Title:
USE OF GGPP BINDING AND ALLOSTERIC ACTIVATION OF HUMAN FBP1 IN PREPARATION OF ANTI-HEPATOCELLULAR CARCINOMA DRUG
Document Type and Number:
WIPO Patent Application WO/2023/024351
Kind Code:
A1
Abstract:
Provided is the use of GGPP binding and allosteric activation of human FBP1 in the preparation of an anti-hepatocellular carcinoma drug。 The amino acid sequence of the human FBP1 protein is as shown in SEQ ID No. 1. A direct binding protein action network of GGPP in a normal liver is established, and a plurality of GGPP binding proteins involved in the regulation of hepatic glycolipid metabolism are screened and verified. The GGPP specifically binds to FBP1 and up-regulates the enzyme activity of FBP1 to promote gluconeogenesis, and can inhibit the migration of hepatocytes and hepatoma cells. The GGPP can regulate the molecular mechanism of the occurrence and development of hepatocellular carcinoma by means of sensitizing the metabolic balance of a target protein FBP1-coupled glycolipid, which can be applied to the treatment of hepatocellular carcinoma. GGPP regulates the metabolic balance of a hepatic glycolipid by means of specifically and directly binding to a target protein FBP1 thereof, and provides a new potential target, drug and treatment method for the treatment of HCC.
Inventors:
FANG LEI (CN)
ZHANG JINGZI (CN)
LI CHAOJUN (CN)
ZHAO YUE (CN)
ZHANG JINGZI (CN)
LI CHAOJUN (CN)
ZHAO YUE (CN)
Application Number:
PCT/CN2021/139760
Publication Date:
March 02, 2023
Filing Date:
December 20, 2021
Export Citation:
Assignee:
NANJING UNIVERSITY OF TECHNOLOGY (CN)
International Classes:
A61K31/663; A61P35/00
Foreign References:
| CN113694072A | 2021-11-26 | |||
| CN112955174A | 2021-06-11 |
Other References:
FANG, L.: "GGPP allosterically activates FBP1 homotetramer to suppress the onset and progression of hepatocellular carcinoma", THE 10TH CHNIA HUMAN PROTEOME ORGANISATION CONGRESS, THIRD ROUND NOTIFICATION, 17 November 2018 (2018-11-17)
"Doctoral Dissertation", 1 January 2018, NANJING UNIVERSITY, CN, article LIU, JIA: "Geranylgeranyl Diphosphate synthase（GGPPS）Regulates Hepatocellular Carcinogenesis by Targeting Glucose Metabolism", pages: 1 - 125, XP009544021, DOI: 10.27235/d.cnki.gnjiu.2018.000547
LI FUMING; HUANGYANG PEIWEI; BURROWS MICHELLE; GUO KATHY; RISCAL ROMAIN; GODFREY JASON; LEE KYOUNG EUN; LIN NAN; LEE PEARL; BLAIR : "FBP1 loss disrupts liver metabolism and promotes tumorigenesis through a hepatic stellate cell senescence secretome", NATURE CELL BIOLOGY, NATURE PUBLISHING GROUP UK, LONDON, vol. 22, no. 6, 4 May 2020 (2020-05-04), London, pages 728 - 739, XP037159232, ISSN: 1465-7392, DOI: 10.1038/s41556-020-0511-2
LIU GAO-MIN, ZHANG YAO-MING: "Targeting FBPase is an emerging novel approach for cancer therapy", CANCER CELL INTERNATIONAL, vol. 18, no. 1, 1 December 2018 (2018-12-01), pages 36, XP093038858, DOI: 10.1186/s12935-018-0533-z
DANIEL D. WALLER, JAEOK PARK, YOULA S. TSANTRIZOS: "Inhibition of farnesyl pyrophosphate (FPP) and/or geranylgeranyl pyrophosphate (GGPP) biosynthesis and its implication in the treatment of cancers", ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY., SWETS AND ZEITLINGER, LISSE., NL, vol. 54, no. 1, 18 February 2019 (2019-02-18), NL , pages 41 - 60, XP009543783, ISSN: 1381-3455, DOI: 10.1080/10409238.2019.1568964
"Doctoral Dissertation", 1 January 2018, NANJING UNIVERSITY, CN, article LIU, JIA: "Geranylgeranyl Diphosphate synthase（GGPPS）Regulates Hepatocellular Carcinogenesis by Targeting Glucose Metabolism", pages: 1 - 125, XP009544021, DOI: 10.27235/d.cnki.gnjiu.2018.000547
LI FUMING; HUANGYANG PEIWEI; BURROWS MICHELLE; GUO KATHY; RISCAL ROMAIN; GODFREY JASON; LEE KYOUNG EUN; LIN NAN; LEE PEARL; BLAIR : "FBP1 loss disrupts liver metabolism and promotes tumorigenesis through a hepatic stellate cell senescence secretome", NATURE CELL BIOLOGY, NATURE PUBLISHING GROUP UK, LONDON, vol. 22, no. 6, 4 May 2020 (2020-05-04), London, pages 728 - 739, XP037159232, ISSN: 1465-7392, DOI: 10.1038/s41556-020-0511-2
LIU GAO-MIN, ZHANG YAO-MING: "Targeting FBPase is an emerging novel approach for cancer therapy", CANCER CELL INTERNATIONAL, vol. 18, no. 1, 1 December 2018 (2018-12-01), pages 36, XP093038858, DOI: 10.1186/s12935-018-0533-z
DANIEL D. WALLER, JAEOK PARK, YOULA S. TSANTRIZOS: "Inhibition of farnesyl pyrophosphate (FPP) and/or geranylgeranyl pyrophosphate (GGPP) biosynthesis and its implication in the treatment of cancers", ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY., SWETS AND ZEITLINGER, LISSE., NL, vol. 54, no. 1, 18 February 2019 (2019-02-18), NL , pages 41 - 60, XP009543783, ISSN: 1381-3455, DOI: 10.1080/10409238.2019.1568964
Attorney, Agent or Firm:
JIANGSU YINCHUANG LAW FIRM (CN)
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