CN102076854A - 用于抑制线粒体3-磷酸甘油酰基转移酶1(mtgpat1)表达的rna拮抗剂化合物 - Google Patents

用于抑制线粒体3-磷酸甘油酰基转移酶1(mtgpat1)表达的rna拮抗剂化合物 Download PDF

Info

Publication number
CN102076854A
CN102076854A CN200980124993.0A CN200980124993A CN102076854A CN 102076854 A CN102076854 A CN 102076854A CN 200980124993 A CN200980124993 A CN 200980124993A CN 102076854 A CN102076854 A CN 102076854A
Authority
CN
China
Prior art keywords
oligomer
mtgpat1
nucleotide
nucleotide sequence
fatty liver
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN200980124993.0A
Other languages
English (en)
Chinese (zh)
Inventor
M·林德霍尔姆
E·M·斯特拉尔普
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Roche Innovation Center Copenhagen AS
Original Assignee
Santaris Pharma AS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Santaris Pharma AS filed Critical Santaris Pharma AS
Publication of CN102076854A publication Critical patent/CN102076854A/zh
Pending legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y203/00—Acyltransferases (2.3)
    • C12Y203/01—Acyltransferases (2.3) transferring groups other than amino-acyl groups (2.3.1)
    • C12Y203/01015—Glycerol-3-phosphate O-acyltransferase (2.3.1.15)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • C12N2310/334—Modified C
    • C12N2310/3341—5-Methylcytosine

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biotechnology (AREA)
  • Diabetes (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Virology (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Child & Adolescent Psychology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicinal Preparation (AREA)
CN200980124993.0A 2008-07-03 2009-06-24 用于抑制线粒体3-磷酸甘油酰基转移酶1(mtgpat1)表达的rna拮抗剂化合物 Pending CN102076854A (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US7794208P 2008-07-03 2008-07-03
EP08104623 2008-07-03
US61/077,942 2008-07-03
EP08104623.7 2008-07-03
PCT/EP2009/057907 WO2010000656A1 (en) 2008-07-03 2009-06-24 Rna antagonist compounds for the inhibition of expression of mitochondrial glycerol-3-phosphate acyltransferase 1 (mtgpat1)

Publications (1)

Publication Number Publication Date
CN102076854A true CN102076854A (zh) 2011-05-25

Family

ID=41066150

Family Applications (1)

Application Number Title Priority Date Filing Date
CN200980124993.0A Pending CN102076854A (zh) 2008-07-03 2009-06-24 用于抑制线粒体3-磷酸甘油酰基转移酶1(mtgpat1)表达的rna拮抗剂化合物

Country Status (11)

Country Link
US (1) US20120004276A1 (enExample)
EP (1) EP2310504A1 (enExample)
JP (1) JP2011526482A (enExample)
KR (1) KR20110031368A (enExample)
CN (1) CN102076854A (enExample)
AU (1) AU2009265836A1 (enExample)
BR (1) BRPI0915837A2 (enExample)
CA (1) CA2729897A1 (enExample)
EA (1) EA201170131A1 (enExample)
MX (1) MX2010013552A (enExample)
WO (1) WO2010000656A1 (enExample)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104997768A (zh) * 2015-07-23 2015-10-28 上海市第六人民医院 鱼藤酮在制备降血糖药物中的应用

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2863526T3 (es) * 2010-06-23 2021-10-11 Curna Inc Tratamiento de enfermedades relacionadas con la subunidad alfa del canal de sodio (SCNA), controlado por voltaje, mediante inhibición de la transcripción antisentido natural a SCNA
EP3260540A1 (en) 2010-11-12 2017-12-27 The General Hospital Corporation Polycomb-associated non-coding rnas
WO2012103520A1 (en) * 2011-01-28 2012-08-02 Board Of Regents Of The University Of Nebraska Methods and compositions for modulating cyclophilin d
DK2850189T3 (en) 2012-05-16 2019-02-25 Translate Bio Ma Inc COMPOSITIONS AND PROCEDURES FOR MODULATING GENEPRESSION
RU2015119411A (ru) 2012-11-15 2017-01-10 Рош Инновейшен Сентер Копенгаген А/С Конъюгаты антисмысловых соединений, направленные на аполипопротеин в
WO2014118267A1 (en) * 2013-01-30 2014-08-07 Santaris Pharma A/S Lna oligonucleotide carbohydrate conjugates
CN105039513B (zh) * 2015-05-29 2018-12-28 广州市第一人民医院 用于非酒精性脂肪肝相关目的基因多态性检测方法及其引物，以及试剂盒
EP4649951A2 (en) 2020-06-09 2025-11-19 Alnylam Pharmaceuticals, Inc. Sirna compositions and methods for silencing gpam (glycerol-3-phosphate acyltransferase 1, mitochondrial) expression
GB202015056D0 (en) * 2020-09-23 2020-11-04 Cambridge Entpr Ltd Biomarkers
MX2023009986A (es) * 2021-02-27 2023-09-06 Regeneron Pharma Tratamiento de la enfermedad hepatica con inhibidores de glicerol-3-fosfato aciltransferasa mitocondrial (gpam).
AU2022370883A1 (en) * 2021-10-22 2024-04-18 Amgen Inc. Rnai constructs for inhibiting gpam expression and methods of use thereof

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003048316A2 (en) * 2001-11-30 2003-06-12 Bristol-Myers Squibb Company Polynucleotides encoding novel human mitochondrial and microsomal glycerol-3-phosphate acyl-transferases and variants thereof
US20050053981A1 (en) * 2003-09-09 2005-03-10 Swayze Eric E. Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini
US8178503B2 (en) * 2006-03-03 2012-05-15 International Business Machines Corporation Ribonucleic acid interference molecules and binding sites derived by analyzing intergenic and intronic regions of genomes

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104997768A (zh) * 2015-07-23 2015-10-28 上海市第六人民医院 鱼藤酮在制备降血糖药物中的应用
CN104997768B (zh) * 2015-07-23 2017-11-17 上海市第六人民医院 鱼藤酮在制备降血糖药物中的应用

Also Published As

Publication number Publication date
CA2729897A1 (en) 2010-01-07
US20120004276A1 (en) 2012-01-05
EP2310504A1 (en) 2011-04-20
JP2011526482A (ja) 2011-10-13
BRPI0915837A2 (pt) 2015-11-03
WO2010000656A1 (en) 2010-01-07
AU2009265836A1 (en) 2010-01-07
MX2010013552A (es) 2011-03-24
EA201170131A1 (ru) 2011-08-30
KR20110031368A (ko) 2011-03-25

Similar Documents

Publication Publication Date Title
US7989429B2 (en) LNA antagonists targeting the androgen receptor
CN102076854A (zh) 用于抑制线粒体3-磷酸甘油酰基转移酶1(mtgpat1)表达的rna拮抗剂化合物
US8563528B2 (en) Antisense oligomers targeting PCSK9
CN104903448B (zh) 用于调节fgfr3的表达的组合物和方法
EP2444494A1 (en) RNA antagonist compounds for the modulation of PCSK9
EP2225376B1 (en) Rna antagonist compounds for the modulation of pik3ca expression
JP2014533944A (ja) Ｓｍｎ２スプライシングの調節のための化合物
WO2009127680A1 (en) Pharmaceutical composition comprising anti pcsk9 oligomers
US20110124709A1 (en) Rna antagonists targeting gli2
US9290758B2 (en) Potent anti APOB antisense compounds
WO2009043759A2 (en) Short rna antagonist compounds for the modulation of hif1alpha
US20110144185A1 (en) Rna antagonists targeting hsp27
WO2012110457A2 (en) Compounds for the modulation of osteopontin expression
EP2205738A2 (en) Short rna antagonist compounds for the modulation of hif1alpha

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C02 Deemed withdrawal of patent application after publication (patent law 2001)
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20110525