ES2521676T3 - Nuevos agentes inhibidores de la proliferación y de la activación de transductores de señales y activadores de la transcripción (STATS) - Google Patents

Nuevos agentes inhibidores de la proliferación y de la activación de transductores de señales y activadores de la transcripción (STATS) Download PDF

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ES2521676T3
ES2521676T3 ES09794969.7T ES09794969T ES2521676T3 ES 2521676 T3 ES2521676 T3 ES 2521676T3 ES 09794969 T ES09794969 T ES 09794969T ES 2521676 T3 ES2521676 T3 ES 2521676T3
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stat3
stats
signal transducers
proliferation inhibitor
transcription activators
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Waldemar Priebe
Stanislaw Skora
Timothy Madden
Izabela Fokt
Charles Conrad
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
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    • C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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Abstract

Un compuesto que tiene una fórmula estructural seleccionada entre el conjunto que consiste en:**Fórmula**

Description

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E09794969
28-10-2014
Tabla 1 Activación de los STATs en cánceres humanos
Tipo de tumor
STAT activado
Tumores de la sangre
Mieloma múltiple
STAT1 , STAT3
Leucemias: Dependientes del HTLV-1 Eritroleucemia Leucemia mielógena aguda (AML) Leucemia mielógena crónica (CML) Leucemia linfocítica granular grande (LGL)
STAT3, STAT5 STAT1, STAT5 STAT1 , STAT3, STAT5 STAT5 STAT3
Linfomas: Relacionado con el EBV/ de Burkitt Micosis fungoide Linfoma de células T cutáneas Linfoma no de Hodgkins (NHL) Linfoma anaplásico de células grandes (ALCL)
STAT3 STAT3 STAT3 STAT3 STAT3
Tumores sólidos
Cáncer de mama
STAT1 , STAT3, STAT5
Cáncer de cabeza y cuello
STAT1 , STAT3, STAT5
Melanoma
STAT3
Cáncer de ovario
STAT3
Cáncer de pulmones
STAT3
Cáncer pancreático
STAT3
Cáncer de próstata
STAT3
Glioma
STAT3, STAT5
Basándose en las referencias citadas en las REFS 12, 17, EBV, virus de Epstein-Barr; HTLV-1, virus linfotrópico T humano-1.
La familia de proteínas STAT (acrónimo de "signal transducer y activator of transcription" ) incluye unos factores de transcripción que son activados específicamente para regular la transcripción de un gen cuando las células se encuentran con citocinas y con factores de crecimiento. En los mamíferos, hay siete miembros conocidos de la familia de proteínas STAT: STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b y STAT6. Yu, H., Jove, R., The STATS of Cancer -New Molecular Targets Come of Age [Los STATS de cáncer – Unas nuevas dianas moleculares alcanzan la madurez de edad], Nature Reviews, 4:97-105 (2004). Estas siete proteínas varían en cuanto a su tamaño entre 750 y 850 aminoácidos. Las proteínas STAT5a y STAT5b, citadas colectivamente en el presente texto como “STAT5”, están íntimamente relacionadas pero son codificadas por diferentes genes. Yu, H., Jove, R, The STATS of Cancer -New Molecular Targets Come of Age, Nature Reviews, 4:97-105 (2004)
Las proteínas STAT actúan como transductores de señales en el citoplasma y como activadores de la transcripción en el núcleo. Kisseleva T., Bhattacharya S., Braunstein J., Schindler C.W., Signaling Through the JAK/STAT Pathway, Recent Advances and Future Challenges [Señalización a través de la ruta de JAK/STAT, recientes avances y futuros retos], Gene 285: 1-24 (2002). Por ejemplo las proteínas STAT transducen a señales procedentes de receptores de citocinas, receptores de factores de crecimiento y tirosina cinasas citoplasmáticas, no de receptores, tales como Src y Abl en el núcleo de una célula, en donde ellas fijan al ADN y regulan la transcripción de un surtido de genes. Id. Como resultado de esto, las proteínas STAT regulan unas funciones fisiológicas, tales como una respuesta inmunitaria, una inflamación, una proliferación, una diferenciación, una supervivencia, una metástasis, una apoptosis y una tolerancia inmunitaria (p.ej. evasión desde el sistema inmunitario de tumores). Xie, T. y colaboradores, Stat3 Activation Regulates the Expression of Matrix Metalloproteinase-2 and Tumor Invasion and Metastasis [La activación de los Stat3 regula la expresión de la metaloproteinasa de matriz -2 y la invasión y metástasis de tumores], Oncogene 23: 3550-3560 (2004); Levy, D.E., Inghirami, G., STAT3: A Multifaceted Oncogene [ STAT3, un oncogén de múltiples facetas] , PNAS 103: 10151-5251-52 (2006).
Los STATs comparten unos dominios conservados estructural y funcionalmente, que incluyen: un dominio terminal de N que refuerza las interacciones entre dímeros de STAT en unos sitios de fijación de ADN adyacentes; un dominio de STAT con una hélice superenrollada, que está implicado en interacciones de una proteína con otra proteína; un dominio de fijación de ADN con un pliegue similar al de la inmunoglobulina para la proteína supresora de tumores p53; un dominio de engarzador similar al de la mano EF, que conecta a los dominios de fijación de ADN y de SH2; un dominio de SH2 que actúa como un conmutador dependiente de la fosforilación para controlar el reconocimiento de receptores y la fijación de ADN; y un dominio de transactivación terminal de C. Chen X., Vinkemeier U., Zhao Y., Jeruzalmi D., Darnell J.E., Kuriyan J., Crystal Structure of a Tyrosine Phosphorylated STAT1 Dimer Bound to DNA [Estructura cristalina de un dímero de STAT-1 fosforilado en tirosina, que está fijado a un ADN] , Cell 93: 827-839 (1998). Con el fin de fijarse a un ADN, las proteínas STAT deben de dimerizarse. Yu, H., Jove, R, The STATS of Cancer -New Molecular Targets Come of Age, Nature Reviews, 4:97105 (2004), Darnell, J.
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Claims (1)

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ES09794969.7T 2008-07-08 2009-06-26 Nuevos agentes inhibidores de la proliferación y de la activación de transductores de señales y activadores de la transcripción (STATS) Active ES2521676T3 (es)

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PCT/US2009/048782 WO2010005807A2 (en) 2008-07-08 2009-06-26 Novel inhibitors of proliferation and activation of signal transducer and activator of transcription (stats)

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Families Citing this family (20)

* Cited by examiner, † Cited by third party
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EP2101819B1 (en) 2006-11-20 2013-01-09 President and Fellows of Harvard College Methods, compositions, and kits for treating pain and pruritis
PL2307367T3 (pl) 2008-07-08 2015-03-31 Univ Texas Nowe inhibitory proliferacji i aktywacji białek przekazujących sygnał i aktywujących transkrypcję (STAT)
CN102725401A (zh) 2009-07-10 2012-10-10 哈佛大学校长及研究员协会 作为抗炎药的永久带电荷的钠和钙通道阻断剂
WO2011069141A2 (en) 2009-12-04 2011-06-09 Board Of Regents, The University Of Texas System Interferon therapies in combination with blockade of stat3 activation
US20110275577A1 (en) * 2010-01-08 2011-11-10 Moleculin, Llc Methods of treating dermatologic, gynecologic, and genital disorders with caffeic acid analogs
RU2689548C2 (ru) * 2012-10-31 2019-05-28 Ионис Фармасьютикалз, Инк. Лечение рака
WO2014085154A1 (en) 2012-11-27 2014-06-05 Beth Israel Deaconess Medical Center, Inc. Methods for treating renal disease
JP6729911B2 (ja) * 2014-09-26 2020-07-29 ナショナル ユニバーシティ オブ シンガポール Ｔｈ−ｇｍ細胞の機能を調節するための方法および組成物
JP6833811B2 (ja) 2015-08-03 2021-02-24 プレジデント アンド フェローズ オブ ハーバード カレッジ 荷電イオンチャネル遮断薬及び使用方法
EP3461916A1 (en) * 2017-10-02 2019-04-03 Koninklijke Philips N.V. Assessment of jak-stat3 cellular signaling pathway activity using mathematical modelling of target gene expression
TW201922707A (zh) * 2017-11-10 2019-06-16 美國德州系統大學評議委員會 咖啡酸衍生物及其用途
JP2022527690A (ja) 2019-03-11 2022-06-03 ノシオン セラピューティクス，インコーポレイテッド 荷電したイオンチャンネル遮断薬および使用方法
US10780083B1 (en) 2019-03-11 2020-09-22 Nocion Therapeutics, Inc. Charged ion channel blockers and methods for use
CN113811305A (zh) 2019-03-11 2021-12-17 诺西恩医疗公司 带电的离子通道阻滞剂及其使用方法
US10828287B2 (en) 2019-03-11 2020-11-10 Nocion Therapeutics, Inc. Charged ion channel blockers and methods for use
CA3129089A1 (en) 2019-03-11 2020-09-17 Bridget Mccarthy Cole Ester substituted ion channel blockers and methods for use
TW202106676A (zh) 2019-04-05 2021-02-16 美商凱麥拉醫療公司 Stat降解劑及其用途
US10933055B1 (en) 2019-11-06 2021-03-02 Nocion Therapeutics, Inc. Charged ion channel blockers and methods for use
WO2021091585A1 (en) 2019-11-06 2021-05-14 Nocion Therapeutics, Inc. Charged ion channel blockers and methods for use
CA3170070A1 (en) 2020-03-11 2021-09-16 Bridget Mccarthy Cole Charged ion channel blockers and methods for use

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL277744A (es) 1961-05-19
DE2555789A1 (de) 1975-12-11 1977-07-07 Hoechst Ag Neue cyanessigsaeureanilid-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende mittel
US6610830B1 (en) 1980-07-01 2003-08-26 Hoffman-La Roche Inc. Microbial production of mature human leukocyte interferons
US4456748A (en) 1981-02-23 1984-06-26 Genentech, Inc. Hybrid human leukocyte interferons
US4414150A (en) 1980-11-10 1983-11-08 Genentech, Inc. Hybrid human leukocyte interferons
US4678751A (en) 1981-09-25 1987-07-07 Genentech, Inc. Hybrid human leukocyte interferons
US6936694B1 (en) 1982-05-06 2005-08-30 Intermune, Inc. Manufacture and expression of large structural genes
DE3410439A1 (de) 1984-03-22 1985-09-26 Hoechst Ag, 6230 Frankfurt Verfahren zur herstellung von 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-on-2,2-dioxid und dessen nichttoxischen salzen sowie der dabei als zwischenprodukt(e) auftretenden acetoacetamind-n-sulfonsaeure(salze)
US4766106A (en) 1985-06-26 1988-08-23 Cetus Corporation Solubilization of proteins for pharmaceutical compositions using polymer conjugation
US4917888A (en) 1985-06-26 1990-04-17 Cetus Corporation Solubilization of immunotoxins for pharmaceutical compositions using polymer conjugation
FR2629455B1 (fr) 1988-03-29 1991-09-27 Rhone Poulenc Agrochimie Derives de 2-(3-pyridinyl)3-(phenoxy) propanenitrile
GB9004483D0 (en) 1990-02-28 1990-04-25 Erba Carlo Spa New aryl-and heteroarylethenylene derivatives and process for their preparation
US5196446A (en) 1990-04-16 1993-03-23 Yissum Research Development Company Of The Hebrew University Of Jerusalem Certain indole compounds which inhibit EGF receptor tyrosine kinase
CA2080582A1 (en) 1990-04-16 1991-10-17 Alfred P. Spada Heterocyclicethenediyl compounds which inhibit egf receptor tyrosine kinase
CA2080554A1 (en) 1991-10-15 1993-04-16 Mitsubishi Chemical Corporation Styrene derivatives
JPH05301838A (ja) 1991-10-15 1993-11-16 Mitsubishi Kasei Corp スチレン誘導体
CA2092017A1 (en) 1992-03-26 1993-09-27 Tameo Iwasaki Butadiene derivatives and process for preparing the same
US5981569A (en) 1992-11-13 1999-11-09 Yissum Research Development Company Of The Hebrew University Of Jerusalem Substituted phenylacrylonitrile compounds and compositions thereof for the treatment of disease
JPH06247850A (ja) 1993-02-24 1994-09-06 Suntory Ltd １２−リポキシゲナーゼ阻害剤
DE4330105A1 (de) 1993-09-06 1995-03-09 Bayer Ag Verwendung von beta-Hetaryl-beta-oxopropionsäurenitrile als Schädlingsbekämpfungsmittel
US5919455A (en) 1993-10-27 1999-07-06 Enzon, Inc. Non-antigenic branched polymer conjugates
US5643575A (en) 1993-10-27 1997-07-01 Enzon, Inc. Non-antigenic branched polymer conjugates
GB9322781D0 (en) 1993-11-04 1993-12-22 Roussel Lab Ltd Aromatic amides
US5951974A (en) 1993-11-10 1999-09-14 Enzon, Inc. Interferon polymer conjugates
HUT75533A (en) 1993-11-10 1997-05-28 Schering Corp Improved interferon polymer conjugates
IL107736A (en) 1993-11-24 2001-01-11 Yissum Res Dev Co Pharmaceutical composition for the prevention of septic shock and for the treatment of chronic inflammatory diseases
IL112205A0 (en) 1994-01-06 1995-03-15 Res Dev Foundation Curcumin, analogues of curcumin and novel uses thereof
US5700823A (en) 1994-01-07 1997-12-23 Sugen, Inc. Treatment of platelet derived growth factor related disorders such as cancers
AU2096895A (en) 1994-03-07 1995-09-25 Sugen, Incorporated Receptor tyrosine kinase inhibitors for inhibiting cell proliferative disorders and compositions thereof
GB9406137D0 (en) 1994-03-28 1994-05-18 Erba Carlo Spa N-substituted beta-aryl- and betaheteroaryl-alpha-cyanoacrylamide derivatives and process for their preparation
AU2360595A (en) 1994-04-22 1995-11-16 Hospital For Sick Children Research and Developement Limited Partnership, The Use of benzylidene-malononitrile derivates for the treatment of leukemia
US5738846A (en) 1994-11-10 1998-04-14 Enzon, Inc. Interferon polymer conjugates and process for preparing the same
US6331555B1 (en) 1995-06-01 2001-12-18 University Of California Treatment of platelet derived growth factor related disorders such as cancers
TW517067B (en) 1996-05-31 2003-01-11 Hoffmann La Roche Interferon conjugates
IL119069A0 (en) 1996-08-14 1996-11-14 Mor Research Applic Ltd Pharmaceutical composition comprising tyrphostins
US20020119129A1 (en) 1997-01-15 2002-08-29 Yeda Research And Development Co. Ltd. Novel IFN receptor 1 binding proteins, DNA encoding them, and methods of modulating cellular response to interferons
DE19707319C1 (de) 1997-02-12 1998-06-18 Mannesmann Ag Verfahren und Einrichtung zum Positionieren der Mündung einer verzehrbaren Lanze
US5854285A (en) 1997-04-03 1998-12-29 Natpro, Inc. Protein kinase inhibitor
US6420338B1 (en) 1997-06-13 2002-07-16 New York University Medical Center Inhibition of the Src kinase family pathway as a method of treating HBV infection and hepatocellular carcinoma
AU737018B2 (en) 1997-07-25 2001-08-09 Tsumura & Co. Pyridylacrylamide derivatives and nephritis remedies and TGF-beta inhibitors containing the same
US6225346B1 (en) 1997-10-24 2001-05-01 Sugen, Inc. Tyrphostin like compounds
EP1086957A4 (en) 1999-03-04 2005-08-31 Riken CATALYST COMPOSITION
US20020045191A1 (en) 2000-09-15 2002-04-18 Schneider Robert J. Inhibition of the SRC kinase family pathway as a method of treating HBV infection and hepatocellular carcinoma
WO2002078617A2 (en) 2001-03-28 2002-10-10 University Of South Florida Materials and methods for treatment of cancer and identification of anti-cancer compounds
JP2003119169A (ja) 2001-07-30 2003-04-23 Shigetoshi Kadota 細胞毒性活性を有する化合物およびそれを有効成分とする医薬組成物
US6433018B1 (en) 2001-08-31 2002-08-13 The Research Foundation Of State University Of New York Method for reducing hypertrophy and ischemia
US7741346B2 (en) 2001-11-30 2010-06-22 Santen Pharmaceutical Co., Ltd. Angiogenesis inhibitor
WO2003068157A2 (en) 2002-02-11 2003-08-21 The Brigham And Women's Hospital, Inc. Kinase inhibitors and methods of use thereof
WO2003073999A2 (en) 2002-03-01 2003-09-12 Pintex Pharmaceuticals, Inc. Pini-modulating compounds and methods of use thereof
EP1495757A1 (en) 2002-04-02 2005-01-12 TSUMURA & CO. Phosphodiesterase iv inhibitor containing pyridylacrylamide derivative
AU2003294441A1 (en) 2002-11-22 2004-06-18 Bristol-Myers Squibb Company 1-aryl-2-hydroxyethyl amides as potassium channel openers
CH696238A5 (de) * 2003-06-30 2007-02-28 Lymphosign Inc Verfahren zur Herstellung von Zimtaldehydverbindungen.
KR20050055479A (ko) 2003-12-08 2005-06-13 김철호 카페인산 또는 카페인산 페네틸에스테르를 유효성분으로하는 ｍｍｐ-9 억제제
EP1701941B1 (en) * 2003-12-11 2012-05-30 Board of Regents, The University of Texas System Compounds for treatment of cell proliferative diseases
JP2007530455A (ja) * 2004-03-26 2007-11-01 エイチエスシー リサーチ アンド ディベロップメント リミテッド パートナーシップ 細胞増殖を調節する化合物
CA2563305A1 (en) 2004-04-09 2005-11-24 University Of South Florida Combination therapies for cancer and proliferative angiopathies
ES2245887B1 (es) 2004-07-02 2007-04-01 Marcos Serrano Gil Rueda de timon plegable para embarcaciones.
US7807719B2 (en) 2004-09-14 2010-10-05 Chaim Roifman Compounds useful for modulating abnormal cell proliferation
JP5264177B2 (ja) 2004-11-22 2013-08-14 アボット・メディカル・オプティクス・インコーポレイテッド 共重合性メチンおよびアントラキノン化合物およびそれらを含有する物品
US7989499B2 (en) 2005-02-09 2011-08-02 Mitotek, Llc Compositions and methods for inhibiting an isoform of human manganese superoxide dismutase
WO2007006143A1 (en) * 2005-07-13 2007-01-18 The Hospital For Sick Children Compositions and methods for detecting transformed cells
CA2641262A1 (en) 2006-02-02 2007-08-16 University Of South Florida Withacnistin compounds for treatment of cancer
RU2456265C2 (ru) 2006-03-31 2012-07-20 Дзе Борд Оф Риджентс Оф Дзе Юниверсити Оф Техас Систем Биологически доступная для перорального применения кофейная кислота, относящаяся к противоопухолевым лекарственным средствам
EP2021496B1 (en) 2006-05-05 2010-08-11 George Mason Intellectual Properties, Inc. Methods for detecting hiv infection
FR2903050B1 (fr) 2006-06-30 2009-02-27 Valeo Systemes Thermiques Dispositif d'eclairage ou de signalisation pour face avant de vehicule automobile et face avant comportant un tel dispositif
US20100292229A1 (en) 2006-06-30 2010-11-18 The Board Of Regents Of The University Of Texas System Tryphostin-analogs for the treatment of cell proliferative diseases
EP2063882A4 (en) 2006-09-05 2010-03-03 Univ Emory TYROSINKINASE INHIBITOR FOR PREVENTING OR TREATING INFECTIONS
WO2008083389A1 (en) 2006-12-29 2008-07-10 Moleculin, L.L.C. Methods of treating skin disorders with caffeic acid analogs
US20080248511A1 (en) 2007-03-26 2008-10-09 Promega Corporation Methods to quench light from optical reactions
US20100144802A1 (en) 2007-03-28 2010-06-10 Heimberger Amy B Small Molecule Inhibitors for Immune Modulation
WO2009009150A2 (en) 2007-07-12 2009-01-15 Renee Michelle Cleary Telecommunication and electronic devices holding apparatus and methods
PL2200431T3 (pl) 2007-09-10 2017-01-31 Boston Biomedical Inc Nowe kompozycje i metody służące leczeniu raka
US20100310563A1 (en) 2007-11-30 2010-12-09 Bumm Thomas G P Methods for treating induced cellular proliferative disorders
CA2709784A1 (en) * 2007-12-21 2009-07-09 University Of Rochester Method for altering the lifespan of eukaryotic organisms
US7989572B2 (en) 2008-01-17 2011-08-02 Eastman Chemical Company Polyvinyl ultraviolet light absorbers for personal care
PL2307367T3 (pl) 2008-07-08 2015-03-31 Univ Texas Nowe inhibitory proliferacji i aktywacji białek przekazujących sygnał i aktywujących transkrypcję (STAT)
US8450337B2 (en) * 2008-09-30 2013-05-28 Moleculin, Llc Methods of treating skin disorders with caffeic acid analogs
US20120021941A1 (en) 2009-01-12 2012-01-26 The Board Of Regents Of The University Of Texas System Blood test for the detection of cancer

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AU2009268841B2 (en) 2014-02-06
NZ590372A (en) 2012-09-28
CN102143947A (zh) 2011-08-03
US8637675B2 (en) 2014-01-28
EP2307367B1 (en) 2014-09-24
CN102143947B (zh) 2015-06-24
JP5675606B2 (ja) 2015-02-25
US20140228414A1 (en) 2014-08-14
WO2010005807A3 (en) 2010-03-25
EA201170160A1 (ru) 2011-08-30
US8143412B2 (en) 2012-03-27
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EA020766B1 (ru) 2015-01-30
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US20110053992A1 (en) 2011-03-03
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