JP6637884B2 - ブロモドメインおよびエクストラターミナル(bet)タンパク質インヒビターを使用するがんのための併用療法 - Google Patents

ブロモドメインおよびエクストラターミナル(bet)タンパク質インヒビターを使用するがんのための併用療法 Download PDF

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JP6637884B2
JP6637884B2 JP2016528821A JP2016528821A JP6637884B2 JP 6637884 B2 JP6637884 B2 JP 6637884B2 JP 2016528821 A JP2016528821 A JP 2016528821A JP 2016528821 A JP2016528821 A JP 2016528821A JP 6637884 B2 JP6637884 B2 JP 6637884B2
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cancer
therapy
therapeutic agent
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agent
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JP2016535756A (ja
JP2016535756A5 (https=
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ブラドナー,ジェームス,イー.
マキューン,マイケル,アール.
シップ,マーガレット,エー.
シャピュイ,ビョルン
ウォン,クァク,キン
チェン,ツァオ
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Dana Farber Cancer Institute Inc
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404Indoles, e.g. pindolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/436Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • A61K31/4523Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/453Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • A61K31/4523Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D495/00Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/12Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D495/14Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
JP2016528821A 2013-11-08 2014-11-07 ブロモドメインおよびエクストラターミナル(bet)タンパク質インヒビターを使用するがんのための併用療法 Active JP6637884B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361901908P 2013-11-08 2013-11-08
US61/901,908 2013-11-08
PCT/US2014/064549 WO2015070020A2 (en) 2013-11-08 2014-11-07 Combination therapy for cancer using bromodomain and extra-terminal (bet) protein inhibitors

Publications (3)

Publication Number Publication Date
JP2016535756A JP2016535756A (ja) 2016-11-17
JP2016535756A5 JP2016535756A5 (https=) 2017-12-14
JP6637884B2 true JP6637884B2 (ja) 2020-01-29

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JP2016528821A Active JP6637884B2 (ja) 2013-11-08 2014-11-07 ブロモドメインおよびエクストラターミナル(bet)タンパク質インヒビターを使用するがんのための併用療法

Country Status (9)

Country Link
US (2) US11446309B2 (https=)
EP (1) EP3066101B1 (https=)
JP (1) JP6637884B2 (https=)
KR (1) KR20160072261A (https=)
CN (1) CN105849110B (https=)
CA (1) CA2929652A1 (https=)
MX (1) MX379463B (https=)
RU (1) RU2016122654A (https=)
WO (1) WO2015070020A2 (https=)

Families Citing this family (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL2902030T3 (pl) 2010-05-14 2017-07-31 Dana-Farber Cancer Institute, Inc. Związki tienotriazolodiazepinowe do leczenia nowotworu
MX354217B (es) 2010-05-14 2018-02-19 Dana Farber Cancer Inst Inc Composiciones y metodos para el tratamiento de leucemia.
CA2929652A1 (en) 2013-11-08 2015-05-14 Dana-Farber Cancer Institute, Inc. Combination therapy for cancer using bromodomain and extra-terminal (bet) protein inhibitors
SG11201607108XA (en) 2014-02-28 2016-09-29 Tensha Therapeutics Inc Treatment of conditions associated with hyperinsulinaemia
WO2015183932A1 (en) * 2014-05-29 2015-12-03 Memorial Sloan Kettering Cancer Center Drug combinations for treatment of melanoma and other cancers
BR112017008714A2 (pt) 2014-10-27 2017-12-19 Tensha Therapeutics Inc inibidores de bromodomínio
EP3215135B1 (en) * 2014-11-07 2020-05-13 Tolero Pharmaceuticals, Inc. Methods to target transcriptional control at super-enhancer regions
CA2969417A1 (en) 2014-12-05 2016-06-09 H. Lee Moffitt Cancer Center And Research Institute, Inc. Bromodomain inhibitor as adjuvant in cancer immunotherapy
US9901574B2 (en) 2015-04-20 2018-02-27 Tolero Pharmaceuticals, Inc. Predicting response to alvocidib by mitochondrial profiling
ES2739749T3 (es) 2015-05-18 2020-02-03 Tolero Pharmaceuticals Inc Profármacos de alvocidib que tienen biodisponibilidad aumentada
WO2017015027A1 (en) * 2015-07-20 2017-01-26 Mayo Foundation For Medical Education And Research Methods and materials for treating cancer
MX2018001289A (es) 2015-08-03 2018-04-30 Tolero Pharmaceuticals Inc Terapias de combinacion para el tratamiento del cancer.
AU2016304856B8 (en) * 2015-08-10 2021-02-18 Dana-Farber Cancer Institute, Inc. Mechanism of resistance to BET bromodomain inhibitors
CN107921039A (zh) * 2015-08-19 2018-04-17 卫材R&D管理有限公司 用于胆道癌的治疗剂
CN109462980B (zh) * 2016-03-15 2022-02-08 奥莱松基因组股份有限公司 用于治疗血液恶性肿瘤的lsd1抑制剂的组合
KR102528406B1 (ko) 2016-10-27 2023-05-03 셀젠 콴티셀 리서치, 인크. 브로모도메인 및 엑스트라-말단 단백질 억제제 병용 치료요법
US20180133212A1 (en) * 2016-11-03 2018-05-17 Gilead Sciences, Inc. Combination of a bcl-2 inhibitor and a bromodomain inhibitor for treating cancer
WO2018094275A1 (en) 2016-11-18 2018-05-24 Tolero Pharmaceuticals, Inc. Alvocidib prodrugs and their use as protein kinase inhibitors
WO2018106988A1 (en) * 2016-12-09 2018-06-14 Smet Pharmaceutical Inc. Biologically active compositions containing two different classes of chemical compounds for treating solid tumors
KR20190099260A (ko) 2016-12-19 2019-08-26 톨레로 파마수티컬스, 인크. 프로파일링 펩티드 및 감도 프로파일링을 위한 방법
ES2928773T3 (es) 2017-01-17 2022-11-22 Heparegenix Gmbh Inhibidores de proteína cinasas para fomentar la regeneración hepática o reducir o prevenir la muerte de hepatocitos
CN110891608A (zh) * 2017-07-26 2020-03-17 豪夫迈·罗氏有限公司 用BET抑制剂和Bcl-2抑制剂进行的组合疗法
EP3664807B1 (en) 2017-08-09 2025-11-19 Mayo Foundation for Medical Education and Research Methods and materials for identifying and treating bet inhibitor-resistant cancers
WO2019055579A1 (en) 2017-09-12 2019-03-21 Tolero Pharmaceuticals, Inc. TREATMENT REGIME FOR CANCERS THAT ARE INSENSITIVE TO BCL-2 INHIBITORS USING THE MCL-1 ALVOCIDIB INHIBITOR
KR102141697B1 (ko) * 2017-11-23 2020-08-05 한국과학기술원 PI3K/mTOR 저해제 저항성 암 치료제
US20190240198A1 (en) * 2018-02-05 2019-08-08 Dean G. Tang Formulations and methods for the treatment of cancers
EP3758753A1 (en) * 2018-02-27 2021-01-06 Pfizer Inc Combination of a cyclin dependent kinase inhibitor and a bet-bromodomain inhibitor
CZ308400B6 (cs) * 2018-04-11 2020-07-29 Univerzita Karlova Farmaceutický přípravek pro léčení maligního melanomu
WO2020023768A1 (en) 2018-07-25 2020-01-30 Mayo Foundation For Medical Education And Research Methods and materials for identifying and treating bet inhibitor-resistant cancers
US11034710B2 (en) 2018-12-04 2021-06-15 Sumitomo Dainippon Pharma Oncology, Inc. CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer
US11793802B2 (en) 2019-03-20 2023-10-24 Sumitomo Pharma Oncology, Inc. Treatment of acute myeloid leukemia (AML) with venetoclax failure
CN113018301A (zh) * 2019-12-09 2021-06-25 中国科学院大连化学物理研究所 JQ1与Erlotinib组合物在制备治疗肝癌药物中应用和治疗肝癌药物
CN111012774A (zh) * 2020-03-02 2020-04-17 南通大学附属医院 一种jq-1在制备胰腺癌治疗药物中的应用及其抑制胰腺癌外泌体分泌的验证方法
WO2022111390A1 (zh) * 2020-11-24 2022-06-02 广州君赫生物科技有限公司 化合物在制备调降 runx2 表达试剂中的应用
CN113082037B (zh) * 2021-04-23 2022-09-13 浙江大学 小分子组合物在制备治疗肝内胆管细胞癌药物中的应用
EP4384181A2 (en) * 2021-08-10 2024-06-19 GlaxoSmithKline LLC Momelotinib combination therapy
CN116270683A (zh) * 2022-11-09 2023-06-23 厦门大学 药物组合物在制备抑制人非小细胞肺癌细胞活性的组合物中的应用

Family Cites Families (141)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2951540A (en) 1956-11-05 1960-09-06 Gen Motors Corp Propeller brake
US3709898A (en) 1971-02-09 1973-01-09 Upjohn Co Process for the production of triazolobenzodiazepines and intermediates
US3681343A (en) 1971-05-11 1972-08-01 Upjohn Co 6-phenyl-s-triazolo{8 4,3-a{9 {8 1,4{9 {0 benzodiazepines
US3812259A (en) 1971-08-09 1974-05-21 Upjohn Co Animal feed and process
CH622019A5 (en) 1975-10-23 1981-03-13 Upjohn Co Process for the preparation of aminotriazolobenzodiazepines
FR2329668A1 (fr) 1975-10-27 1977-05-27 Upjohn Co Procede de preparation d'aminotriazolobenzodiazepines
EP0087850A1 (en) 1982-01-04 1983-09-07 The Upjohn Company Benzodiazepines for anti-hypertensive use
DE3435973A1 (de) 1984-10-01 1986-04-10 Boehringer Ingelheim KG, 6507 Ingelheim Diazepine enthaltende pharmazeutische zusammensetzungen mit paf-antagonistischer wirkung
DE3724164A1 (de) 1986-07-25 1988-01-28 Boehringer Ingelheim Kg Neue 1,4-benzodiazepine, ihre herstellung und verwendung
WO1988009333A1 (fr) 1987-05-28 1988-12-01 Yoshitomi Pharmaceutical Industries, Ltd. Compose a base de thieno(triazolo)diazepine et applications medicales de ce compose
JPH0676326B2 (ja) 1988-05-24 1994-09-28 吉富製薬株式会社 循環器系疾患治療薬
EP0368175A1 (de) 1988-11-06 1990-05-16 Boehringer Ingelheim Kg 3S,7S-3-(Morpholinocarbonyl)-5-(2-chlorphenyl)-7,10-dimethyl-3,4-dihydro-2H,7H-cyclopenta[4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin.
EP0387613A1 (de) 1989-03-03 1990-09-19 Boehringer Ingelheim Kg Neue Thienodiazepine
YU133090A (sh) 1989-07-12 1993-10-20 Boehringer Ingelheim Kg. Novi heteroazepini s paf-antaganostičnim učinkom in postopek za njihovo pripravo
DE4010528A1 (de) 1990-04-02 1991-10-17 Boehringer Ingelheim Kg Praeparativ chromatographisches trennverfahren zur herstellung enantiomerenreiner hetrazepine
EP0638560A4 (en) 1991-10-11 1995-03-29 Yoshitomi Pharmaceutical MEDICINE FOR OSTEOPOROSIS AND DIAZEPINE COMPOUND *.
WO1994006802A1 (fr) 1992-09-18 1994-03-31 Yoshitomi Pharmaceutical Industries, Ltd. Compose de thienodiazepine et son utilisation medicinale
CA2159344A1 (en) 1993-03-30 1994-10-13 Minoru Moriwaki Cell adhesion inhibitor and thienotriazolodiazepine compound
WO1995032963A1 (en) 1994-06-01 1995-12-07 Yoshitomi Pharmaceutical Industries, Ltd. Thienylazole compound and thienotriazolodiazepine compound
PT801651E (pt) 1995-01-06 2001-12-28 Hoffmann La Roche Hidroximetil-imidazodiazepinas e seus esteres
US5730723A (en) 1995-10-10 1998-03-24 Visionary Medical Products Corporation, Inc. Gas pressured needle-less injection device and method
DK0853480T3 (da) 1995-09-09 2003-05-05 Hoffmann La Roche Anvendelse af en thienotriazolodiazepin til forøgelse af apolipoprotein A-I-niveauer
GB9607549D0 (en) 1996-04-11 1996-06-12 Weston Medical Ltd Spring-powered dispensing device
PL330635A1 (en) 1996-06-12 1999-05-24 Japan Tobacco Inc Inhibitor of cytokin production, triazepin compound and intermediate compounds used for obtaining the last mentioned one
US5693641A (en) 1996-08-16 1997-12-02 Berlex Laboratories Inc. Bicyclic pyrimidine derivatives and their use as anti-coagulants
DE69717160T2 (de) 1996-09-13 2003-05-08 Mitsubishi Pharma Corp., Osaka Thienotriazolodiazepinverbindungen und ihre medizinischen anwendungen
US6444664B1 (en) 1997-04-18 2002-09-03 Nederlandse Organisatie Voor Toegepast - Natuurweten Schappelijk Onderzoek (Tno) Method for controlling the plasma level of lipoproteins to treat alzheimeris disease
JPH11228576A (ja) 1997-12-10 1999-08-24 Japan Tobacco Inc アポトーシス抑制剤
IT1298087B1 (it) 1998-01-08 1999-12-20 Fiderm S R L Dispositivo per il controllo della profondita' di penetrazione di un ago, in particolare applicabile ad una siringa per iniezioni
FR2779652B1 (fr) 1998-06-15 2001-06-08 Sod Conseils Rech Applic Utilisation de diazepines pour la preparation de medicaments destines a traiter les etats pathologiques ou les maladies dans lesquels un des recepteurs de la somatostatine est implique
KR20000016732A (en) 1998-12-12 2000-03-25 Japan Tobacco Inc Cytokine production inhibitors, triazepine compounds, and intermediates thereof
HK1047236A1 (zh) 1999-05-14 2003-02-14 Imclone Llc 用表皮生长因子受体拮抗剂治疗难治的人肿瘤
US6312215B1 (en) 2000-02-15 2001-11-06 United Technologies Corporation Turbine engine windmilling brake
US7589167B2 (en) 2000-02-22 2009-09-15 J. David Gladstone Institutes ZA loops of bromodomains
WO2001095912A1 (fr) 2000-06-16 2001-12-20 Mitsubishi Pharma Corporation Compositions permettant de reguler la plage et/ou la vitesse de liberation du ph
AU2001270297A1 (en) 2000-06-30 2002-01-14 Neurogen Corporation 2-phenylimidazo(1,2-a)pyridine derivatives: a new class of gaba brain receptor ligands
US20060142257A1 (en) 2001-01-19 2006-06-29 Eberhard Nieschlag Male contraceptive formulation comprising norethisterone
US6979682B2 (en) 2001-02-23 2005-12-27 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Platelet-activating factor antagonist inhibition of angiogenesis and tumor growth induced by basic fibroblast
US20030216758A1 (en) 2001-12-28 2003-11-20 Angiotech Pharmaceuticals, Inc. Coated surgical patches
GB0206215D0 (en) 2002-03-15 2002-05-01 Novartis Ag Organic compounds
US6861422B2 (en) 2003-02-26 2005-03-01 Boehringer Ingelheim Pharma Gmbh & Co. Kg Dihydropteridinones, processes for preparing them and their use as pharmaceutical compositions
ES2545666T3 (es) 2003-02-27 2015-09-14 Abbvie Inc. 5,10-Dihidro-11H-dibenzo[b,e][1,4]diazepin-11-ona como inhibidores de quinasa
GB0305929D0 (en) 2003-03-14 2003-04-23 Novartis Ag Organic compounds
CA2527957A1 (en) 2003-06-02 2005-01-06 Ohio University Use of genes differentially expressed during aging of liver for treatment and diagnosis
WO2005002526A2 (en) 2003-07-01 2005-01-13 President And Fellows Of Harvard College Method and compositions for treatment of viral infections
MXPA06003054A (es) 2003-09-18 2006-05-31 Novartis Ag 2,4-di-(fenil-amino)-pirimidinas utiles en el tratamiento de trastornos proliferativos.
EP1528056A1 (en) 2003-10-29 2005-05-04 Academisch Ziekenhuis bij de Universiteit van Amsterdam Deoxynojirimycin analogues and their uses as glucosylceramidase inhibitors
US20060058311A1 (en) 2004-08-14 2006-03-16 Boehringer Ingelheim International Gmbh Combinations for the treatment of diseases involving cell proliferation
US20060074088A1 (en) 2004-08-14 2006-04-06 Boehringer Ingelheim International Gmbh Dihydropteridinones for the treatment of cancer diseases
US7759485B2 (en) 2004-08-14 2010-07-20 Boehringer Ingelheim International Gmbh Process for the manufacture of dihydropteridinones
US20060035903A1 (en) 2004-08-14 2006-02-16 Boehringer Ingelheim International Gmbh Storage stable perfusion solution for dihydropteridinones
CN1759834B (zh) 2004-09-17 2010-06-23 中国医学科学院医药生物技术研究所 黄连素或其与辛伐他汀联合在制备用于预防或治疗与血脂有关疾病或症状的产品中用途
US8624027B2 (en) 2005-05-12 2014-01-07 Abbvie Inc. Combination therapy for treating cancer and diagnostic assays for use therein
EP1887008B1 (en) 2005-05-30 2021-04-21 Mitsubishi Tanabe Pharma Corporation Thienotriazolodiazepine compound and a medicinal use thereof
WO2007014838A1 (en) 2005-08-03 2007-02-08 Boehringer Ingelheim International Gmbh Dihydropteridinones in the treatment of respiratory diseases
US8133900B2 (en) 2005-11-01 2012-03-13 Targegen, Inc. Use of bi-aryl meta-pyrimidine inhibitors of kinases
CN103626742B (zh) 2005-11-01 2017-04-26 塔格根公司 激酶的联-芳基间-嘧啶抑制剂
US8604042B2 (en) 2005-11-01 2013-12-10 Targegen, Inc. Bi-aryl meta-pyrimidine inhibitors of kinases
WO2007056117A1 (en) 2005-11-04 2007-05-18 Wyeth Antineoplastic combinations of temsirolimus and sunitinib malate
SI1962830T1 (sl) 2005-12-23 2013-07-31 Glaxosmithkline Llc Azaindolni inhibitorji kinaz Aurora
WO2007082806A1 (en) 2006-01-17 2007-07-26 F. Hoffmann-La Roche Ag Aryl-isoxazol-4-yl-imidazo[1,2-a]pyridine useful for the treatment of alzheimer’s disease via gaba receptors
TW200804389A (en) 2006-02-14 2008-01-16 Vertex Pharma Dihydrodiazepines useful as inhibitors of protein kinases
US20070218135A1 (en) 2006-03-14 2007-09-20 Glenmark Pharmaceuticals Limited Sustained release matrix pharmaceutical composition
RU2008147269A (ru) 2006-05-03 2010-06-10 Новартис АГ (CH) Применение органических соединений
US7621117B2 (en) 2006-06-19 2009-11-24 Pratt & Whitney Canada Corp. Apparatus and method for controlling engine windmilling
ATE543819T1 (de) 2006-10-19 2012-02-15 Signal Pharm Llc Heteroarylverbindungen, zusammensetzungen daraus und behandlungsverfahren damit
US8338464B2 (en) 2006-11-30 2012-12-25 Albert Einstein College Of Medicine Of Yeshiva University Small molecule inhibitors of BCL6
JP2008156311A (ja) 2006-12-26 2008-07-10 Institute Of Physical & Chemical Research Brd2ブロモドメイン結合剤
TWI618544B (zh) 2006-12-26 2018-03-21 藍瑟斯醫學影像公司 使心臟神經分布顯像之配位體
WO2008137081A1 (en) 2007-05-02 2008-11-13 The Trustees Of Columbia University In The City Of New York Substituted ( 5, 6 ) -dihydronaphraalenyl compounds as reversible male contraceptives
KR20080107050A (ko) 2007-06-05 2008-12-10 울산대학교 산학협력단 항-cd137 단일클론 항체를 포함하는 만성이식편대숙주 질환의 예방 또는 치료용 약학적 조성물
EP2234986A2 (en) 2007-12-20 2010-10-06 Cellzome Limited Sulfamides as zap-70 inhibitors
WO2009084693A1 (ja) 2007-12-28 2009-07-09 Mitsubishi Tanabe Pharma Corporation 抗癌剤
WO2009112490A1 (en) 2008-03-11 2009-09-17 Cellzome Limited Sulfonamides as zap-70 inhibitors
WO2010015340A1 (en) 2008-08-06 2010-02-11 Bayer Schering Pharma Aktiengesellschaft Daa-pyridine as peripheral benzodiazepine receptor ligand for diagnostic imaging and pharmaceutical treatment
US8569288B2 (en) 2008-10-30 2013-10-29 Circomed Llc Thienotriazolodiazepine derivatives active on apo A
EP2379559B1 (en) 2009-01-06 2017-10-25 Dana-Farber Cancer Institute, Inc. Pyrimido-diazepinone kinase scaffold compounds and methods of treating disorders
KR101779137B1 (ko) 2009-01-23 2017-09-18 다케다 야쿠힌 고교 가부시키가이샤 폴리(adp-리보스)폴리머라제(parp) 억제제
GB0919431D0 (en) 2009-11-05 2009-12-23 Glaxosmithkline Llc Novel compounds
GB0919423D0 (en) 2009-11-05 2009-12-23 Glaxosmithkline Llc Novel compounds
GB0919426D0 (en) 2009-11-05 2009-12-23 Glaxosmithkline Llc Novel compounds
ES2563057T3 (es) 2009-11-05 2016-03-10 Glaxosmithkline Llc Inhibidor de bromodominio de benzodiazepina
GB0919434D0 (en) 2009-11-05 2009-12-23 Glaxosmithkline Llc Novel compounds
RS54645B1 (sr) 2009-11-05 2016-08-31 Glaxosmithkline Llc Benzodiazepin kao inhibitor bromodomena
GB0919432D0 (en) 2009-11-05 2009-12-23 Glaxosmithkline Llc Use
US8862173B2 (en) 2009-12-10 2014-10-14 Motorola Solutions, Inc. Method for selecting media for delivery to users at an incident
EP2536725B1 (en) 2010-02-17 2015-10-28 Boehringer Ingelheim International GmbH Dihydropteridinones, method for production and use thereof
WO2011162845A1 (en) 2010-03-26 2011-12-29 Rolls-Royce North American Technologies, Inc. Adaptive fan system for a variable cycle turbofan engine
MX354217B (es) 2010-05-14 2018-02-19 Dana Farber Cancer Inst Inc Composiciones y metodos para el tratamiento de leucemia.
WO2011143651A1 (en) 2010-05-14 2011-11-17 Dana-Farber Cancer Institute, Inc. Compositions and methods for modulating metabolism
CN103180318B (zh) 2010-05-14 2017-05-10 达那-法伯癌症研究所 雄性避孕组合物以及使用方法
PL2902030T3 (pl) 2010-05-14 2017-07-31 Dana-Farber Cancer Institute, Inc. Związki tienotriazolodiazepinowe do leczenia nowotworu
JP5715241B2 (ja) 2010-05-14 2015-05-07 ダナ−ファーバー キャンサー インスティテュート, インコーポレイテッド 新生物、炎症性疾患、およびその他の障害を治療するための組成物および方法
US9085582B2 (en) 2010-06-22 2015-07-21 Glaxosmithkline Llc Benzotriazolodiazepine compounds inhibitors of bromodomains
NZ605874A (en) 2010-06-25 2015-02-27 Shire Human Genetic Therapies Methods and compositions for cns delivery of heparan n-sulfatase
US20120014979A1 (en) 2010-07-16 2012-01-19 Alexander Dent Use of bcl6 inhibitors for treating autoimmune diseases
TWI583689B (zh) 2010-08-04 2017-05-21 達納 法柏癌症學院有限公司 治療腫瘤形成、發炎疾病及其他病症之組成物及方法
WO2012050907A2 (en) 2010-09-28 2012-04-19 The Regents Of The University Of California Gaba agonists in the treatment of disorders associated with metabolic syndrome and gaba combinations in treatment or prophylaxis of type i diabetes
US9249161B2 (en) 2010-12-02 2016-02-02 Constellation Pharmaceuticals, Inc. Bromodomain inhibitors and uses thereof
AR084070A1 (es) 2010-12-02 2013-04-17 Constellation Pharmaceuticals Inc Inhibidores del bromodominio y usos de los mismos
US20130004481A1 (en) 2011-01-12 2013-01-03 Boehringer Ingelheim International Gmbh Anticancer therapy
EP2677865A4 (en) 2011-02-23 2015-04-22 Icahn School Med Mount Sinai BROMODOMAIN INHIBITORS AS MODULATORS OF GENE EXPRESSION
ES2951688T3 (es) 2011-02-28 2023-10-24 Epizyme Inc Compuestos de heteroarilo biciclico fusionados en 6,5 sustituidos
US20120244209A1 (en) 2011-03-02 2012-09-27 Roth Jack A Tusc2 therapies
JP2014524409A (ja) 2011-07-29 2014-09-22 ザ・チルドレンズ・ホスピタル・オブ・フィラデルフィア Hivの治療のための組成物および方法
FI20110279A7 (fi) 2011-08-29 2013-03-01 Outotec Oyj Menetelmä metallien talteenottamiseksi niitä sisältävästä materiaalista
WO2013033269A1 (en) 2011-08-29 2013-03-07 Coferon, Inc. Bioorthogonal monomers capable of dimerizing and targeting bromodomains and methods of using same
WO2013033270A2 (en) 2011-08-29 2013-03-07 Coferon, Inc. Bromodomain ligands capable of dimerizing in an aqueous solution, and methods of using same
WO2013033420A1 (en) * 2011-08-30 2013-03-07 Whitehead Institute For Biomedical Research Methods of downregulating translocated oncogene expression using bromodomain inhibitors
DE102011082013A1 (de) 2011-09-01 2013-03-07 Bayer Pharma AG 6H-Thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine
WO2013097052A1 (en) 2011-12-30 2013-07-04 Abbott Laboratories Bromodomain inhibitors
US20130280332A1 (en) 2012-02-17 2013-10-24 Nexbio, Inc. Methods, Compounds and Compositions for Treatment of Influenza and Parainfluenza Patients
WO2013148197A1 (en) 2012-03-28 2013-10-03 The J. David Gladstone Institutes Compositions and methods for reactivating latent immunodeficiency virus
US9763956B2 (en) * 2012-06-19 2017-09-19 The Broad Institute, Inc. Diagnostic and treatment methods in subjects having or at risk of developing resistance to cancer therapy
CN104968334B (zh) 2012-09-28 2018-09-14 翁科埃斯克斯有限公司 包含噻吩并三唑并二氮杂卓化合物的药物制剂
US9567301B2 (en) 2012-11-02 2017-02-14 Dana-Farber Cancer Institute, Inc. Pyrrol-1-yl benzoic acid derivatives useful as myc inhibitors
EP2958923A1 (de) 2013-02-22 2015-12-30 Bayer Pharma Aktiengesellschaft 4-substituierte pyrrolo- und pyrazolo-diazepine
US20160009725A1 (en) 2013-02-22 2016-01-14 Bayer Pharma Aktiengesellschaft Pyrrolo- and pyrazolo-triazolodiazepines as bet-protein inhibitors for treating hyperproliferative diseases
AU2014223990A1 (en) 2013-02-28 2015-09-10 Washington University Methods of treatment of human cytomegalovirus infection and diseases with bromodomain inhibitors
US9714946B2 (en) 2013-03-14 2017-07-25 Dana-Farber Cancer Institute, Inc. Bromodomain binding reagents and uses thereof
JP2016519672A (ja) 2013-03-15 2016-07-07 ジェネンテック, インコーポレイテッド ブロモドメイン含有タンパク質brd7およびbrd9の阻害によるth2媒介性疾患の治療
JP2016520130A (ja) 2013-05-28 2016-07-11 ダナ−ファーバー キャンサー インスティテュート, インコーポレイテッド 心臓疾患における新規治療戦略としてのbet阻害
AU2014292888B2 (en) 2013-07-25 2018-03-22 Dana-Farber Cancer Institute, Inc. Inhibitors of transcription factors and uses thereof
KR20160037201A (ko) 2013-08-06 2016-04-05 온코에틱스 게엠베하 Bet-브로모도메인 억제제를 사용한 미만성 거대 b-세포 림프종 (dlbcl)의 치료 방법
WO2015018522A1 (en) 2013-08-06 2015-02-12 Oncoethix Sa Bet-bromodomain inhibitor shows synergism with several anti-cancer agents in pre-clinical models of diffuse large b-cell lymphoma (dlbcl)
EP3033423A4 (en) 2013-08-16 2017-04-26 Rana Therapeutics Inc. Epigenetic regulators of frataxin
US8988212B2 (en) 2013-08-22 2015-03-24 GM Global Technology Operations LLC Electric vehicle pedestrian warning system
CA2922503C (en) 2013-09-19 2021-10-26 Dana-Farber Cancer Institute, Inc. Methods of bh3 profiling
MX2016004570A (es) 2013-10-11 2016-09-08 Genentech Inc Uso de inhibidores del bromodominio de cbp/ep300 para la inmunoterapia del cáncer.
CA2929652A1 (en) 2013-11-08 2015-05-14 Dana-Farber Cancer Institute, Inc. Combination therapy for cancer using bromodomain and extra-terminal (bet) protein inhibitors
US20160256458A1 (en) 2013-11-18 2016-09-08 Forma Therapeutics, Inc. Benzopiperazine compositions as bet bromodomain inhibitors
WO2015081284A1 (en) 2013-11-26 2015-06-04 Coferon, Inc. Bivalent bromodomain ligands, and methods of using same
ES2857848T3 (es) 2013-12-24 2021-09-29 Bristol Myers Squibb Co Compuestos tricíclicos como agentes antineoplásicos
BR112016017045A2 (pt) 2014-01-31 2017-08-08 Dana Farber Cancer Inst Inc Derivados de diazepano e usos dos mesmos
WO2015117087A1 (en) 2014-01-31 2015-08-06 Dana-Farber Cancer Institute, Inc. Uses of diazepane derivatives
CA2936865A1 (en) 2014-01-31 2015-08-06 Dana-Farber Cancer Institute, Inc. Diaminopyrimidine benzenesulfone derivatives and uses thereof
SG11201607108XA (en) 2014-02-28 2016-09-29 Tensha Therapeutics Inc Treatment of conditions associated with hyperinsulinaemia
BR112017008714A2 (pt) 2014-10-27 2017-12-19 Tensha Therapeutics Inc inibidores de bromodomínio
CA2969417A1 (en) * 2014-12-05 2016-06-09 H. Lee Moffitt Cancer Center And Research Institute, Inc. Bromodomain inhibitor as adjuvant in cancer immunotherapy
CA2989313A1 (en) 2015-06-26 2016-12-29 Tensha Therapeutics, Inc. Treatment of nut midline carcinoma
BR112018006689A2 (pt) 2015-10-02 2018-10-09 Dana Farber Cancer Inst Inc terapia de combinação de inibidores de bromodomínio e bloqueio de ponto de controle

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