Title:
AMELIORATING AGENT FOR OBESITY-RELATED METABOLIC DISEASE
Document Type and Number:
WIPO Patent Application WO/2020/050290
Kind Code:
A1
Abstract:
The purpose of the present invention is to provide a medicine which contains a small-molecule compound as an active ingredient, and which can exhibit an activity to ameliorate an obesity-related metabolic disease, e.g., an anti-obesity activity, without decreasing the amount of food intake upon the binding to Helz2 to decrease the activity of Helz2, wherein Helz2 is a substance which can be expressed strongly in the liver in both of a human and a mouse and of which the expression amount significantly increases in the liver of a human suffering from NAFLD that is an obesity-related metabolic disease and the fatty liver of a mouse suffering from obesity. The present invention provides: an ameliorating agent for an obesity-related metabolic disease, particularly an ameliorating agent for fatty liver, characterized by containing guanabenz or a salt thereof as an active ingredient.
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Inventors:
MORI MASATOMO (JP)
Application Number:
PCT/JP2019/034675
Publication Date:
March 12, 2020
Filing Date:
September 03, 2019
Export Citation:
Assignee:
METABOLIC AND OBESE RES SCIENCE CORPORATION (JP)
International Classes:
A61K31/155; A61P1/16; A61P3/00; A61P3/04; A61P3/06; A61P3/10; A61P5/50; A61P9/00; A61P9/10; A61P9/12; A61P13/12; A61P19/06; A61P43/00
Other References:
IGAKI, NAOYA ET AL.: "The effect of guanabenz acetate on glycation", JOURNAL OF THE JAPAN DIABETES SOCIETY, vol. 33, no. 5, 30 May 1990 (1990-05-30), pages 421 - 424, XP055799245
CAPUZZI DAVID M., CEVALLOS WILLIAM H.: "Inhibition of hepatic cholesterol and triglyceride synthesis by guanabenz acetate", J. CARDIOVASC. PHARMACOL., vol. 6, 1984, pages S847 - 852, XP009527210, DOI: 10.1097/00005344-198400065-00024
MCCARRON, D. A.: "Step-one antihypertensive therapy: a comparison of a centrally acting agent and a diuretic", J. CARDIOVASC. PHARMACOL., vol. 6, no. 5, 1984, pages 853 - 858, XP055799248
"Guidelines for the management of obesity disease 2016", 2016, LIFE SCIENCE PUBLISHING CO., LTD.
"Regulation of hepatic glucose metabolism in health and disease", NATURE REV ENDOCRINOL, vol. 13, 2017, pages 572 - 587
"Hepatokine: linking nonalcoholic fatty liver disorder and insulin resistance", NATURE REV ENDOCRINOL, vol. 13, 2017, pages 509 - 520
"Selective versus total insulin resistance: a pathogenic paradox", CELL METAB, vol. 7, 2008, pages 95 - 96
"Mechanisms of NAFLD development and therapeutic strategies", NATURE MEDICINE, vol. 24, 2018, pages 908 - 922
"Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis", GASTROENTEROLOGY, vol. 149, 2015, pages 367 - 378
"Isolation and characterization of a transcriptional cofactor and its novel isoform that binds the deoxyribonucleic acid-binding domain of peroxisome proliferator-activated receptor-y", ENDOCRINOLOGY, vol. 147, 2006, pages 377 - 388
"Protection against high-fat diet-induce obesity in Helz2-defiecient male mice due to enhanced expression of hepatic leptin receptor", ENDOCRINOLOGY, vol. 155, 2014, pages 3459 - 3472
BRIT JNUTR, vol. 101, 2009, pages 701 - 708
BRIT J NUTR, vol. 101, 2009, pages 701 - 708
MATSUSUE K ET AL., J CLIN INVEST, vol. 111, 2003, pages 737
"General Rules for Preparation in The Japanese Pharmacopoeia"
CAPUZZI DAVID M., CEVALLOS WILLIAM H.: "Inhibition of hepatic cholesterol and triglyceride synthesis by guanabenz acetate", J. CARDIOVASC. PHARMACOL., vol. 6, 1984, pages S847 - 852, XP009527210, DOI: 10.1097/00005344-198400065-00024
MCCARRON, D. A.: "Step-one antihypertensive therapy: a comparison of a centrally acting agent and a diuretic", J. CARDIOVASC. PHARMACOL., vol. 6, no. 5, 1984, pages 853 - 858, XP055799248
"Guidelines for the management of obesity disease 2016", 2016, LIFE SCIENCE PUBLISHING CO., LTD.
"Regulation of hepatic glucose metabolism in health and disease", NATURE REV ENDOCRINOL, vol. 13, 2017, pages 572 - 587
"Hepatokine: linking nonalcoholic fatty liver disorder and insulin resistance", NATURE REV ENDOCRINOL, vol. 13, 2017, pages 509 - 520
"Selective versus total insulin resistance: a pathogenic paradox", CELL METAB, vol. 7, 2008, pages 95 - 96
"Mechanisms of NAFLD development and therapeutic strategies", NATURE MEDICINE, vol. 24, 2018, pages 908 - 922
"Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis", GASTROENTEROLOGY, vol. 149, 2015, pages 367 - 378
"Isolation and characterization of a transcriptional cofactor and its novel isoform that binds the deoxyribonucleic acid-binding domain of peroxisome proliferator-activated receptor-y", ENDOCRINOLOGY, vol. 147, 2006, pages 377 - 388
"Protection against high-fat diet-induce obesity in Helz2-defiecient male mice due to enhanced expression of hepatic leptin receptor", ENDOCRINOLOGY, vol. 155, 2014, pages 3459 - 3472
BRIT JNUTR, vol. 101, 2009, pages 701 - 708
BRIT J NUTR, vol. 101, 2009, pages 701 - 708
MATSUSUE K ET AL., J CLIN INVEST, vol. 111, 2003, pages 737
"General Rules for Preparation in The Japanese Pharmacopoeia"
Attorney, Agent or Firm:
INABA, Yoshiyuki et al. (JP)
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