JP6393682B2 - 併用療法iii - Google Patents
併用療法iii Download PDFInfo
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- JP6393682B2 JP6393682B2 JP2015521033A JP2015521033A JP6393682B2 JP 6393682 B2 JP6393682 B2 JP 6393682B2 JP 2015521033 A JP2015521033 A JP 2015521033A JP 2015521033 A JP2015521033 A JP 2015521033A JP 6393682 B2 JP6393682 B2 JP 6393682B2
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- hdac4
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- gene silencing
- silencing agent
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Classifications
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
- A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
- A61K31/5517—1,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
-
- 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
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- 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
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering N.A.
-
- 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
- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/31—Combination therapy
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y305/00—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
- C12Y305/01—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in linear amides (3.5.1)
- C12Y305/01098—Histone deacetylase (3.5.1.98), i.e. sirtuin deacetylase
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
(式中、
R’は、H又はアルキルであり;
R’’は、H又はアルコキシであり;
R1及びR2は、Hであるか、又は一緒にオキソを形成し;
R3及びR4は、独立してH若しくはOHであるか、又は一緒にオキソを形成し;
R5、R6、R6’、R7、及びR8は、H、アルキル、アルコキシ、ヒドロキシ、ヒドロキシルアルキル、アルコキシカルボニル、モノアルキルアミノ及びジアルキルアミノからなる群から独立して選択され;
Xは、CH2又はOであり;
nは、0又は1である)
を有する。
からなる群から選択される。
(式中、
R’は、H又はアルキルであり;
R’’は、H又はアルコキシであり;
R1及びR2は、Hであるか、又は一緒にオキソを形成し;
R3及びR4は、独立してH若しくはOHであるか、又は一緒にオキソを形成し;
R5、R6、R6’、R7、及びR8は、独立して、H、アルキル、アルコキシ、ヒドロキシ、ヒドロキシルアルキル、アルコキシカルボニル、モノアルキルアミノ及びジアルキルアミノからなる群から選択され;
Xは、CH2又はOであり;
nは、0又は1である)を有する。
真核生物の細胞培養及び小分子干渉RNA(siRNA)のトランスフェクション:本試験のために、T98Gヒトグリア芽細胞腫細胞系を使用した。37℃、5%CO2の加湿雰囲気内で、10%熱不活性化FCS及びペニシリン(100単位/mL)−ストレプトマイシン(100Ag/mL)を加えたイーグル(Eagle)のMEM(Sigma−Aldrich)で細胞を培養した。製造業者の使用説明書に従って、リポフェクトアミン(Lipofectamine)RNAiMAX試薬(Invitrogen)を用いて、小分子干渉RNA(siRNA又はdsRNA)トランスフェクションを実施した。トランスフェクションは、フォワードトランスフェクションプロトコルを用いて実施した。以下のsiRNA配列を使用した:スクランブルされた(5’−GUA ACA AUG AGA GCA CGG C−3’;配列番号171)、HDAC4(5’−UCA UAC ACG AGG CCU GUC GUU−3’;配列番号2)、HDAC4.2(5’−AAA UUA CGG UCC AGG CUA AUU−3’;配列番号5)。
がん細胞の生存及び異なる化学薬剤への感受性に及ぼすHDAC4阻害の影響を研究するために、まずは、ヒトグリア芽細胞腫T98G細胞を、スクランブルsiRNA(配列番号171に表される非標的siRNA)又はHDAC4特異的siRNA(配列番号2に表される)で72時間、一時的にトランスフェクトさせた。HDAC4特異的siRNAによる有効なタンパク質の下方制御を、免疫ブロット法によって示した(図1A)。
Claims (18)
- 少なくとも1種類のHDAC4遺伝子サイレンシング剤と、
からなる群から選択される化合物とを含む、医薬組成物。 - 少なくとも1種類のHDAC4遺伝子サイレンシング剤と組合せて使用するための、
からなる群から選択される化合物を含む、医薬組成物。 -
からなる群から選択される化合物と組合せて使用するための、少なくとも1種類のHDAC4遺伝子サイレンシング剤を含む、医薬組成物。 - 前記HDAC4遺伝子サイレンシング剤が、siRNA分子、DsiRNA分子、人工miRNA前駆体、shRNA分子、アンチセンスオリゴヌクレオチド、及びリボザイムからなる群から選択される、請求項1〜3の何れか1項に記載の医薬組成物。
- 前記HDAC4遺伝子サイレンシング剤が、配列番号1から170からなる群から選択される核酸配列を含む、請求項1〜3の何れか1項に記載の医薬組成物。
- 過剰増殖性疾患を処置するための、請求項1〜5の何れか1項に記載の医薬組成物。
- 脳がん、神経膠腫、星状細胞腫、及びグリア芽細胞腫からなる群から選択される過剰増殖性疾患の処置で用いるための、請求項1〜5の何れか1項に記載の医薬組成物。
- 前記HDAC4遺伝子サイレンシング剤及び前記化合物が、同時に、逐次に、又は別々に投与される、請求項1から7までのいずれか一項に記載の医薬組成物。
- 少なくとも1つの薬学的に許容される担体を含む、請求項1から8までのいずれか一項に記載の医薬組成物。
- 医薬組成物を調製するための、少なくとも1種類のHDAC4遺伝子サイレンシング剤と、
からなる群から選択される化合物との使用。 - 少なくとも1種類のHDAC4遺伝子サイレンシング剤と組合せて使用する医薬組成物を調製するための、
からなる群から選択される化合物の使用。 -
からなる群から選択される化合物と組合せて使用する医薬組成物を調製するための、少なくとも1種類のHDAC4遺伝子サイレンシング剤の使用。 - 前記HDAC4遺伝子サイレンシング剤が、siRNA分子、DsiRNA分子、人工miRNA前駆体、shRNA分子、アンチセンスオリゴヌクレオチド、及びリボザイムからなる群から選択される、請求項10〜12の何れか1項に記載の使用。
- 前記HDAC4遺伝子サイレンシング剤が、配列番号1から170からなる群から選択される核酸配列を含む、請求項10〜12の何れか1項に記載の使用。
- 前記医薬組成物は、過剰増殖性疾患を処置するために用いられる、請求項10〜14の何れか1項に記載の使用。
- 前記医薬組成物は、脳がん、神経膠腫、星状細胞腫、及びグリア芽細胞腫からなる群から選択される過剰増殖性疾患の処置で用いるための、請求項10〜14の何れか1項に記載の使用。
- 前記HDAC4遺伝子サイレンシング剤及び前記化合物が、同時に、逐次に、又は別々に投与される、請求項10から16までのいずれか一項に記載の使用。
- 前記医薬組成物は、少なくとも1つの薬学的に許容される担体を含む、請求項10から17までのいずれか一項に記載の使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FI20125795 | 2012-07-13 | ||
FI20125795 | 2012-07-13 | ||
PCT/FI2013/050745 WO2014009609A1 (en) | 2012-07-13 | 2013-07-11 | Combination therapy iii |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2015527316A JP2015527316A (ja) | 2015-09-17 |
JP2015527316A5 JP2015527316A5 (ja) | 2016-09-01 |
JP6393682B2 true JP6393682B2 (ja) | 2018-09-19 |
Family
ID=48917570
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015521033A Expired - Fee Related JP6393682B2 (ja) | 2012-07-13 | 2013-07-11 | 併用療法iii |
Country Status (8)
Country | Link |
---|---|
US (1) | US10166241B2 (ja) |
EP (1) | EP2872631B1 (ja) |
JP (1) | JP6393682B2 (ja) |
CN (1) | CN104619845A (ja) |
CA (1) | CA2878873C (ja) |
DK (1) | DK2872631T3 (ja) |
ES (1) | ES2627500T3 (ja) |
WO (1) | WO2014009609A1 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106344923B (zh) * | 2016-09-23 | 2019-09-27 | 中国人民解放军第二军医大学第二附属医院 | 组蛋白去乙酰化酶-4抑制剂在制备治疗多发性骨髓瘤疾病药物中的应用 |
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JP2002526450A (ja) * | 1998-09-18 | 2002-08-20 | スミスクライン・ビーチャム・コーポレイション | Chk1キナーゼ阻害物質 |
US6214986B1 (en) | 1998-10-07 | 2001-04-10 | Isis Pharmaceuticals, Inc. | Antisense modulation of bcl-x expression |
US20030190635A1 (en) | 2002-02-20 | 2003-10-09 | Mcswiggen James A. | RNA interference mediated treatment of Alzheimer's disease using short interfering RNA |
EP1386004A4 (en) | 2001-04-05 | 2005-02-16 | Ribozyme Pharm Inc | MODULATION OF GENE EXPRESSION ASSOCIATED WITH INFLAMMATORY PROLIFERATION AND GROWTH OF NEURITIES BY METHODS INVOLVING NUCLEIC ACID |
US20040019001A1 (en) | 2002-02-20 | 2004-01-29 | Mcswiggen James A. | RNA interference mediated inhibition of protein typrosine phosphatase-1B (PTP-1B) gene expression using short interfering RNA |
US20030175950A1 (en) | 2001-05-29 | 2003-09-18 | Mcswiggen James A. | RNA interference mediated inhibition of HIV gene expression using short interfering RNA |
US7488712B2 (en) * | 2002-02-20 | 2009-02-10 | Kyushu Institute Of Technology | Histone deacetylase inhibitors and methods for producing the same |
WO2004017991A1 (en) | 2002-08-13 | 2004-03-04 | Cell Center Cologne Gmbh | Use of iap for the diagnosis and of iap-inhibitors for the treatment of hodgkin’s lymphomas |
WO2004028471A2 (en) | 2002-09-28 | 2004-04-08 | Massachusetts Institute Of Technology | Influenza therapeutic |
US20040077083A1 (en) * | 2002-10-17 | 2004-04-22 | Isis Pharmaceuticals Inc. | Antisense modulation of histone deacetylase 4 expression |
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EP1560931B1 (en) | 2002-11-14 | 2011-07-27 | Dharmacon, Inc. | Functional and hyperfunctional sirna |
CA2523517C (en) | 2003-04-25 | 2013-07-30 | Dana-Farber Cancer Institute, Inc. | Bcl2l12 polypeptide activators and inhibitors |
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WO2005011598A2 (en) | 2003-07-31 | 2005-02-10 | University Of South Florida | Leukemia treatment method and composition |
CN100536850C (zh) * | 2003-08-08 | 2009-09-09 | 诺瓦提斯公司 | 包含星孢素的组合 |
MX2007001155A (es) | 2004-07-29 | 2007-08-14 | Creabilis Therapeutics Spa | Uso de inhibidores de k-252a y de quinasa para la prevencion o el tratamiento de patologias asociadas con hmgb1. |
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-
2013
- 2013-07-11 CN CN201380047501.9A patent/CN104619845A/zh active Pending
- 2013-07-11 WO PCT/FI2013/050745 patent/WO2014009609A1/en active Application Filing
- 2013-07-11 US US14/414,393 patent/US10166241B2/en not_active Expired - Fee Related
- 2013-07-11 ES ES13745446.8T patent/ES2627500T3/es active Active
- 2013-07-11 CA CA2878873A patent/CA2878873C/en not_active Expired - Fee Related
- 2013-07-11 EP EP13745446.8A patent/EP2872631B1/en not_active Not-in-force
- 2013-07-11 JP JP2015521033A patent/JP6393682B2/ja not_active Expired - Fee Related
- 2013-07-11 DK DK13745446.8T patent/DK2872631T3/en active
Also Published As
Publication number | Publication date |
---|---|
EP2872631A1 (en) | 2015-05-20 |
JP2015527316A (ja) | 2015-09-17 |
CA2878873C (en) | 2018-08-21 |
CN104619845A (zh) | 2015-05-13 |
EP2872631B1 (en) | 2017-05-03 |
CA2878873A1 (en) | 2014-01-16 |
DK2872631T3 (en) | 2017-06-12 |
US10166241B2 (en) | 2019-01-01 |
US20150209369A1 (en) | 2015-07-30 |
ES2627500T3 (es) | 2017-07-28 |
WO2014009609A1 (en) | 2014-01-16 |
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