Title:
USE OF MICROCYSTINS IN PREPARATION OF DRUGS FOR PREVENTING OR TREATING ORGAN AND TISSUE FIBROSIS DISEASES
Document Type and Number:
WIPO Patent Application WO/2018/099148
Kind Code:
A1
Abstract:
Use of microcystins having a monocyclic heptapeptide structure in preparation of drugs for preventing or treating organ and tissue fibrosis diseases. Preferably, the microcystins are microcystins-LR with amino acids at positions 2 and 4 of a monocyclic heptapeptide structure thereof being leucine and arginine respectively, or are microcystins-RR with amino acids at positions 2 and 4 thereof being both arginine. Also provided is a method for inhibiting myofibroblast differentiation and collagen synthesis. The method is implemented by inhibiting a TGF-β/Smad signal pathway by using one or more microcystins.
Inventors:
WANG YAPING (CN)
XU LIZHI (CN)
WANG JIE (CN)
ZHAO QINGYA (CN)
XU LIZHI (CN)
WANG JIE (CN)
ZHAO QINGYA (CN)
Application Number:
PCT/CN2017/099249
Publication Date:
June 07, 2018
Filing Date:
August 28, 2017
Export Citation:
Assignee:
UNIV NANJING (CN)
International Classes:
A61K38/12; A61P11/00
Foreign References:
| CN106620647A | 2017-05-10 | |||
| US20140271923A1 | 2014-09-18 | |||
| CN102524180A | 2012-07-04 |
Other References:
DING, XIAOSHENG: "Research Progress on Microcystin and Its Kidney Toxicity", JOURNAL OF ANHUI AGRICULTURAL SCIENCES, vol. 36, no. 31, 31 December 2008 (2008-12-31), pages 13506 - 13507, XP9515681
LI, XIAOYU ET AL.: "Research Progress on Relationship between Microcystin and Human Health", CHINESE JOURNAL OF PUBLIC HEALTH, vol. 24, no. 08, 31 August 2008 (2008-08-31), pages 1016 - 1017, XP009515845, ISSN: 1001-0580
GUZMAN, R.E. ET AL.: "Hepatic Oxidative Stress Following Prolonged Sublethal Microcystin LR Exposure", TOXICOLOGIC PATHOLOGY, vol. 27, no. 5, 31 December 1999 (1999-12-31), pages 582 - 588, XP055490319, Retrieved from the Internet
WALLACE KBURT ADWRIGHT MC: "Liver fibrosis", BIOCHEM J, vol. 411, no. 1, 2008, pages 1
LEBLEU VSTADURI GO'CONNELL JTENG YCOOKE VGWODA CSUGIMOTO HKALLURI R: "Origin and function of myofibroblasts in kidney fibrosis", NAT MED, vol. 19, no. 8, 2013, pages 1047 - 53
MENG XMTANG PMLI JLAN HY: "TGF-p/Smad signaling in renal fibrosis", FRONT PHYSIOL, vol. 6, 2015, pages 82
HUTCHINSON JFOGARTY AHUBBARD RMCKEEVER T.: "Global incidence and mortality of idiopathic pulmonary firosis: a systematic review", EUR RESPIR, vol. 46, no. 3, 2015, pages 795
BAUMGARTNER KBSAMET JMCOULTAS DBSTIDLEY CAHUNT WCCOLBY TVWALDRON JA: "Occupational and environmental risk factors for idiopathic pulmonary firosis: a multicenter case-control study", AM J EPIDEMIOL, vol. 152, no. 4, 2000, pages 307
KING TJPARDO ASELMAN M: "Idiopathic pulmonary fibrosis", LANCET, vol. 378, no. 9807, 2011, pages 1949, XP055227094, DOI: doi:10.1016/S0140-6736(11)60052-4
TAGER AMLACAMERA PSHEA BSCAMPANELLA GSSELMAN MZHAO ZPOLOSUKHIN VWAIN JKARIMI-SHAH B AKIM ND: "The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak", NAT MED, vol. 14, 2008, pages 45
ZHANG HLIU XFCHEN SWU JHYE XXU LZCHEN HMZHANG DPTAN RXWANG YP: "Tectorigenin inhibits the in vitro proliferation and enhances miR-338* expression of pulmonary fibroblasts in rats with idiopathic pulmonary fibrosis", J ETHNOPHARMACOL, vol. 131, no. 1, 2010, pages 165
VAN APELDOOM MEVAN EGMOND HPSPEIJERS GJBAKKER GJ: "Toxins of cyanobacteria", MOL NUTR FOOD RES, vol. 51, no. 1, 2007, pages 7 - 60
WOLF HUFRANK C: "Toxicity assessment of cyanobacterial toxin mixtures", ENVIRON TOXICOL, vol. 17, 2002, pages 395 - 399
ALLISON SJ: "Fibrosis: the source of myofibroblasts in kidney fibrosis", NAT. REV. NEPHROL, vol. 9, 2013, pages 494
KALLURI RNEILSON EG: "Epithelial-mesenchymal transition and its implications for fibrosis", J CLIN INVEST, vol. 112, 2003, pages 1776, XP002988689, DOI: doi:10.1172/JCI200320530
LAN HY: "Diverse roles of TGF-p/Smads in renal fibrosis and inflammation", INT J BIOL SCI, vol. 7, no. 7, 2011, pages 1056
YAN XLIU ZCHEN Y: "Regulation of TGF-beta signaling by Smad7", ACTA BIOCHIM BIOPHYS SIN (SHANGHAI, vol. 41, no. 4, 2009, pages 263
LUO YXU WCHEN HWARBURTON DDONG RQIAN BSELMAN MGAULDIE JKOLB MSHI W: "A novel profibrotic mechanism mediated by TGF-P -stimulated collagen prolyl hydroxylase expression in fibrotic lung mesenchymal cells", J PATHOL, vol. 236, no. 3, 2015, pages 384
WEMIG GCHEN SYCUI LVAN NESTE CTSAI JMKAMBHAM NVOGEL HNATKUNAM YGILLILAND DGNOLAN G: "Unifying mechanism for different fibrotic diseases", PROC NATL ACAD SCI USA, vol. 114, no. 18, 2017, pages 4757, XP055459914, DOI: doi:10.1073/pnas.1621375114
ANGUIANO LRIERA MPASCUAL JSOLER MJ: "Endothelin Blockade in Diabetic Kidney Disease", J CLIN MED, vol. 4, no. 6, 2015, pages 1171
See also references of EP 3549596A4
LI, XIAOYU ET AL.: "Research Progress on Relationship between Microcystin and Human Health", CHINESE JOURNAL OF PUBLIC HEALTH, vol. 24, no. 08, 31 August 2008 (2008-08-31), pages 1016 - 1017, XP009515845, ISSN: 1001-0580
GUZMAN, R.E. ET AL.: "Hepatic Oxidative Stress Following Prolonged Sublethal Microcystin LR Exposure", TOXICOLOGIC PATHOLOGY, vol. 27, no. 5, 31 December 1999 (1999-12-31), pages 582 - 588, XP055490319, Retrieved from the Internet
WALLACE KBURT ADWRIGHT MC: "Liver fibrosis", BIOCHEM J, vol. 411, no. 1, 2008, pages 1
LEBLEU VSTADURI GO'CONNELL JTENG YCOOKE VGWODA CSUGIMOTO HKALLURI R: "Origin and function of myofibroblasts in kidney fibrosis", NAT MED, vol. 19, no. 8, 2013, pages 1047 - 53
MENG XMTANG PMLI JLAN HY: "TGF-p/Smad signaling in renal fibrosis", FRONT PHYSIOL, vol. 6, 2015, pages 82
HUTCHINSON JFOGARTY AHUBBARD RMCKEEVER T.: "Global incidence and mortality of idiopathic pulmonary firosis: a systematic review", EUR RESPIR, vol. 46, no. 3, 2015, pages 795
BAUMGARTNER KBSAMET JMCOULTAS DBSTIDLEY CAHUNT WCCOLBY TVWALDRON JA: "Occupational and environmental risk factors for idiopathic pulmonary firosis: a multicenter case-control study", AM J EPIDEMIOL, vol. 152, no. 4, 2000, pages 307
KING TJPARDO ASELMAN M: "Idiopathic pulmonary fibrosis", LANCET, vol. 378, no. 9807, 2011, pages 1949, XP055227094, DOI: doi:10.1016/S0140-6736(11)60052-4
TAGER AMLACAMERA PSHEA BSCAMPANELLA GSSELMAN MZHAO ZPOLOSUKHIN VWAIN JKARIMI-SHAH B AKIM ND: "The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak", NAT MED, vol. 14, 2008, pages 45
ZHANG HLIU XFCHEN SWU JHYE XXU LZCHEN HMZHANG DPTAN RXWANG YP: "Tectorigenin inhibits the in vitro proliferation and enhances miR-338* expression of pulmonary fibroblasts in rats with idiopathic pulmonary fibrosis", J ETHNOPHARMACOL, vol. 131, no. 1, 2010, pages 165
VAN APELDOOM MEVAN EGMOND HPSPEIJERS GJBAKKER GJ: "Toxins of cyanobacteria", MOL NUTR FOOD RES, vol. 51, no. 1, 2007, pages 7 - 60
WOLF HUFRANK C: "Toxicity assessment of cyanobacterial toxin mixtures", ENVIRON TOXICOL, vol. 17, 2002, pages 395 - 399
ALLISON SJ: "Fibrosis: the source of myofibroblasts in kidney fibrosis", NAT. REV. NEPHROL, vol. 9, 2013, pages 494
KALLURI RNEILSON EG: "Epithelial-mesenchymal transition and its implications for fibrosis", J CLIN INVEST, vol. 112, 2003, pages 1776, XP002988689, DOI: doi:10.1172/JCI200320530
LAN HY: "Diverse roles of TGF-p/Smads in renal fibrosis and inflammation", INT J BIOL SCI, vol. 7, no. 7, 2011, pages 1056
YAN XLIU ZCHEN Y: "Regulation of TGF-beta signaling by Smad7", ACTA BIOCHIM BIOPHYS SIN (SHANGHAI, vol. 41, no. 4, 2009, pages 263
LUO YXU WCHEN HWARBURTON DDONG RQIAN BSELMAN MGAULDIE JKOLB MSHI W: "A novel profibrotic mechanism mediated by TGF-P -stimulated collagen prolyl hydroxylase expression in fibrotic lung mesenchymal cells", J PATHOL, vol. 236, no. 3, 2015, pages 384
WEMIG GCHEN SYCUI LVAN NESTE CTSAI JMKAMBHAM NVOGEL HNATKUNAM YGILLILAND DGNOLAN G: "Unifying mechanism for different fibrotic diseases", PROC NATL ACAD SCI USA, vol. 114, no. 18, 2017, pages 4757, XP055459914, DOI: doi:10.1073/pnas.1621375114
ANGUIANO LRIERA MPASCUAL JSOLER MJ: "Endothelin Blockade in Diabetic Kidney Disease", J CLIN MED, vol. 4, no. 6, 2015, pages 1171
See also references of EP 3549596A4
Attorney, Agent or Firm:
BEI&OCEAN (CN)
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