.: "Molecular Cloning", 1989, COLD SPRING HARBOR LAB. PRESS
"PCR Protocols, A Guide to Methods and Applications", 1990, ACADEMIC PRESS
"Cell and Molecular Biology, In-Situ PCR Techniques", 1997
PROC. NATL. ACAD. SCI. USA, vol. 60, 1996, pages 160
J. MOL. BIOL., vol. 41, 1969, pages 459
GENETICS, vol. 39, 1954, pages 4401
GENE, vol. 24, 1983, pages 255
VAUGHN J. L. ET AL., IN VIVO, vol. 13, 1977, pages 213 - 217
J. EXP. MED., vol. 108, 1995, pages 945
PROC. NATL. ACAD. SCI. USA, vol. 77, 1980, pages 4216 - 4220
VALLE ET AL., NATURE, vol. 291, 1981, pages 338 - 340
ZOLLER, M. J.; SMITH, M., NUCLEIC ACIDS RESEARCH, vol. 10, 1982, pages 6487 - 6500
WANG, A. ET AL., SCIENCE, vol. 224, pages 1431 - 1433
ALTSCHUL, NUCLEIC ACIDS RES., vol. 25, 1997, pages 3389 - 3402
ALTSCHUL, J. MOL. BIOL., vol. 215, 1990, pages 403 - 410
SMITH, J. MOL. BIOL., vol. 147, 1981, pages 195 - 197
BIOCHEM., vol. 179, 1989, pages 1 - 7
J. IMMUNOL. METHODS, vol. 65, 1983, pages 55 - 63
CANCER COMMUN., vol. 3, 1991, pages 207 - 212
CANCER RES., vol. 48, 1988, pages 4827 - 4833
See also references of EP 2052739A4
BRIGHTON ET AL.: "Neuromedin U and its receptors: Structure, Function and Physiological Roles", PHARMACOLOGICAL REVIEWS, vol. 56, 2004, pages 231 - 248, XP003002000
HOWARD ET AL.: "Identification of receptors for neuromedin U and its role in feeding", NATURE, vol. 406, 2000, pages 70 - 74, XP000926239
N. MINAMINO; K. KANGAWA; H. MATSUO.: "Neuromedin U-8 and U-25: Novel uterus stimulating and hypertensive peptides identified in porcine spinal cord", BIOCHEM. BIOPHYS. RES. COMMUN., vol. 130, 1985, pages 1078 - 1085, XP024848212, DOI: doi:10.1016/0006-291X(85)91726-7
M. KOJIMA ET AL.: "Purification and Identification of Neuromedin U as an Endogenous Ligand for an Orphan Receptor GPR66 (FM3", BIOCHEM. BIOPHYS. RES. COMMUN., vol. 276, 2000, pages 435 - 438, XP002944467, DOI: doi:10.1006/bbrc.2000.3502
HOWARD AD ET AL.: "Identification of receptors for neuromedin U and its role in feeding", NATURE, vol. 406, 2000, pages 70 - 74, XP000926239, DOI: doi:10.1038/35017610
SZEKERES PG ET AL.: "Neuromedin U is a potent agonist at the orphan G protein-coupled receptor FM3", J BIOL CHEM, vol. 275, 2000, pages 20247 - 20250, XP002163225, DOI: doi:10.1074/jbc.C000244200
R. FUJII ET AL.: "Identification of neuromedin U as the cognate ligand of the orphan G protein-coupled receptor FM-3", J. BIOL. CHEM., vol. 275, 2000, pages 21068 - 21074, XP002947592, DOI: doi:10.1074/jbc.M001546200
HOSOYA M ET AL.: "Identification and functional characterization of a novel subtype of neuromedin U receptor", J BIOL CHEM, vol. 275, 2000, pages 29528 - 29532, XP002942025, DOI: doi:10.1074/jbc.M004261200
RADDATZ R ET AL.: "Identification and characterization of two neuromedin U receptors differentially expressed in peripheral tissues and the central nervous system", J BIOL CHEM, vol. 275, 2000, pages 32452 - 32459, XP002944468, DOI: doi:10.1074/jbc.M004613200
HANADA R ET AL.: "Neuromedin U has a novel anorexigenic effect independent of the leptin signaling pathwa", NAT MED., vol. 10, 2004, pages 1067 - 73, XP009088830, DOI: doi:10.1038/nm1106
PAUL J. BRIGHTON; PHILIP G. SZEKERES; GARY B. WILLARS.: "Neuromedin U and Its Receptors: Structure", FUNCTION, AND PHYSIOLOGICAL ROLES. PHARMACOL REV, vol. 56, 2004, pages 231 - 248
SHETZLINE SE ET AL.: "Neuromedin U: A Myb-regulated autocrine growth factor for human myeloid leukemias", BLOOD., vol. 104, 2004, pages 1833 - 40
HASHIMOTO-GOTOH, T ET AL.: "An oligodeoxyribonucleotide-directed dual amber method for site-directed mutagenesis", GENE, vol. 152, 1995, pages 271 - 275
ZOLLER, MJ; SMITH, M.: "Oligonucleotide-directed mutagenesis of DNA fragments cloned into M13 vectors", METHODS ENZYMOL., vol. 100, 1983, pages 468 - 500, XP001088749, DOI: doi:10.1016/0076-6879(83)00074-9
KRAMER, W. ET AL.: "The gapped duplex DNA approach to oligonucleotide-directed mutation construction", NUCLEIC ACIDS RES., vol. 12, 1984, pages 9441 - 9456, XP002026371
KRAMER W; FRITZ HJ: "Oligonucleotide-directed construction of mutations via gapped duplex", DNA METHODS. ENZYMOL., vol. 154, 1987, pages 350 - 367
KUNKEL, TA: "Rapid and efficient site-specific mutagenesis without phenotypic selection", PROC. NATL. ACAD. SCI. USA., vol. 82, 1985, pages 488 - 492
MARK, D. F. ET AL., PROC. NATL. ACAD. SCI. USA, vol. 81, 1984, pages 5662 - 5666
ZOLLER, M. J.; SMITH, M., NUCLEIC ACIDS RESEARCH, vol. 10, 1982, pages 6487 - 500
SCIENCE, vol. 224, 1984, pages 1431 - 3
DALBADIE-MCFARLAND, G. ET AL., PROC. NATL. ACAD. SCI. USA, vol. 79, 1982, pages 6409 - 6413
KARLIN; ALTSCHUL, PROC. NATL. ACAD. SCI. USA, vol. 90, 1993, pages 5873 - 7
CHIRGWIN, J. M. ET AL., BIOCHEMISTRY, vol. 18, 1979, pages 5294 - 5299
CHOMCZYNSKI, P.; SACCHI, N., ANAL. BIOCHEM., vol. 162, 1987, pages 156 - 159
FROHMAN, M. A. ET AL., PROC. NATL. ACAD. SCI. U.S.A., vol. 85, 1988, pages 8998 - 9002
BELYAVSKY, A. ET AL., NUCLEIC ACIDS RES., vol. 17, 1989, pages 2919 - 2932
J. SAMBROOK ET AL.: "Molecular Cloning", 1989, COLD SPRING HARBOR LAB. PRESS
"PCR Protocols, A Guide to Methods and Applications", 1990, ACADEMIC PRESS
"Cell and Molecular Biology, In-Situ PCR Techniques", 1997
PROC. NATL. ACAD. SCI. USA, vol. 60, 1996, pages 160
J. MOL. BIOL., vol. 41, 1969, pages 459
GENETICS, vol. 39, 1954, pages 4401
GENE, vol. 24, 1983, pages 255
VAUGHN J. L. ET AL., IN VIVO, vol. 13, 1977, pages 213 - 217
J. EXP. MED., vol. 108, 1995, pages 945
PROC. NATL. ACAD. SCI. USA, vol. 77, 1980, pages 4216 - 4220
VALLE ET AL., NATURE, vol. 291, 1981, pages 338 - 340
ZOLLER, M. J.; SMITH, M., NUCLEIC ACIDS RESEARCH, vol. 10, 1982, pages 6487 - 6500
WANG, A. ET AL., SCIENCE, vol. 224, pages 1431 - 1433
ALTSCHUL, NUCLEIC ACIDS RES., vol. 25, 1997, pages 3389 - 3402
ALTSCHUL, J. MOL. BIOL., vol. 215, 1990, pages 403 - 410
SMITH, J. MOL. BIOL., vol. 147, 1981, pages 195 - 197
BIOCHEM., vol. 179, 1989, pages 1 - 7
J. IMMUNOL. METHODS, vol. 65, 1983, pages 55 - 63
CANCER COMMUN., vol. 3, 1991, pages 207 - 212
CANCER RES., vol. 48, 1988, pages 4827 - 4833
See also references of EP 2052739A4
Attorney, Agent or Firm:
SHIMIZU, Hatsushi et al. (1-1-1 Oroshi-mach, Tsuchiura-shi Ibaraki 47, JP)
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