BR112015010504A2 - uso de inibidores de molécula pequena de malt1, método de identificação de um modulador de molécula pequena de malt1, e composição farmacêutica - Google Patents
uso de inibidores de molécula pequena de malt1, método de identificação de um modulador de molécula pequena de malt1, e composição farmacêuticaInfo
- Publication number
- BR112015010504A2 BR112015010504A2 BR112015010504A BR112015010504A BR112015010504A2 BR 112015010504 A2 BR112015010504 A2 BR 112015010504A2 BR 112015010504 A BR112015010504 A BR 112015010504A BR 112015010504 A BR112015010504 A BR 112015010504A BR 112015010504 A2 BR112015010504 A2 BR 112015010504A2
- Authority
- BR
- Brazil
- Prior art keywords
- malt1
- dlbcl
- abc
- activity
- suppression
- Prior art date
Links
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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
- C12Q1/37—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving peptidase or proteinase
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/914—Hydrolases (3)
- G01N2333/948—Hydrolases (3) acting on peptide bonds (3.4)
- G01N2333/95—Proteinases, i.e. endopeptidases (3.4.21-3.4.99)
- G01N2333/964—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue
- G01N2333/96425—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals
- G01N2333/96427—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general
- G01N2333/9643—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general with EC number
- G01N2333/96466—Cysteine endopeptidases (3.4.22)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/04—Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/20—Screening for compounds of potential therapeutic value cell-free systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Analytical Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
abstract malt1 cleavage activity is linked to the pathogenesis of activated b-cell-like diffuse large b-cell lymphoma (abc-dlbcl), a chemo-resistant form of dlbcl. we developed a malt1 activity assay and identified chemically diverse malt1 inhibitors. a selected lead compound mi-2 featured direct binding to malt1 and suppression of its protease function. mi-2 concentrated within human abc-dlbcl cells and irreversibly inhibited cleavage of malt1 substrates. this was accompanied by suppression of nf-?b reporter activity, inhibition of nuclear localization of c-rel and downregulation of nf-?b target gene signature. most notably, mi-2 was non-toxic to mice, and displayed potent and specific activity against abc-dlbcl cell lines in vitro, and xenotransplanted abc-dlbcl tumors in vivo. the compound was also effective against primary human non-gcb-dlbcls ex vivo. ----------------------------------------------------------------------------------------------- tradução do resumo resumo patente de invenção: "inibidores de molécula pequena de malt1". a presente invenção refere-se à atividade de clivagem malt1 que está ligada à patogênese de linfoma de células b ativadas por meio das células b do tipo difuso grandes (abc-dlbcl), uma forma quimio-resistente de dlbcl. foi desenvolvido um ensaio de atividade de malt1 e os diversos inibidores de malt1 quimicamente identificados. um composto de chumbo mi-2 selecionado caracterizou a ligação direta à malt1 e supressão da sua função de protease. mi-2 concentrado no interior das células abc-dlbcl humanas e clivagem irreversível inibida de substratos malt1. isto foi acompanhado por meio da supressão da atividade repórter de nf-kb, a inibição de localização nuclear de c-rel e a regulação negativa da assinatura do gene alvo de nf-kb. mais notavelmente, mi-2 era não-tóxico para os camundongos, e exibiu uma atividade potente e específica contra as linhagens celulares de abc-dlbcl in vitro, e tumores xenotransplantados abc-dlbcl in vivo. o composto também foi eficaz contra seres humanos primários não-gcb-lgcbd ex vivo.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261724650P | 2012-11-09 | 2012-11-09 | |
| PCT/US2013/069141 WO2014074815A1 (en) | 2012-11-09 | 2013-11-08 | Small molecule inhibitors of malt1 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BR112015010504A2 true BR112015010504A2 (pt) | 2017-12-05 |
Family
ID=50685175
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112015010504A BR112015010504A2 (pt) | 2012-11-09 | 2013-11-08 | uso de inibidores de molécula pequena de malt1, método de identificação de um modulador de molécula pequena de malt1, e composição farmacêutica |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US9592223B2 (pt) |
| EP (1) | EP2916656B1 (pt) |
| JP (1) | JP6159814B2 (pt) |
| KR (1) | KR20150093695A (pt) |
| CN (1) | CN105188376B (pt) |
| AU (1) | AU2013342267B2 (pt) |
| BR (1) | BR112015010504A2 (pt) |
| CA (1) | CA2890706A1 (pt) |
| EA (1) | EA201590916A1 (pt) |
| IL (1) | IL238719A0 (pt) |
| MX (1) | MX2015005744A (pt) |
| PH (1) | PH12015501035A1 (pt) |
| SG (1) | SG11201503642YA (pt) |
| WO (1) | WO2014074815A1 (pt) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112015010504A2 (pt) | 2012-11-09 | 2017-12-05 | Univ Cornell | uso de inibidores de molécula pequena de malt1, método de identificação de um modulador de molécula pequena de malt1, e composição farmacêutica |
| EP3341007B1 (en) | 2015-08-28 | 2020-12-23 | Cornell University | Malt1 inhibitors and uses thereof |
| JPWO2017057695A1 (ja) * | 2015-09-30 | 2018-07-19 | 東レ株式会社 | ジフェニルピラゾール誘導体及びその医薬用途 |
| CN107296807B (zh) * | 2016-04-15 | 2020-03-20 | 中国科学院上海生命科学研究院 | Malt1靶向抑制物在制备malt1依赖性肿瘤治疗药物中的应用 |
| AU2017302182B2 (en) | 2016-07-29 | 2021-11-04 | Lupin Limited | Substituted thiazolo-pyridine compounds as MALT1 inhibitors |
| EP3495348A4 (en) * | 2016-07-29 | 2020-01-22 | Toray Industries, Inc. | GUANIDINE DERIVATIVE AND USE THEREOF FOR MEDICAL PURPOSES |
| RU2021113671A (ru) | 2016-07-29 | 2021-07-08 | Люпин Лимитед | Замещенные тиазолопиридиновые соединения в качестве ингибиторов malt1 |
| JPWO2018159650A1 (ja) * | 2017-02-28 | 2019-12-19 | 東レ株式会社 | グアニジン誘導体及びその医薬用途 |
| US11248007B2 (en) | 2017-03-08 | 2022-02-15 | Cornell University | Inhibitors of MALT1 and uses thereof |
| CN107162978B (zh) * | 2017-05-25 | 2019-06-07 | 福州大学 | 一种1,3,5-三取代吡唑化合物及其制备方法和应用 |
| CN107698511B (zh) * | 2017-11-07 | 2020-05-08 | 福州大学 | 一种1,3-二芳基-5-烷氧基吡唑化合物及其制备方法和应用 |
| AU2018395291A1 (en) | 2017-12-28 | 2020-07-30 | The General Hospital Corporation | Targeting the CBM signalosome complex induces regulatory T cells to inflame the tumor microenvironment |
| US20230235077A1 (en) | 2020-06-24 | 2023-07-27 | The General Hospital Corporation | Materials and methods of treating cancer |
| WO2022101676A1 (en) * | 2020-11-12 | 2022-05-19 | Monopteros Therapeutics,Inc. | Materials and methods of treating cancer |
| CN113908279B (zh) * | 2021-11-16 | 2022-12-06 | 四川大学华西医院 | Malt1基因作为标志物在制备治疗结直肠癌药物中的应用 |
| CA3240140A1 (en) * | 2021-12-10 | 2023-06-15 | Rarefied Biosciences, Inc. | Methods for treating diseases using malt1 inhibitors |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4746669A (en) | 1985-12-23 | 1988-05-24 | Merck & Co., Inc. | Substituted thiazoles as immunoregulants |
| JP2002517385A (ja) * | 1998-06-05 | 2002-06-18 | イカゲン インク． | カリウムチャネル阻害剤 |
| DE69936105T3 (de) | 1998-11-13 | 2017-07-27 | Immunex Corporation | Menschliche tslp nukleinsäuren und polypeptide |
| ES2219381T3 (es) | 1999-08-06 | 2004-12-01 | Vertex Pharmaceuticals Incorporated | Inhibidores de caspasa y usos de los mismos. |
| JP2003509501A (ja) * | 1999-09-23 | 2003-03-11 | アストラゼネカ・アクチエボラーグ | 治療薬キナゾリン化合物 |
| AUPR878201A0 (en) | 2001-11-09 | 2001-12-06 | Fujisawa Pharmaceutical Co., Ltd. | New compounds |
| EP1458754B1 (en) | 2001-12-18 | 2009-12-09 | Endocube SAS | Novel death associated proteins of the thap family and related par4 pathways involved in apoptosis control |
| EP1556039A2 (en) * | 2002-10-11 | 2005-07-27 | Bristol-Myers Squibb Company | Process for the preparation of tri-nitrogen containing heteroaryl-diamine derivatives useful as pharmaceutical agents and methods of producing pharmaceutical agents |
| AU2004253478A1 (en) | 2003-06-20 | 2005-01-13 | Nereus Pharmaceuticals, Inc. | Use of [3.2.0] heterocyclic compounds and analogs thereof for the treatment of cancer, inflammation and infectious diseases |
| BRPI0413197A (pt) | 2003-08-01 | 2006-10-03 | Amgen Inc | cristal de eta wercept; método para fabricar um cristal de etanercept; composição; uso de um cristal de etanercept |
| US20080234252A1 (en) | 2005-05-18 | 2008-09-25 | Pfizer Inc | Compounds Useful in Therapy |
| CA2653336C (en) * | 2006-05-25 | 2014-10-28 | Synta Pharmaceuticals Corp. | Method for treating non-hodgkin's lymphoma |
| ATE553769T1 (de) * | 2007-11-21 | 2012-05-15 | Vib Vzw | Inhibitoren der malt1-proteolytischen aktivität und ihre verwendung |
| EP2286808A1 (en) * | 2009-08-18 | 2011-02-23 | Rheinische Friedrich-Wilhelms Universität | Cytohesin inhibitors |
| DE102010013716A1 (de) * | 2010-03-31 | 2011-10-06 | Rheinische Friedrich-Wilhelms-Universität Bonn Körperschaft des öffentlichen Rechts | Verwendung von Cytohesin-Inhibitoren |
| BR112015010504A2 (pt) | 2012-11-09 | 2017-12-05 | Univ Cornell | uso de inibidores de molécula pequena de malt1, método de identificação de um modulador de molécula pequena de malt1, e composição farmacêutica |
-
2013
- 2013-11-08 BR BR112015010504A patent/BR112015010504A2/pt not_active IP Right Cessation
- 2013-11-08 EA EA201590916A patent/EA201590916A1/ru unknown
- 2013-11-08 US US14/439,621 patent/US9592223B2/en active Active
- 2013-11-08 CN CN201380069677.4A patent/CN105188376B/zh not_active Expired - Fee Related
- 2013-11-08 CA CA2890706A patent/CA2890706A1/en not_active Abandoned
- 2013-11-08 SG SG11201503642YA patent/SG11201503642YA/en unknown
- 2013-11-08 EP EP13853142.1A patent/EP2916656B1/en not_active Not-in-force
- 2013-11-08 KR KR1020157015329A patent/KR20150093695A/ko not_active Application Discontinuation
- 2013-11-08 AU AU2013342267A patent/AU2013342267B2/en not_active Ceased
- 2013-11-08 WO PCT/US2013/069141 patent/WO2014074815A1/en active Application Filing
- 2013-11-08 JP JP2015541923A patent/JP6159814B2/ja not_active Expired - Fee Related
- 2013-11-08 MX MX2015005744A patent/MX2015005744A/es unknown
-
2015
- 2015-05-08 PH PH12015501035A patent/PH12015501035A1/en unknown
- 2015-05-10 IL IL238719A patent/IL238719A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MX2015005744A (es) | 2016-02-10 |
| US9592223B2 (en) | 2017-03-14 |
| CA2890706A1 (en) | 2014-05-15 |
| EP2916656A4 (en) | 2016-09-14 |
| CN105188376B (zh) | 2017-12-01 |
| WO2014074815A1 (en) | 2014-05-15 |
| JP6159814B2 (ja) | 2017-07-05 |
| JP2015536990A (ja) | 2015-12-24 |
| KR20150093695A (ko) | 2015-08-18 |
| EA201590916A1 (ru) | 2016-02-29 |
| CN105188376A (zh) | 2015-12-23 |
| EP2916656B1 (en) | 2017-10-25 |
| AU2013342267B2 (en) | 2017-01-12 |
| IL238719A0 (en) | 2015-06-30 |
| US20150297570A1 (en) | 2015-10-22 |
| SG11201503642YA (en) | 2015-06-29 |
| PH12015501035A1 (en) | 2015-08-24 |
| EP2916656A1 (en) | 2015-09-16 |
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Free format text: ANULADA A PUBLICACAO CODIGO 6.6.1 NA RPI NO 2462 DE 13/03/2018 POR TER SIDO INDEVIDA. |
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| B08F | Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette] |
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| B08K | Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette] |
Free format text: EM VIRTUDE DO ARQUIVAMENTO PUBLICADO NA RPI 2539 DE 03-09-2019 E CONSIDERANDO AUSENCIA DE MANIFESTACAO DENTRO DOS PRAZOS LEGAIS, INFORMO QUE CABE SER MANTIDO O ARQUIVAMENTO DO PEDIDO DE PATENTE, CONFORME O DISPOSTO NO ARTIGO 12, DA RESOLUCAO 113/2013. |