Title:
TARGET FOR SCREENING DRUG FOR INHIBITING INTESTINAL FATTY ACID INTAKE AND PREVENTING FATTY LIVER, AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2023/098273
Kind Code:
A1
Abstract:
Disclosed are a target for screening a drug for inhibiting the intestinal fatty acid intake and preventing fatty liver, and the use thereof. According to a knockout mouse experiment, provided in the present invention are a target Soat2 (Sterol O-acyl transferase) of drug action, and a drug screening model thereof. The inhibitory effect of a drug compound on Soat2 is determined by means of combined screening of high-throughput NBD-cholesterol screening, PCR and BODIPYTM FL C16 fluorescence. The drug compound with strong lipid-lowering effects and few toxic side effects can be screened out from the level of intestinal fatty acid intake by means of the drug screening model using Soat2 as the target.
Inventors:
GU AIHUA (CN)
JIANG ZHAOYAN (CN)
SHAO WENTAO (CN)
LIANG JINGJIA (CN)
LIU QIAN (CN)
JIANG ZHAOYAN (CN)
SHAO WENTAO (CN)
LIANG JINGJIA (CN)
LIU QIAN (CN)
Application Number:
PCT/CN2022/122617
Publication Date:
June 08, 2023
Filing Date:
September 29, 2022
Export Citation:
Assignee:
UNIV NANJING MEDICAL (CN)
International Classes:
C12Q1/02; A61K45/00; A61P1/16; A61P3/04; A61P3/06; C12N5/09; C12Q1/48; C12Q1/6851
Foreign References:
| US20160367537A1 | 2016-12-22 | |||
| CN110177573A | 2019-08-27 | |||
| CN114164249A | 2022-03-11 |
Other References:
ALGER, H. M. ET AL.: "Inhibition of Acyl-Coenzyme A: Cholesterol Acyltransferase 2 (ACAT2) Prevents Dietary Cholesterol-associated Steatosis by Enhancing Hepatic Triglyceride Mobilization.", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 285, no. 19, 7 May 2010 (2010-05-07), XP002659713, DOI: 10.1074/JBC.M110.118422
MELCHIOR JOHN T., OLSON JOHN D., KELLEY KATHRYN L., WILSON MARTHA D., SAWYER JANET K., LINK KERRY M., RUDEL LAWRENCE L.: "Targeted Knockdown of Hepatic SOAT2 With Antisense Oligonucleotides Stabilizes Atherosclerotic Plaque in ApoB100-only LDLr −/− Mice", TRANSLATIONAL SCIENCES, LIPPINCOTT, WILLIAMS & WILKINS, vol. 35, no. 9, 1 September 2015 (2015-09-01), pages 1920 - 1927, XP093068857, ISSN: 1079-5642, DOI: 10.1161/ATVBAHA.115.305747
BELL THOMAS A., BROWN J. MARK, GRAHAM MARK J., LEMONIDIS KRISTINA M., CROOKE ROSANNE M., RUDEL LAWRENCE L.: "Liver-Specific Inhibition of Acyl-Coenzyme A:Cholesterol Acyltransferase 2 With Antisense Oligonucleotides Limits Atherosclerosis Development in Apolipoprotein B100–Only Low-Density Lipoprotein Receptor −/− Mice", TRANSLATIONAL SCIENCES, LIPPINCOTT, WILLIAMS & WILKINS, vol. 26, no. 8, 1 August 2006 (2006-08-01), pages 1814 - 1820, XP093068858, ISSN: 1079-5642, DOI: 10.1161/01.ATV.0000225289.30767.06
CAMILLA PRAMFALK; MATS ERIKSSON; PAOLO PARINI: "Cholesteryl esters and ACAT", EUROPEAN JOURNAL OF LIPID SCIENCE TECHNOLOGY, WILEY VCH VERLAG, WEINHEIM., DE, vol. 114, no. 6, 19 April 2012 (2012-04-19), DE , pages 624 - 633, XP072145860, ISSN: 1438-7697, DOI: 10.1002/ejlt.201100294
MELCHIOR JOHN T., OLSON JOHN D., KELLEY KATHRYN L., WILSON MARTHA D., SAWYER JANET K., LINK KERRY M., RUDEL LAWRENCE L.: "Targeted Knockdown of Hepatic SOAT2 With Antisense Oligonucleotides Stabilizes Atherosclerotic Plaque in ApoB100-only LDLr −/− Mice", TRANSLATIONAL SCIENCES, LIPPINCOTT, WILLIAMS & WILKINS, vol. 35, no. 9, 1 September 2015 (2015-09-01), pages 1920 - 1927, XP093068857, ISSN: 1079-5642, DOI: 10.1161/ATVBAHA.115.305747
BELL THOMAS A., BROWN J. MARK, GRAHAM MARK J., LEMONIDIS KRISTINA M., CROOKE ROSANNE M., RUDEL LAWRENCE L.: "Liver-Specific Inhibition of Acyl-Coenzyme A:Cholesterol Acyltransferase 2 With Antisense Oligonucleotides Limits Atherosclerosis Development in Apolipoprotein B100–Only Low-Density Lipoprotein Receptor −/− Mice", TRANSLATIONAL SCIENCES, LIPPINCOTT, WILLIAMS & WILKINS, vol. 26, no. 8, 1 August 2006 (2006-08-01), pages 1814 - 1820, XP093068858, ISSN: 1079-5642, DOI: 10.1161/01.ATV.0000225289.30767.06
CAMILLA PRAMFALK; MATS ERIKSSON; PAOLO PARINI: "Cholesteryl esters and ACAT", EUROPEAN JOURNAL OF LIPID SCIENCE TECHNOLOGY, WILEY VCH VERLAG, WEINHEIM., DE, vol. 114, no. 6, 19 April 2012 (2012-04-19), DE , pages 624 - 633, XP072145860, ISSN: 1438-7697, DOI: 10.1002/ejlt.201100294
Attorney, Agent or Firm:
NANJING TIANHUA PATENT AGENT CO., LTD. (CN)
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