Title:
COMPOSITION FOR TREATING OR PREVENTING OBESITY OR OBESITY-ASSOCIATED LIVER DISEASE, COMPRISING VERBENONE DERIVATIVES
Document Type and Number:
WIPO Patent Application WO/2023/033517
Kind Code:
A1
Abstract:
The present invention relates to a pharmaceutical composition or a health functional food for treating or preventing obesity or obesity-associated liver disease, containing verbenone derivatives and pharmaceutically acceptable salts thereof as active ingredients. Specifically, the verbenone derivatives of the present invention inhibit TGF-β/Smad3 signaling in a high-fat diet-induced mouse and thus may treat and prevent obesity or obesity-associated liver disease.
Inventors:
JU CHUNG (KR)
LEE DONG WON (KR)
LEE SEUNG KYU (KR)
CHUNG SUNG (KR)
LEE DONG WON (KR)
LEE SEUNG KYU (KR)
CHUNG SUNG (KR)
Application Number:
PCT/KR2022/012956
Publication Date:
March 09, 2023
Filing Date:
August 30, 2022
Export Citation:
Assignee:
SHIN POONG PHARMACEUTICAL CO LTD (KR)
International Classes:
A61K31/122; A61P1/16; A61P3/04
Domestic Patent References:
| WO2016122288A2 | 2016-08-04 | |||
| WO2020055129A1 | 2020-03-19 |
Foreign References:
| KR20140031568A | 2014-03-13 | |||
| KR20190000026A | 2019-01-02 |
Other References:
PAHK KISOO, NOH HYOJIN, JOUNG CHANMIN, JANG MI, SONG HWA YOUNG, KIM KYUNG WON, HAN KIHOON, HWANG JONG-IK, KIM SUNGEUN, KIM WON-KI: "A novel CD147 inhibitor, SP-8356, reduces neointimal hyperplasia and arterial stiffness in a rat model of partial carotid artery ligation", JOURNAL OF TRANSLATIONAL MEDICINE, vol. 17, no. 1, 1 December 2019 (2019-12-01), XP055859550, DOI: 10.1186/s12967-019-2024-y
LOU JIAXIN; LI CAN; LI ZENG-SHAN; ZHANG TIAN; CHEN ZHI-NAN; BIAN HUIJIE: "Hepatic CD147 knockout modulates liver steatosis and up-regulates autophagy in high-fat-diet-induced NAFLD mice", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, ELSEVIER, AMSTERDAM NL, vol. 524, no. 4, 13 February 2020 (2020-02-13), Amsterdam NL , pages 1010 - 1017, XP086092527, ISSN: 0006-291X, DOI: 10.1016/j.bbrc.2020.01.164
PAHK KISOO; LEE SANG GIL; JOUNG CHANMIN; KIM EUN-OK; KWON HYUN WOO; KIM DONG HWI; HWANG JONG-IK; KIM SUNGEUN; KIM WON-KI: "SP-1154, a novel synthetic TGF-β inhibitor, alleviates obesity and hepatic steatosis in high-fat diet-induced mice", BIOMEDICINE & PHARMACOTHERAPY, ELSEVIER, FR, vol. 145, 20 November 2021 (2021-11-20), FR , XP086898275, ISSN: 0753-3322, DOI: 10.1016/j.biopha.2021.112441
BYRNE CDTARGHER G.: "NAFLD: a multisystem disease", JOURNAL OF HEPATOLOGY, vol. 62, 2015, pages S47 - S64, XP055680969, DOI: 10.1016/j.jhep.2014.12.012
YOUNOSSI ZMBLISSETT DBLISSETT RHENRY LSTEPANOVA MYOUNOSSI Y ET AL.: "The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe", HEPATOLOGY, vol. 64, 2016, pages 1577 - 86, XP071562122, DOI: 10.1002/hep.28785
YOUNOSSI ZMKOENIG ABABDELATIF DFAZEL YHENRY LWYMER M: "Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes", HEPATOLOGY, vol. 64, 2016, pages 73 - 84
KHAN RSBRIL FCUSI KNEWSOME PN: "Modulation of insulin resistance in nonalcoholic fatty liver disease", HEPATOLOGY, vol. 70, 2019, pages 711 - 24, XP071565876, DOI: 10.1002/hep.30429
AZZU VVACCA MVIRTUE SALLISON MVIDAL-PUIG A: "Adipose tissue-liver cross talk in the control of whole-body metabolism: implications in non-alcoholic fatty liver disease", GASTROENTEROLOGY, 2020
FRIEDMAN SLNEUSCHWANDER-TETRI BARINELLA MSANYAL AJ: "Mechanisms of NAFLD development and therapeutic strategies", NATURE MEDICINE, vol. 24, 2018, pages 908 - 22, XP036542053, DOI: 10.1038/s41591-018-0104-9
WANG YTANG BLONG LLUO PXIANG WLI X ET AL.: "Improvement of obesity-associated disorders by a small-molecule drug targeting mitochondria of adipose tissue macrophages", NATURE COMMUNICATIONS., vol. 12, 2021, pages 1 - 16
LEE M-J.: "Transforming growth factor beta superfamily regulation of adipose tissue biology in obesity", BIOCHIMICA ET BIOPHYSICA ACTA (BBA)-MOLECULAR BASIS OF DISEASE., vol. 1864, 2018, pages 1160 - 71
SOUSA-PINTO BGONCALVES LRODRIGUES ARTADA IALMEIDA HNEVES D ET AL.: "Characterization of TGF-β expression and signaling profile in the adipose tissue of rats fed with high-fat and energy-restricted diets", THE JOURNAL OF NUTRITIONAL BIOCHEMISTRY, vol. 38, 2016, pages 107 - 15, XP029795114, DOI: 10.1016/j.jnutbio.2016.07.017
TAN CCHONG HTAN ETAN N: "Getting 'Smad' about obesity and diabetes", NUTRITION & DIABETES, vol. 2, 2012, pages e29
TAN CKLEUENBERGER NTAN MJYAN YWCHEN YKAMBADUR R ET AL.: "Smad3 deficiency in mice protects against insulin resistance and obesity induced by a high-fat diet", DIABETES, vol. 60, 2011, pages 464 - 76, XP055489525, DOI: 10.2337/db10-0801
YADAV HQUIJANO CKAMARAJU AKGAVRILOVA OMALEK RCHEN W ET AL.: "Protection from obesity and diabetes by blockade of TGF-P/Smad3 signaling", CELL METABOLISM., vol. 14, 2011, pages 67 - 79, XP028239684, DOI: 10.1016/j.cmet.2011.04.013
JU CSONG SHWANG SKIM CKIM MGU J ET AL.: "Discovery of novel (1 S)-(-)-verbenone derivatives with anti-oxidant and anti-ischemic effects", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 23, 2013, pages 5421 - 5, XP028707922, DOI: 10.1016/j.bmcl.2013.07.038
NGUYEN HTREYES-ALCARAZ AYONG HJNGUYEN LPPARK H-KINOUE A ET AL.: "CXCR7: a (3-arrestin-biased receptor that potentiates cell migration and recruits P-arrestin2 exclusively through G0 subunits and GRK2", CELL & BIOSCIENCE, vol. 10, 2020, pages 1 - 19
BACHMANOV AAREED DRBEAUCHAMP GKTORDOFF MG: "Food intake, water intake, and drinking spout side preference of 28 mouse strains", BEHAVIOR GENETICS., vol. 32, 2002, pages 435 - 43
PAHK KKIM EJJOUNG CSEO HSKIM S: "Exercise training reduces inflammatory metabolic activity of visceral fat assessed by 18F-FDG PET/CT in obese women", CLINICAL ENDOCRINOLOGY, 2020
PAHK KKIM EJJOUNG CSEO HSKIM S: "Association of glucose uptake of visceral fat and acute myocardial infarction: a pilot 18 F-FDG PET/CT study", CARDIOVASCULAR DIABETOLOGY., vol. 19, 2020, pages 1 - 11
JIMENEZ-GOMEZ YMATTISON JAPEARSON KJMARTIN-MONTALVO APALACIOS HHSOSSONG AM ET AL.: "Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on high-fat, high-sugar diet", CELL METABOLISM., vol. 18, 2013, pages 533 - 45
LEE ESKWON M-HKIM HMWOO HBAHN CMCHUNG CH: "Curcumin analog CUR5-8 ameliorates nonalcoholic fatty liver disease in mice with high-fat diet-induced obesity", METABOLISM, vol. 103, 2020, pages 154015
LIVAK KJSCHMITTGEN TD, ANALYSIS OF RELATIVE GENE EXPRESSION DATA USING REAL-TIME QUANTITATIVE PCR AND THE 2- ΔΔCT METHOD, METHODS, vol. 25, 2001, pages 402 - 8
ELSEGOOD CLCHANG MJESSUP WSCHOLZ GMHAMILTON JA.: "Glucose Metabolism Is Required for Oxidized LDL-Induced Macrophage Survival: Role of PI3K and Bcl-2 Family Proteins", ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY, vol. 29, 2009, pages 1283 - 9
MORAES-VIEIRA PMSAGHATELIAN AKAHN BB: "GLUT4 expression in adipocytes regulates de novo lipogenesis and levels of a novel class of lipids with antidiabetic and anti-inflammatory effects", DIABETES, vol. 65, 2016, pages 1808 - 15
VIGLINO DMARTIN MALMERAS NDESPRES J-PCOXSON HOPEPIN J-L ET AL.: "Low Liver Density Is Linked to Cardiovascular Comorbidity in COPD: An ECLIPSE Cohort Analysis", INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE, vol. 14, 2019, pages 3053
UM MYMOON MKAHN JHA TY: "Coumarin attenuates hepatic steatosis by down-regulating lipogenic gene expression in mice fed a high-fat diet", BRITISH JOURNAL OF NUTRITION, vol. 109, 2013, pages 1590 - 7
FENG DZOU JSU DMAI HZHANG SLI P ET AL.: "Curcumin prevents high-fat diet-induced hepatic steatosis in ApoE-/- mice by improving intestinal barrier function and reducing endotoxin and liver TLR4/NF- B inflammation", NUTRITION & METABOLISM., vol. 16, 2019, pages 1 - 11
CILDIR GAKINCILAR SCTERGAONKAR V: "Chronic adipose tissue inflammation: all immune cells on the stage", TRENDS IN MOLECULAR MEDICINE., vol. 19, 2013, pages 487 - 500
XIE LORTEGA MTMORA SCHAPES SK: "Interactive changes between macrophages and adipocytes", CLINICAL AND VACCINE IMMUNOLOGY., vol. 17, 2010, pages 651 - 9, XP055766767, DOI: 10.1128/CVI.00494-09
LUMENG CNDEYOUNG SMSALTIEL AR: "Macrophages block insulin action in adipocytes by altering expression of signaling and glucose transport proteins", AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, vol. 292, 2007, pages E166 - E74
CHALASANI NYOUNOSSI ZLAVINE JECHARLTON MCUSI KRINELLA M ET AL.: "The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases", HEPATOLOGY, vol. 67, 2018, pages 328 - 57, XP055632257, DOI: 10.1002/hep.29367
ADAMS LALYMP JFSAUVER JSSANDERSON SOLINDOR KDFELDSTEIN A ET AL.: "The natural history of nonalcoholic fatty liver disease: a population-based cohort study", GASTROENTEROLOGY, vol. 129, 2005, pages 113 - 21, XP005313832, DOI: 10.1053/j.gastro.2005.04.014
MUSOLINO VGLIOZZI MSCARANO FBOSCO FSCICCHITANO MNUCERA S ET AL.: "Bergamot polyphenols improve dyslipidemia and pathophysiological features in a mouse model of non-alcoholic fatty liver disease", SCIENTIFIC REPORTS., vol. 10, 2020, pages 1 - 14
NAM J-STERABE MMAMURA MKANG M-JCHAE HSTUELTEN C ET AL.: "An anti-transforming growth factor 0 antibody suppresses metastasis via cooperative effects on multiple cell compartments", CANCER RESEARCH, vol. 68, 2008, pages 3835 - 43
TAKAHASHI KAKATSU YPODYMA-INOUE KAMATSUMOTO TTAKAHASHI HYOSHIMATSU Y ET AL.: "Targeting all transforming growth factor-(3 isoforms with an Fc chimeric receptor impairs tumor growth and angiogenesis of oral squamous cell cancer", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 295, 2020, pages 12559 - 72, XP055729675, DOI: 10.1074/jbc.RA120.012492
CHAMES PVAN REGENMORTEL MWEISS EBATY D: "Therapeutic antibodies: successes, limitations and hopes for the future", BRITISH JOURNAL OF PHARMACOLOGY., vol. 157, 2009, pages 220 - 33, XP002714017, DOI: 10.1111/j.1476-5381.2009.00190.x
BELL MRENGLEKA MJMALIK ASTRICKLER JE: "To fuse or not to fuse: what is your purpose?", PROTEIN SCIENCE, vol. 22, 2013, pages 1466 - 77, XP055692508, DOI: 10.1002/pro.2356
SANTIAGO BGUTIERREZ-CANAS IDOTOR JPALAO GLASARTE JJRUIZ J ET AL.: "Topical application of a peptide inhibitor of transforming growth factor-(31 ameliorates bleomycin-induced skin fibrosis", JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 125, 2005, pages 450 - 5, XP002604583
GALLO-OLLER GVOLLMANN-ZWERENZ AMELENDEZ BREY JAHAU PDOTOR J ET AL.: "P144, a Transforming Growth Factor beta inhibitor peptide, generates antitumoral effects and modifies SMAD7 and SKI levels in human glioblastoma cell lines", CANCER LETTERS, vol. 381, 2016, pages 67 - 75, XP029715488, DOI: 10.1016/j.canlet.2016.07.029
HUANG C-YCHUNG C-LHU T-HCHEN J-JLIU P-FCHEN C-L: "Recent progress in TGF-β inhibitors for cancer therapy", BIOMEDICINE & PHARMACOTHERAPY., vol. 134, 2021, pages 111046
LOU JIAXIN; LI CAN; LI ZENG-SHAN; ZHANG TIAN; CHEN ZHI-NAN; BIAN HUIJIE: "Hepatic CD147 knockout modulates liver steatosis and up-regulates autophagy in high-fat-diet-induced NAFLD mice", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, ELSEVIER, AMSTERDAM NL, vol. 524, no. 4, 13 February 2020 (2020-02-13), Amsterdam NL , pages 1010 - 1017, XP086092527, ISSN: 0006-291X, DOI: 10.1016/j.bbrc.2020.01.164
PAHK KISOO; LEE SANG GIL; JOUNG CHANMIN; KIM EUN-OK; KWON HYUN WOO; KIM DONG HWI; HWANG JONG-IK; KIM SUNGEUN; KIM WON-KI: "SP-1154, a novel synthetic TGF-β inhibitor, alleviates obesity and hepatic steatosis in high-fat diet-induced mice", BIOMEDICINE & PHARMACOTHERAPY, ELSEVIER, FR, vol. 145, 20 November 2021 (2021-11-20), FR , XP086898275, ISSN: 0753-3322, DOI: 10.1016/j.biopha.2021.112441
BYRNE CDTARGHER G.: "NAFLD: a multisystem disease", JOURNAL OF HEPATOLOGY, vol. 62, 2015, pages S47 - S64, XP055680969, DOI: 10.1016/j.jhep.2014.12.012
YOUNOSSI ZMBLISSETT DBLISSETT RHENRY LSTEPANOVA MYOUNOSSI Y ET AL.: "The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe", HEPATOLOGY, vol. 64, 2016, pages 1577 - 86, XP071562122, DOI: 10.1002/hep.28785
YOUNOSSI ZMKOENIG ABABDELATIF DFAZEL YHENRY LWYMER M: "Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes", HEPATOLOGY, vol. 64, 2016, pages 73 - 84
KHAN RSBRIL FCUSI KNEWSOME PN: "Modulation of insulin resistance in nonalcoholic fatty liver disease", HEPATOLOGY, vol. 70, 2019, pages 711 - 24, XP071565876, DOI: 10.1002/hep.30429
AZZU VVACCA MVIRTUE SALLISON MVIDAL-PUIG A: "Adipose tissue-liver cross talk in the control of whole-body metabolism: implications in non-alcoholic fatty liver disease", GASTROENTEROLOGY, 2020
FRIEDMAN SLNEUSCHWANDER-TETRI BARINELLA MSANYAL AJ: "Mechanisms of NAFLD development and therapeutic strategies", NATURE MEDICINE, vol. 24, 2018, pages 908 - 22, XP036542053, DOI: 10.1038/s41591-018-0104-9
WANG YTANG BLONG LLUO PXIANG WLI X ET AL.: "Improvement of obesity-associated disorders by a small-molecule drug targeting mitochondria of adipose tissue macrophages", NATURE COMMUNICATIONS., vol. 12, 2021, pages 1 - 16
LEE M-J.: "Transforming growth factor beta superfamily regulation of adipose tissue biology in obesity", BIOCHIMICA ET BIOPHYSICA ACTA (BBA)-MOLECULAR BASIS OF DISEASE., vol. 1864, 2018, pages 1160 - 71
SOUSA-PINTO BGONCALVES LRODRIGUES ARTADA IALMEIDA HNEVES D ET AL.: "Characterization of TGF-β expression and signaling profile in the adipose tissue of rats fed with high-fat and energy-restricted diets", THE JOURNAL OF NUTRITIONAL BIOCHEMISTRY, vol. 38, 2016, pages 107 - 15, XP029795114, DOI: 10.1016/j.jnutbio.2016.07.017
TAN CCHONG HTAN ETAN N: "Getting 'Smad' about obesity and diabetes", NUTRITION & DIABETES, vol. 2, 2012, pages e29
TAN CKLEUENBERGER NTAN MJYAN YWCHEN YKAMBADUR R ET AL.: "Smad3 deficiency in mice protects against insulin resistance and obesity induced by a high-fat diet", DIABETES, vol. 60, 2011, pages 464 - 76, XP055489525, DOI: 10.2337/db10-0801
YADAV HQUIJANO CKAMARAJU AKGAVRILOVA OMALEK RCHEN W ET AL.: "Protection from obesity and diabetes by blockade of TGF-P/Smad3 signaling", CELL METABOLISM., vol. 14, 2011, pages 67 - 79, XP028239684, DOI: 10.1016/j.cmet.2011.04.013
JU CSONG SHWANG SKIM CKIM MGU J ET AL.: "Discovery of novel (1 S)-(-)-verbenone derivatives with anti-oxidant and anti-ischemic effects", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 23, 2013, pages 5421 - 5, XP028707922, DOI: 10.1016/j.bmcl.2013.07.038
NGUYEN HTREYES-ALCARAZ AYONG HJNGUYEN LPPARK H-KINOUE A ET AL.: "CXCR7: a (3-arrestin-biased receptor that potentiates cell migration and recruits P-arrestin2 exclusively through G0 subunits and GRK2", CELL & BIOSCIENCE, vol. 10, 2020, pages 1 - 19
BACHMANOV AAREED DRBEAUCHAMP GKTORDOFF MG: "Food intake, water intake, and drinking spout side preference of 28 mouse strains", BEHAVIOR GENETICS., vol. 32, 2002, pages 435 - 43
PAHK KKIM EJJOUNG CSEO HSKIM S: "Exercise training reduces inflammatory metabolic activity of visceral fat assessed by 18F-FDG PET/CT in obese women", CLINICAL ENDOCRINOLOGY, 2020
PAHK KKIM EJJOUNG CSEO HSKIM S: "Association of glucose uptake of visceral fat and acute myocardial infarction: a pilot 18 F-FDG PET/CT study", CARDIOVASCULAR DIABETOLOGY., vol. 19, 2020, pages 1 - 11
JIMENEZ-GOMEZ YMATTISON JAPEARSON KJMARTIN-MONTALVO APALACIOS HHSOSSONG AM ET AL.: "Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on high-fat, high-sugar diet", CELL METABOLISM., vol. 18, 2013, pages 533 - 45
LEE ESKWON M-HKIM HMWOO HBAHN CMCHUNG CH: "Curcumin analog CUR5-8 ameliorates nonalcoholic fatty liver disease in mice with high-fat diet-induced obesity", METABOLISM, vol. 103, 2020, pages 154015
LIVAK KJSCHMITTGEN TD, ANALYSIS OF RELATIVE GENE EXPRESSION DATA USING REAL-TIME QUANTITATIVE PCR AND THE 2- ΔΔCT METHOD, METHODS, vol. 25, 2001, pages 402 - 8
ELSEGOOD CLCHANG MJESSUP WSCHOLZ GMHAMILTON JA.: "Glucose Metabolism Is Required for Oxidized LDL-Induced Macrophage Survival: Role of PI3K and Bcl-2 Family Proteins", ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY, vol. 29, 2009, pages 1283 - 9
MORAES-VIEIRA PMSAGHATELIAN AKAHN BB: "GLUT4 expression in adipocytes regulates de novo lipogenesis and levels of a novel class of lipids with antidiabetic and anti-inflammatory effects", DIABETES, vol. 65, 2016, pages 1808 - 15
VIGLINO DMARTIN MALMERAS NDESPRES J-PCOXSON HOPEPIN J-L ET AL.: "Low Liver Density Is Linked to Cardiovascular Comorbidity in COPD: An ECLIPSE Cohort Analysis", INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE, vol. 14, 2019, pages 3053
UM MYMOON MKAHN JHA TY: "Coumarin attenuates hepatic steatosis by down-regulating lipogenic gene expression in mice fed a high-fat diet", BRITISH JOURNAL OF NUTRITION, vol. 109, 2013, pages 1590 - 7
FENG DZOU JSU DMAI HZHANG SLI P ET AL.: "Curcumin prevents high-fat diet-induced hepatic steatosis in ApoE-/- mice by improving intestinal barrier function and reducing endotoxin and liver TLR4/NF- B inflammation", NUTRITION & METABOLISM., vol. 16, 2019, pages 1 - 11
CILDIR GAKINCILAR SCTERGAONKAR V: "Chronic adipose tissue inflammation: all immune cells on the stage", TRENDS IN MOLECULAR MEDICINE., vol. 19, 2013, pages 487 - 500
XIE LORTEGA MTMORA SCHAPES SK: "Interactive changes between macrophages and adipocytes", CLINICAL AND VACCINE IMMUNOLOGY., vol. 17, 2010, pages 651 - 9, XP055766767, DOI: 10.1128/CVI.00494-09
LUMENG CNDEYOUNG SMSALTIEL AR: "Macrophages block insulin action in adipocytes by altering expression of signaling and glucose transport proteins", AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, vol. 292, 2007, pages E166 - E74
CHALASANI NYOUNOSSI ZLAVINE JECHARLTON MCUSI KRINELLA M ET AL.: "The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases", HEPATOLOGY, vol. 67, 2018, pages 328 - 57, XP055632257, DOI: 10.1002/hep.29367
ADAMS LALYMP JFSAUVER JSSANDERSON SOLINDOR KDFELDSTEIN A ET AL.: "The natural history of nonalcoholic fatty liver disease: a population-based cohort study", GASTROENTEROLOGY, vol. 129, 2005, pages 113 - 21, XP005313832, DOI: 10.1053/j.gastro.2005.04.014
MUSOLINO VGLIOZZI MSCARANO FBOSCO FSCICCHITANO MNUCERA S ET AL.: "Bergamot polyphenols improve dyslipidemia and pathophysiological features in a mouse model of non-alcoholic fatty liver disease", SCIENTIFIC REPORTS., vol. 10, 2020, pages 1 - 14
NAM J-STERABE MMAMURA MKANG M-JCHAE HSTUELTEN C ET AL.: "An anti-transforming growth factor 0 antibody suppresses metastasis via cooperative effects on multiple cell compartments", CANCER RESEARCH, vol. 68, 2008, pages 3835 - 43
TAKAHASHI KAKATSU YPODYMA-INOUE KAMATSUMOTO TTAKAHASHI HYOSHIMATSU Y ET AL.: "Targeting all transforming growth factor-(3 isoforms with an Fc chimeric receptor impairs tumor growth and angiogenesis of oral squamous cell cancer", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 295, 2020, pages 12559 - 72, XP055729675, DOI: 10.1074/jbc.RA120.012492
CHAMES PVAN REGENMORTEL MWEISS EBATY D: "Therapeutic antibodies: successes, limitations and hopes for the future", BRITISH JOURNAL OF PHARMACOLOGY., vol. 157, 2009, pages 220 - 33, XP002714017, DOI: 10.1111/j.1476-5381.2009.00190.x
BELL MRENGLEKA MJMALIK ASTRICKLER JE: "To fuse or not to fuse: what is your purpose?", PROTEIN SCIENCE, vol. 22, 2013, pages 1466 - 77, XP055692508, DOI: 10.1002/pro.2356
SANTIAGO BGUTIERREZ-CANAS IDOTOR JPALAO GLASARTE JJRUIZ J ET AL.: "Topical application of a peptide inhibitor of transforming growth factor-(31 ameliorates bleomycin-induced skin fibrosis", JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 125, 2005, pages 450 - 5, XP002604583
GALLO-OLLER GVOLLMANN-ZWERENZ AMELENDEZ BREY JAHAU PDOTOR J ET AL.: "P144, a Transforming Growth Factor beta inhibitor peptide, generates antitumoral effects and modifies SMAD7 and SKI levels in human glioblastoma cell lines", CANCER LETTERS, vol. 381, 2016, pages 67 - 75, XP029715488, DOI: 10.1016/j.canlet.2016.07.029
HUANG C-YCHUNG C-LHU T-HCHEN J-JLIU P-FCHEN C-L: "Recent progress in TGF-β inhibitors for cancer therapy", BIOMEDICINE & PHARMACOTHERAPY., vol. 134, 2021, pages 111046
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LEE, Cheo Young et al. (KR)
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