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k | Sigma-AldrichPHENProductsApplicationsServicesDocumentsSupportAnalytical ChemistryCell Culture & AnalysisChemistry & BiochemicalsClinical & DiagnosticsFiltrationGreener Alternative ProductsIndustrial MicrobiologyLabwareMaterials ScienceMolecular Biology & Functional GenomicsmRNA Development & ManufacturingPharma & Biopharma ManufacturingProtein BiologyWater PurificationAnalytical ChemistryCell Culture & AnalysisChemistry & Synthesis Clinical & DiagnosticsEnvironmental & Cannabis TestingFood & Beverage Testing & ManufacturingGenomicsMaterials Science & EngineeringMicrobiological TestingmRNA Development & ManufacturingPharma & Biopharma ManufacturingProtein BiologyResearch & Disease AreasContract ManufacturingContract TestingCustom ProductsDigital Solutions for Life ScienceIVD Development & ManufacturingmRNA Development & ManufacturingProduct ServicesSupportSafety Data Sheets (SDS)Certificates of Analysis (COA)Certificates of Origin (COO)Certificates of Quality (COQ)Customer SupportContact UsFAQSafety Data Sheets (SDS)Certificates (COA/COO)Quality & RegulatoryCalculators & AppsWebinarsAdvanced SearchStructure SearchSearch WithinProductsTechnical DocumentsSite ContentPapersGenesChromatogramsProduct Categorybioactive small molecules (17)agonists (1)BrandSigma-Aldrich (17)ColorFormula WeightGene AliasPhysical FormPurityResearch AreaQuality SegmentOptical IsomerAvailable for SalePhilippinesGloballymerckApplied Filters:Keyword:'merck'Showing 1-17 of 17 results for "merck" within ProductsProductsGenesPapersTechnical DocumentsSite ContentChromatogramsFilter & SortAll Photos(1)L-798106Synonym(s): (2E)-N-[(5-bromo-2-methoxyphenyl)sulfonyl]-3-[2-(2-naphthalenylmethyl)phenyl]-2-propenamideEmpirical Formula (Hill Notation): C27H22BrNO4SCAS No.: 244101-02-8Molecular Weight: 536.44CompareProduct No.DescriptionSDSPricingL4545≥98% (HPLC)ExpandHideAll Photos(1)DOV 216,303Synonym(s): (±)-1-(3,4-dichlorophenyl)-3-azabicyclo-[3.1.0]hexane hydrochlorideEmpirical Formula (Hill Notation): C11H11Cl2N · HClCAS No.: 86215-36-3Molecular Weight: 264.58CompareProduct No.DescriptionSDSPricingD6446≥98% (HPLC)ExpandHideAll Photos(1)OPC-21268 hydrateSynonym(s): 1-{1-[4(3-acetylaminopropoxy)benzoyl]-4-piperidyl}-3,4-dihydro-2(1H)-quinolinone hydrate, N-[3-[4-[[4-(3,4-dihydro-2-oxo-1(2H)-quinolinyl)-1-piperidinyl]carbonyl]phenoxy]propyl]-acetamide hydrateEmpirical Formula (Hill Notation): C26H31N3O4 · xH2OCAS No.: 131631-89-5Molecular Weight: 449.54 (anhydrous basis)CompareProduct No.DescriptionSDSPricingO1016≥98% (HPLC)ExpandHideAll Photos(1)Indinavir sulfate salt hydrateSynonym(s): 2,3,5-Trideoxy-N-[(1S,2R)-2,3-dihydro-2-hydroxy-1H-inden-1-yl]-5-[(2S)-2-[[(1,1-dimethylethyl)amino]carbonyl]-4-(3-pyridinylmethyl)-1-piperazinyl]-2-(phenylmethyl)-D-erythro-pentonamide sulfate hydrate, Crixivan hydrate, L-735,524 hydrate, MK-639 hydrateEmpirical Formula (Hill Notation): C36H47N5O4·H2SO4 · xH2OMolecular Weight: 711.87 (anhydrous basis)CompareProduct No.DescriptionSDSPricingSML0189≥98% (HPLC)ExpandHideAll Photos(1)4E1RCatSynonym(s): 4-[(3E)-3-[[5-(4-nitrophenyl)furan-2-yl]methylidene]-2-oxo-5-phenylpyrrol-1-yl]benzoic acidEmpirical Formula (Hill Notation): C28H18N2O6Molecular Weight: 478.45CompareProduct No.DescriptionSDSPricingSML0197≥97% (HPLC)ExpandHideAll Photos(1)XE-991Synonym(s): 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenoneEmpirical Formula (Hill Notation): C26H20N2OCAS No.: 122955-42-4Molecular Weight: 376.45CompareProduct No.DescriptionSDSPricingX2254≥98% (HPLC)ExpandHideAll Photos(1)DevazepideSynonym(s): (S)-N-(2,3-Dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)indole-2-carboxamide, L-364,718, MK 329Empirical Formula (Hill Notation): C25H20N4O2CAS No.: 103420-77-5Molecular Weight: 408.45CompareProduct No.DescriptionSDSPricingD3821≥98% (HPLC), powderExpandHideAll Photos(3)MK-571 sodium salt hydrateSynonym(s): 5-(3-(2-(7-Chloroquinolin-2-yl)ethenyl)phenyl)-8-dimethylcarbamyl-4,6-dithiaoctanoic acid sodium salt hydrate, L-660711Empirical Formula (Hill Notation): C26H26ClN2NaO3S2 · xH2OCAS No.: 115103-85-0Molecular Weight: 537.07 (anhydrous basis)CompareProduct No.DescriptionSDSPricingM7571≥95% (HPLC)ExpandHideAll Photos(1)Montelukast sodium hydrateSynonym(s): 1-[[[(1R)-1-[3-[(1E)-2-(7-Chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid sodium salt hydrateEmpirical Formula (Hill Notation): C35H35ClNO3S·Na · xH2OMolecular Weight: 608.17 (anhydrous basis)CompareProduct No.DescriptionSDSPricingSML0101≥98% (HPLC)ExpandHideAll Photos(1)Enalaprilat dihydrateSynonym(s): (2S)-1-[(2S)-2-[[(1S)-1-Carboxy-3-phenyl-propyl]amino]propanoyl]pyrrolidine-2-carboxylic acid, VasotecEmpirical Formula (Hill Notation): C18H24N2O5 ·2H2OCAS No.: 84680-54-6Molecular Weight: 384.42EC No.: 278-459-3CompareProduct No.DescriptionSDSPricingE9658≥98% (HPLC)ExpandHideAll Photos(1)L-655,708Synonym(s): Ethyl (S)-11,12,13,13a-Tetrahydro-7-methoxy-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate, L-655708Empirical Formula (Hill Notation): C18H19N3O4CAS No.: 130477-52-0Molecular Weight: 341.36CompareProduct No.DescriptionSDSPricingL9787≥98% (HPLC), powderExpandHideAll Photos(1)L-368,899Synonym(s): 1-((7,7-Dimethyl-2(S)-(2(S)-amino-4-(methylsulfonyl)butyramido)bicyclo[2,2,1]heptan-1(S)-yl)methylsulfonyl)-4-(2-methylphenyl)piperazine hydrochlorideEmpirical Formula (Hill Notation): C26H42O5N4S2 · HClMolecular Weight: 591.23CompareProduct No.DescriptionSDSPricingL2540≥98% (HPLC), powderExpandHideAll Photos(1)MMPIPSynonym(s): 6-(4-Methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo[ 4,5-c]pyridin-4(5H)-oneEmpirical Formula (Hill Notation): C19H15N3O3CAS No.: 479077-02-6Molecular Weight: 333.34CompareProduct No.DescriptionSDSPricingM3074≥98% (HPLC)ExpandHideAll Photos(2)SimvastatinEmpirical Formula (Hill Notation): C25H38O5CAS No.: 79902-63-9Molecular Weight: 418.57CompareProduct No.DescriptionSDSPricingS6196≥97% (HPLC), solidExpandHideAll Photos(1)MTEP hydrochlorideSynonym(s): MTEP hydrochloride, 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine hydrochlorideEmpirical Formula (Hill Notation): C11H8N2SHClMolecular Weight: 236.72CompareProduct No.DescriptionSDSPricingM4699≥98% (HPLC)ExpandHideAll Photos(1)Akt1/2 kinase inhibitorSynonym(s): 1,3-Dihydro-1-(1-((4-(6-phenyl-1H-imidazo[4,5-g]quinoxalin-7-yl)phenyl)methyl)-4-piperidinyl)-2H-benzimidazol-2-one trifluoroacetate salt hydrate, Akt Inhibitor VIII trifluoroacetate salt hydrate, Akti-1/2 trifluoroacetate salt hydrateEmpirical Formula (Hill Notation): C34H29N7O · xC2HF3O2 · yH2OMolecular Weight: 551.64 (anhydrous free base basis)CompareProduct No.DescriptionSDSPricingA6730≥98% (HPLC)ExpandHideAll Photos(2)L-685,458Synonym(s): (5S)-(t-Butoxycarbonylamino)-6-phenyl-(4R)hydroxy-(2R)benzylhexanoyl)-L-leu-L-phe-amideEmpirical Formula (Hill Notation): C39H52O6N4CAS No.: 292632-98-5Molecular Weight: 672.85CompareProduct No.DescriptionSDSPricingL1790>96% (HPLC), solidExpandHidePage 1 of 1Page 1 o

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全球知名藥企：默沙東和默克，你還傻傻分不清嗎？ - 知乎

全球知名藥企：默沙東和默克，你還傻傻分不清嗎？ - 知乎首發(fā)于疫苗公司切換模式寫文章登錄/注冊全球知名藥企：默沙東和默克，你還傻傻分不清嗎？e苗君預(yù)約HPV疫苗關(guān)注濟苗通你有沒有發(fā)現(xiàn)：默克和默沙東兩家公司的百科上，英文名字都是Merck，但是中文卻大不相同。這是為什么？其實這里面有一個令人感慨的“血緣”故事，今天苗苗醬就來跟大家分享一下。1668年，一個叫默克（弗雷德里奇·杰考伯·默克）的人收購了位于德國達姆施塔特的天使藥房，開啟了他的創(chuàng)業(yè)之路。發(fā)展到1816年，默克的后代——海因里?！ひ谅~爾·默克接管了天使藥房，但是擁有雄心壯志的他不滿足于現(xiàn)狀，于是開始著手將天使藥房發(fā)展成一個全球化的公司。由于默克公司的全球業(yè)務(wù)開展的非常成功，所以在1891年，默克在美國紐約成立了分公司——Merck& Co.。后來，第一次世界大戰(zhàn)發(fā)生了，默克公司作為一個跨國企業(yè)，不可避免地受到了戰(zhàn)爭的影響，進而喪失了很多海外子公司，其中包括Merck& Co.。1917年，默克位于美國的子公司Merck& Co.因為戰(zhàn)爭被沒收，所以從此默克與Merck& Co.被迫分家了。1953年，默克與費城的Sharp&Dohme公司合并，這也是默沙東名字的由來。自此以后，默克集團作為默克品牌的創(chuàng)立者，擁有默克（Merck）名稱和商標在除北美以外的全球范圍內(nèi)的使用權(quán)，在北美地區(qū)，默克使用“EMD”名稱。Merck & Co.僅在北美地區(qū)擁有“默克”名稱的使用權(quán)，在北美以外地區(qū)必須使用“MSD”或“MSD Sharp & Dohme”、“Merck Sharp & Dohme”。默克和默沙東雖然是一脈相傳，都是做醫(yī)藥行業(yè)起家，但是現(xiàn)在兩家公司的主營業(yè)務(wù)卻不太一樣。默沙東公司主要致力于處方藥、動物保健、治療及控制，以及疫苗等廣泛的醫(yī)療領(lǐng)域，以實現(xiàn)拯救生命、提高全人類健康水平的目標，還將研發(fā)領(lǐng)域擴展到諸如生物制劑等新的領(lǐng)域。默克公司主要致力于創(chuàng)新型制藥、生命科學(xué)以及前沿功能材料技術(shù)，并以技術(shù)為驅(qū)動力，為患者和客戶創(chuàng)造價值。綜上來說，我們打的疫苗、用的處方藥，只要上面標注的是MSD，就是默沙東，如果是Merck，則是默克公司?？吹竭@，你是不是能分清誰是誰了呢？關(guān)于默沙東的故事，苗苗醬就介紹到這里啦。你還想知道哪個醫(yī)藥公司的故事？可以在后臺告訴苗苗醬哦~發(fā)布于 2021-01-29 10:45制藥企業(yè)制藥跨國公司?贊同 43??8 條評論?分享?喜歡?收藏?申請轉(zhuǎn)載?文章被以下專欄收錄疫苗公司全球知名疫苗公

默克_百度百科

度百科網(wǎng)頁新聞貼吧知道網(wǎng)盤圖片視頻地圖文庫資訊采購百科百度首頁登錄注冊進入詞條全站搜索幫助首頁秒懂百科特色百科知識專題加入百科百科團隊權(quán)威合作下載百科APP個人中心收藏查看我的收藏0有用+10默克播報討論上傳視頻藥物貿(mào)易企業(yè)默克是一家科技公司，專注于醫(yī)藥健康、生命科學(xué)和電子科技三大領(lǐng)域， [56]全球超過60,000名員工服務(wù)于默克。從基因編輯技術(shù)和發(fā)現(xiàn)治療具有挑戰(zhàn)性疾病的獨特方法，到實現(xiàn)設(shè)備的智能化——默克無處不在。2021年，默克在66個國家的總銷售額達197億歐元， [57]集團銷售額增長12.3%。 [58]默克家族作為公司的創(chuàng)始者持有默克大部分的股份，除美國和加拿大例外，在全球都叫“默克”，默克的三大領(lǐng)域：醫(yī)藥健康、生命科學(xué)及電子科技在這兩個國家分別稱之為“EMD Serono”、“MilliporeSigma”和“EMD Electronics”。 [62]默克在中國已經(jīng)有89年發(fā)展歷史， [59]第一個分公司最早于1933年在上海成立 [60]。默克在中國有超過4,500名員工，在北京、上海、香港、無錫、蘇州和南通有21個注冊公司。 [61]中國是默克在全球最為重要的戰(zhàn)略國家之一，并且已成為默克的一個全球創(chuàng)新中心 [63]。近些年來，默克在南通的醫(yī)藥健康和生命科學(xué)業(yè)務(wù)以及在上海的電子科技業(yè)務(wù)分別進行有1.7億歐元、8000萬歐元和4400萬歐元的投資。此外，默克還在北京設(shè)立了全球生物制藥研發(fā)中心，在上海設(shè)有顯示材料研發(fā)中心和生命科學(xué)實驗室 [64]，在蘇州設(shè)有光刻材料研發(fā)中心 [65]。默克在上海和廣東分別設(shè)立了兩家中國創(chuàng)新中心 [66]和一個創(chuàng)新基地 [67]。公司名稱默克外文名Merck KGaA成立時間1668年總部地點德國達姆施塔特市經(jīng)營范圍創(chuàng)新型制藥、生命科學(xué)和電子科技等 [21]公司類型獨資公司口號創(chuàng)新引領(lǐng)生活 Living Innovation年營業(yè)額177億美元（2018年） [3]員工數(shù)6 萬人 [20]董事會主席Karl-Ludwig Kley目錄1品牌歷史2榮譽3默克之道4公司業(yè)務(wù)5默克在中國6企業(yè)責任?全球項目?中國項目品牌歷史播報編輯起源于天使藥房的傳奇1668 年，弗雷德里奇·杰考伯·默克（Friedrich Jacob Merck，1621-1678）收購位于達姆施塔特的天使藥房（Engel-Apotheke，英語: Angel Pharmacy），開啟企業(yè)發(fā)展之路，天使藥房也成為之后家族公司的起源。1816年，海因里希·伊曼紐爾·默克（Heinrich Emanuel Merck，1794-1855）接管天使藥房，開始將其發(fā)展成為一個全球化公司。他首度開始工業(yè)化規(guī)模生產(chǎn)。在醫(yī)藥界，他為簡單手工技藝向科技生產(chǎn)的轉(zhuǎn)變奠定了基礎(chǔ)。1827 年，海因里?！ひ谅~爾·默克開始了工業(yè)化的大規(guī)模生產(chǎn)1900年，默克在全球所有大陸地區(qū)擁有分支機構(gòu)或代表1904年，首次列入醫(yī)學(xué)用藥產(chǎn)品；開始了液晶材料的研究1917年，在美國的子公司被沒收，默克與默沙東兩個公司從此獨立1945年，默克損失部分海外分支機構(gòu), 在廢墟中開始重建1971年，繼亞洲、拉丁美洲后，在美國重新設(shè)立子公司“EMD”1995年，建立德國默克集團（Merck KGaA），并正式在法蘭克福證交所上市。24億德國馬克的發(fā)行量在當時的德國創(chuàng)立了最大公開發(fā)行股票量的歷史紀錄2003年，Erbitux?進入靶向癌癥治療領(lǐng)域2007年，默克收購瑞士雪蘭諾，進軍頂尖生物科技領(lǐng)域2010年，默克收購美國密理博，奠定其在全球生命科學(xué)市場的引先地位2012年，默克在全球廣泛開啟“Fit For 2018”轉(zhuǎn)型項目2014年，默克收購安智電子材料，同年，發(fā)起對西格瑪奧德里奇公司的收購2024年，默克宣布將收購Harpoon Therapeutics [74]“默克”品牌的創(chuàng)始者由于在美國出口業(yè)務(wù)的成功開展，默克公司在紐約成立了一個分公司。1891年，默克美國分公司Merck& Co. 正式成立。第一次世界大戰(zhàn)期間默克喪失了很多海外子公司，其中包括Merck & Co.。1917年，Merck& Co.已成為一家獨立的公司。如今這兩家公司雖同名，但并無其它關(guān)聯(lián)。默克集團作為默克品牌的創(chuàng)立者，擁有“默克（Merck）”名稱和商標在全球范圍（除北美地區(qū)外）的使用權(quán)。在北美地區(qū)，默克使用“EMD”名稱，源自達姆施塔特的伊曼紐爾·默克（Emanuel Merck Darmstadt）的首字母縮寫。Merck & Co.僅在北美地區(qū)擁有“默克”名稱的使用權(quán)，在北美以外地區(qū)必須使用“MSD”或“MSD Sharp & Dohme”、“Merck Sharp & Dohme”。默克集團管理團隊默克集團管理團隊 [68]Allan GaborAllan Gabor安高博默克中國總裁兼電子科技業(yè)務(wù)中國區(qū)董事總經(jīng)理 [69]榮譽播報編輯?默克集團被IMD Lombard Odier2009全球家族企業(yè)獎評為“最佳家族企業(yè)”?默克跨部門的創(chuàng)新項目Innospire榮獲“生物信息技術(shù)知識管理最佳實踐獎”?波士頓商業(yè)雜志授予默克密理博業(yè)務(wù)分支“BBJ環(huán)保獎”，嘉獎其回收及循環(huán)再造計劃?SID Display Week認可默克公司和LG Chem公司聯(lián)合開發(fā)的應(yīng)用于高性能3D顯示器的FPR技術(shù)R&D雜志授予默克密理博業(yè)務(wù)分支“R&D100獎項”，嘉獎其Samplicity?過濾系統(tǒng)為2012年度最具影響意義的100項產(chǎn)品 [1]?默克達姆施塔特的創(chuàng)新包裝理念榮獲2012年德國物流協(xié)會“德國物流獎”?默克家族和默克集團以其公司的文化和社會責任榮獲2012年馬丁·路德國際基金會“路德玫瑰”獎項?默克雪蘭諾在《科學(xué)》雜志最佳雇主的評選中連續(xù)三年位于生命科學(xué)公司前10位 [2]2020年5月13日，默克名列2020福布斯全球企業(yè)2000強榜第308位。 [3-4]2021年5月，默克位列“2021福布斯全球企業(yè)2000強”第232位。 [19]2022年12月9日，默克集團以17,550億人民幣位列《2022胡潤世界500強》第29名。 [71]2023年6月，入選福布斯發(fā)布的2023年福布斯全球企業(yè)2000強榜單，位列第73名。 [72]默克之道播報編輯默克文化是默克行為的基石。默克文化：“忠于自我。默克集團始終信奉企業(yè)的成功構(gòu)筑在以人為本的基礎(chǔ)上。該集團的企業(yè)文化讓每個人都彰顯其不同之處。這種文化以相互尊重和強烈的認同感為基礎(chǔ)?！蹦酥酪馕吨袚熑危O(shè)定質(zhì)量標準，繼續(xù)積極地以創(chuàng)新的理念改變未來。價值觀默克的六大價值觀界定了默克的工作方式。默克企業(yè)價值觀包括責任、尊重、誠信、透明、勇氣和成就。勇氣：開啟未來之門。成就：使我們的企業(yè)成功成為可能。責任：決定了我們的企業(yè)作為。尊重：是一切合作的基礎(chǔ)。誠信：是我們的信用保證。透明：使相互信賴成為可能。默克logo公司口號及使命宣言2013年，默克以“創(chuàng)新引領(lǐng)生活 Living Innovation”作為新的標語，意味著該集團會釋放科研的潛力，為客戶提供高質(zhì)量產(chǎn)品；并致力于改善患者和客戶的生活，努力優(yōu)化組織構(gòu)架和流程，提升公司競爭力。全新的口號意味著該集團將“創(chuàng)新”視為企業(yè)不可分割的一部分，以“創(chuàng)新”決定他們是誰、做什么。 [5]工作在默克默克在全球范圍內(nèi)提供卓越的工作以及國際化的職業(yè)發(fā)展機會，并持續(xù)招募優(yōu)秀的畢業(yè)生和經(jīng)驗豐富的職業(yè)人加入團隊。該集團除了招聘、吸引尖端人才外，還為員工提供培訓(xùn)機會。默克在參與總部發(fā)起的全球培訓(xùn)項目的同時，也專門為本地員工建立了學(xué)習(xí)中心，為其員工創(chuàng)造發(fā)揮才能的契機。公司業(yè)務(wù)播報編輯默克旗下三大業(yè)務(wù)領(lǐng)域 [6]醫(yī)藥健康生命科學(xué)高性能材料醫(yī)藥健康生命科學(xué)高性能材料治療，例如，癌癥，多發(fā)性硬化癥以及不孕不育等疾病的處方藥；日常保健或緩解感冒和疼痛癥狀的非處方藥；以及在過敏癥和生物仿制藥領(lǐng)域的創(chuàng)新。為生命科學(xué)行業(yè)提供創(chuàng)新性工具和實驗室用品，使研究和生物技術(shù)生產(chǎn)更容易、更快速、更成功。包羅萬有的特殊化學(xué)制品，如液晶顯示屏、用于涂料和化妝品的效果顏料，或是電子行業(yè)的高新技術(shù)材料。該業(yè)務(wù)領(lǐng)域旗下業(yè)務(wù)默克雪蘭諾消費者健康生物仿制藥阿羅格默克密理博高性能材料默克雪蘭諾業(yè)務(wù)默克雪蘭諾是默克集團旗下的生物制藥業(yè)務(wù)分支。在美國和加拿大以EMD 雪蘭諾的名稱運營。默克雪蘭諾長期致力于發(fā)展?？浦委燁I(lǐng)域業(yè)務(wù)，包括生殖領(lǐng)域、腫瘤領(lǐng)域、心血管領(lǐng)域、外科及急重癥領(lǐng)域、甲狀腺領(lǐng)域、糖尿病領(lǐng)域、其它內(nèi)分泌領(lǐng)域和變態(tài)反應(yīng)性領(lǐng)域。默克雪蘭諾在全球擁有超過16,000名員工，致力于發(fā)現(xiàn)、開發(fā)、制造和銷售處方藥品，這些藥品遠銷150多個國家。 [7]該公司結(jié)合生物技術(shù)和醫(yī)藥化學(xué)方面的專長以及對專注的治療領(lǐng)域的深刻了解，采用靈活的方法尋找最適合的疾病治療藥物。默克雪蘭諾公司開發(fā)和生產(chǎn)上述兩種來源的新分子實體都取得成功，這讓公司在藥物開發(fā)過程中的各個階段，都能充分發(fā)掘生物和化學(xué)領(lǐng)域的藥物開發(fā)的最大潛力。主要產(chǎn)品 [1]腫瘤:腫瘤靶向治療:愛必妥?(轉(zhuǎn)移性結(jié)直腸癌, 頭頸癌)神經(jīng)變性疾病利比?, Novantrone? (多發(fā)性硬化)生殖:在生殖周期每一階段幫助不孕夫婦: 果納芬?,艾澤?, 樂芮?, 思則凱?, 雪諾酮?, Pergoveris?內(nèi)分泌:與HIV相關(guān)的消瘦 (Serostim?)與HIV相關(guān)的脂肪代謝障礙 (Egrifta?)苯丙酮尿癥(科望?)心臟代謝治療:2型糖尿病 (Glucophage? 家族)心血管疾病 (康忻? β -阻滯劑家族)甲狀腺疾病 (優(yōu)甲樂?)消費者健康業(yè)務(wù)消費者健康業(yè)務(wù)分支在全球擁有超過2000名員工，推動研究和創(chuàng)新，以幫助世界各地的消費者過上更好的生活。旗下品牌行銷全球100多個國家。除歐洲市場外，消費者健康業(yè)務(wù)分支在南美和亞洲的新興市場迅速發(fā)展。 [1]主要產(chǎn)品 [1]自我治療藥品骨關(guān)節(jié): 改善骨關(guān)節(jié)靈活性的產(chǎn)品，如Flexagil?, Seven Seas ?, SevenSeas? JointCare, Kytta?日常保健: 維生素和礦物質(zhì),如Bion?3, Multibionta?, Cebion?, Diabion?,婦女和兒童保健:Femibion?, Kidabion? (Haliborange?)咳嗽和感冒: Nasivin?, Sedalmerck?高性能材料業(yè)務(wù)液晶材料液晶材料是高性能材料部門的關(guān)鍵產(chǎn)品，主要應(yīng)用于電視機，筆記本電腦，數(shù)碼相機，手提電話的液晶顯示器和其它高品質(zhì)顯示器。該部門視新的照明和顯示技術(shù)為重點技資領(lǐng)域。效果顏料與化妝品材料默克是珠光顏料的主要供應(yīng)商之一，該公司的珠光顏料先后獲得了400多項專利。該公司的珠光顏料廣泛應(yīng)用于汽車工業(yè)，塑料工業(yè)，印刷工業(yè)以及化妝品工業(yè)等領(lǐng)域。該集團還提供功能性的顏料。 [1]主要產(chǎn)品 [1]顯示材料事業(yè)部:· 液晶顯示材料· 光刻膠顏料和功能性材料事業(yè)部:· 涂料用珠光顏料· 印刷和塑料工業(yè)用珠光顏料· 應(yīng)用于防偽技術(shù)的效果顏料· 食品和藥品用顏料· 功能性材料· 化妝品活性成分和珠光顏料先進技術(shù)事業(yè)部:· 有機發(fā)光二極管（OLED）· 光電伏材料· 照明用材料集成電路材料事業(yè)部:· 用于集成電路生產(chǎn)的電介質(zhì)、二氧化硅、平版印刷、增產(chǎn)劑、邊緣光刻膠去除劑以及其他配套產(chǎn)品默克密理博業(yè)務(wù)默克集團旗下的默克密理博業(yè)務(wù)，為全球生命科學(xué)用戶提供完整的產(chǎn)品線和強大的創(chuàng)新能力。默克密理博擁有4萬多種產(chǎn)品，是生命科學(xué)行業(yè)三大供應(yīng)商之一。該部門由三個事業(yè)部組成：生命科學(xué)部、實驗室解決方案部和過程工藝解決方案部。 [1]主要產(chǎn)品 [1]生物科學(xué):提供制藥和生物科學(xué)領(lǐng)域研究所需的產(chǎn)品提供蛋白質(zhì)和細胞生物學(xué)研究所需括儀器，耗材和試劑等產(chǎn)品和服務(wù)實驗室解決方案:研發(fā)、科研及工業(yè)實驗室所需的化學(xué)品及相關(guān)材料制藥、食品和診斷行業(yè)取樣及檢測平臺所需的產(chǎn)品和服務(wù)科研和工業(yè)實驗室超純水制備所需的產(chǎn)品、耗材和服務(wù)過程工藝解決方案:為制藥和生物制藥生產(chǎn)企業(yè)提供相關(guān)產(chǎn)品與服務(wù)默克在中國播報編輯1897年，默克開展了中國的業(yè)務(wù)，通過上海、廣州、天津等口岸向中國銷售高純度的化學(xué)試劑。默克公司在中國主要發(fā)達城市北京、上海、廣州、香港都有分公司或代表處。隨著經(jīng)濟持續(xù)增長，中國已經(jīng)成為世界關(guān)注的焦點和最受歡迎的外資投放市場。對于默克，這也意味著絕佳機遇。默克公司依靠其優(yōu)秀員工作為自身價值理念的推動者，依托高科技的創(chuàng)新產(chǎn)品積極參與蓬勃發(fā)展的中國市場，把提升人類生活品質(zhì)作為貫穿始終的理念。 [8]2013年，默克在上海新建的中國液晶中心開業(yè)，投資額達數(shù)千萬歐元，整合了液晶混合生產(chǎn)、研發(fā)和營銷等功能，為本地客戶提供更為便捷和量身定制的服務(wù)。2014年7月23日，跨國制藥與化工企業(yè)默克集團在上海重申投資中國市場，進一步加強中國在其新興市場戰(zhàn)略中的重要性，并宣布其在南通投資6.5億元人民幣新建的制藥廠于8月份破土動工。 [9]新工廠預(yù)計2016年竣工，2017年正式投產(chǎn)，成為默克集團全球第二大制藥廠。該廠主要用于批量生產(chǎn)和包裝治療糖尿病、心血管疾病和甲狀腺功能失調(diào)的格華止、康忻和優(yōu)甲樂產(chǎn)品。這些產(chǎn)品均被納入了國家基本藥物目錄，這使默克成為首家也是唯一在華大規(guī)模新設(shè)投資生產(chǎn)基藥目錄中藥物的跨國藥企。 [9]除了投資藥物生產(chǎn)，默克也拓展了其為生物醫(yī)藥研發(fā)客戶的服務(wù)。默克密理博生命科學(xué)事業(yè)部近期的投資包括在上海張江高科技園區(qū)設(shè)立的生物制藥技術(shù)培訓(xùn)中心，該中心可謂中國市場生物制藥客戶提供技術(shù)支持、培訓(xùn)、驗證等全方位服務(wù)。 [9]默克在中國的歷史1888年，德國化學(xué)家、默克工廠運營主威利·默克（Willy Merck）來到中國；1931年，上海的Schmidt公司成為默克公司在華南地區(qū)的商業(yè)代理。 [22]1933年，怡·默克化工有限公司在上海成立。 [70]2009年，默克建立北京生物制藥中國研發(fā)中心。 [23]2011年，默克在上海設(shè)立液晶應(yīng)用實驗室。 [24]2013年3月，默克雪蘭諾宣布與百時美施貴寶攜手開展格華止?戰(zhàn)略合作； [10]2013年，默克液晶中心在上海成立。 [25]2013年12月，默克液晶中國中心在上海金橋正式開業(yè)，為中國提供中國制造的高品質(zhì)液晶 [11]2014年5月，默克成功收購安智電子材料，包括其在上海的子公司與在蘇州的工廠 [12]2014年，默克制藥工廠在江蘇南通動工。 [26]2016年，默克南通制藥工廠落成， [27]默克南通生命科學(xué)中心一期項目啟動 [28]；默克顯示材料研發(fā)中心在上海開業(yè)。 [29]2017年，默克顏料與功能性技術(shù)應(yīng)用中國中心在上海成立 [30]；默克End-to-End生物工藝開發(fā)中心在中國開業(yè) [31]；默克光刻材料研發(fā)中國中心在蘇州成立。 [32]2018年，默克迎來350周年慶典 [33]2018年2月，默克宣布設(shè)立中國創(chuàng)新中心 [34]2018年6月，OLED技術(shù)中心投入運營 [35]2018年7月，默克宣布與西安楊森合作共同推出2型糖尿病新藥 [36]2018年9月，中國首個Mobius?一次性技術(shù)產(chǎn)品生產(chǎn)基地在無錫成立 [37]2018年12月，默克SAFC?上游技術(shù)研發(fā)中心在上海啟用 [38]2019年5月，默克上海辦公室喬遷 [39]2019年9月，默克攜手阿里巴巴設(shè)立官方旗艦店 [40]并完成對Intermolecular公司的收購 [41]2019年10月，默克中國創(chuàng)新中心在上海正式開幕默克中國種子基金設(shè)立 [42]；默克完成對Versum公司的收購 [43]2019年11月，默克廣東創(chuàng)新中心正式開幕 [44]2020年3月，默克醫(yī)藥經(jīng)營（江蘇）有限公司正式投入運營 [45]2020年5月，默克生命科學(xué)成都配送中心正式啟用 [46]2020年7月，默克生命科學(xué)技術(shù)與培訓(xùn)中心在上海啟用 [47]2020年11月，默克正式啟用中文品牌標志 [48]2021年3月，默克旗下高性能材料業(yè)務(wù)正式更名為默克電子科技 [49]2021年7月，默克攜生命科學(xué)、電子科技和創(chuàng)新中心相關(guān)的產(chǎn)品和解決方案亮相2021世界人工智能大會 [50]2021年10月，默克抗高血壓新型藥物比索洛爾氨氯地平片在中國正式上市 [51]2021年10月，默克與生物谷（北京）科技有限公司合作打造生物科技公共研發(fā)平臺 [52]2021年10月，默克默克上海創(chuàng)新基地在浦東張江投入運營。上海創(chuàng)新基地占地面積2000平方米，是默克在全球建立的首個面向初創(chuàng)企業(yè)開放的創(chuàng)新平臺。 [53]2023年12月8日，默克宣布，中國國家藥品監(jiān)督管理局正式批準拓得康?（鹽酸特泊替尼片）用于治療攜帶間質(zhì)上皮轉(zhuǎn)化因子（MET）外顯子14跳躍突變的局部晚期或轉(zhuǎn)移性非小細胞肺癌（NSCLC）成人患者。 [73]默克在華八十周年2013年，默克中國迎來了八十周年華誕。默克在華的兩大業(yè)務(wù)分支默克雪蘭諾及默克化工紛紛通過一系列慶?；顒庸操R默克八十華彩。默克在華八十周年以“八十華彩歷久彌新”為主題，展現(xiàn)該集團在華八十年的歷史、成就和貢獻，并表達了集團對未來的暢想：默克追求創(chuàng)新的腳步永不停歇。默克在華八十周年慶典，既是對歷史的回顧與致敬，更是面向未來的展望與邁進。該集團正積極參與著蓬勃發(fā)展的中國市場，與2,000多名優(yōu)秀員工一起攜手為中國提供品質(zhì)卓越的高科技創(chuàng)新產(chǎn)品。該集團旗下的兩大分支－默克化工與默克雪蘭諾繼續(xù)齊心協(xié)力，與中國市場共同騰飛。默克雪蘭諾中國在中國，默克雪蘭諾擁有員工超過1000人，業(yè)務(wù)遍及全國，在中國主要經(jīng)營8大領(lǐng)域14種藥品。默克雪蘭諾在生殖和甲狀腺治療領(lǐng)域首屈一指，在心血管、內(nèi)分泌、腫瘤 [1]以及糖尿病領(lǐng)域也處于行業(yè)領(lǐng)先地位。 [13]研發(fā)創(chuàng)新2009年11月23日，默克雪蘭諾中國研發(fā)中心在北京成立 [1]，占地總面積1,000余平方米，也是該集團全球的四大研發(fā)中心之一，該配有先進的生物醫(yī)學(xué)科研儀器設(shè)備、數(shù)據(jù)庫等科技資源信息科技能力。除北京外，中國研發(fā)心中心在廣州和上海也有員工。默克中國研發(fā)中心注重與國內(nèi)知名的科學(xué)家、臨床專家充分的學(xué)術(shù)交流。2009年至2011年間，默克雪蘭諾投資600萬人民幣用以支持開展中國生物制品技術(shù)管理人力資源合作項目。 [2]主要產(chǎn)品（國內(nèi)） [1]治療不孕癥的果納芬?生殖產(chǎn)品樂芮?、艾澤?、思則凱?和雪諾同?抗腫瘤藥愛必妥?抗高血壓藥物康忻?治療心絞痛藥物喜格邁?治療消化道急癥的藥物思他寧?治療甲狀腺功能減退癥的優(yōu)甲樂?及治療甲狀腺功能亢進癥的賽治?治療糖尿病的藥物格華止?BH4缺乏癥替代治療用藥科望?抗過敏藥物阿羅格?治療攜帶間質(zhì)上皮轉(zhuǎn)化因子拓得康?默克化工中國默克化工隸屬于默克集團，自1933年，在上海開設(shè)了第一家中國子公司，趙賦斯默克化工中國董事總經(jīng)理經(jīng)過80年的發(fā)展，現(xiàn)已擁有六家子公司業(yè)務(wù)覆蓋全國十八個城市，員工超過700名。在1998年默克化工便成立了默克珠光顏料與化妝品應(yīng)用實驗室。2007年效果顏料實驗室遷址至松江基地，并更名為客戶技術(shù)支持中心，實現(xiàn)了對默克化工旗下所有產(chǎn)品提供技術(shù)支持服務(wù)。除了先進的技術(shù)設(shè)備之外，那里還集中了一大批專業(yè)技術(shù)人員?？蛻艏夹g(shù)支持中心在默克化工中國乃至默克全球的業(yè)務(wù)發(fā)展中都發(fā)揮著至關(guān)重要的作用。 [14]2011年，默克以100%的股份全額收購北京清大天一科技有限公司。北京清大天一科技有限公司是中國生物制藥行業(yè)領(lǐng)先的細胞培養(yǎng)基產(chǎn)品和相關(guān)技術(shù)服務(wù)以及生物反應(yīng)器的供應(yīng)商。收購清大天一后，默克密理博的過程解決方案部門能夠支持中國客戶進行安全、有效的生物醫(yī)藥制造。默克化工主要生產(chǎn)效果顏料產(chǎn)品、實驗室分析試劑、液晶材料等。消費者常見的液晶電視、筆記本電腦、手機顯示屏、化妝品原料的IR3535驅(qū)蚊劑等都是出自該公司。 [1]2024年2月2日，默克宣布旗下肺癌靶向藥物拓得康?（鹽酸特泊替尼片）在中國商業(yè)化上市，正式向全國各家醫(yī)院和藥房供藥。 [75]企業(yè)責任播報編輯全球項目2007年，默克集團與世界衛(wèi)生組織合作共同抵抗非洲學(xué)校兒童感染的血吸蟲病。血吸蟲病是非洲最普遍的僅次于瘧疾的熱帶疾病，感染群體主要為兒童。在此項合作中，默克十年以來一共捐贈含活性吡喹酮的Cesol?600藥品達2億片之多，總價值約8千萬美元，可供兩千七百萬兒童的治療使用。默克獨家支持“全球醫(yī)藥健康基金會”，該項目旨在推廣并使用默克的Minilab，遏制假藥在全球范圍內(nèi)的傳播。默克的移動實驗室可迅速對藥物進行測試，現(xiàn)已有570個類似的實驗室在余80個國家投入使用。此外，默克還積極促進文化交流，支持助公司音樂大使德國默克愛樂樂團，定期在歐洲、亞洲和和拉丁美洲進行巡回演出。中國項目在中國，默克在取得商業(yè)成功的同時積極履行企業(yè)社會責任，開展了健康、教育和人道主義救援等領(lǐng)域的公益項目。默克雪蘭諾：在健康領(lǐng)域，自2009年起，默克開展了中國甲狀腺疾病健康教育項目，在國際甲狀腺周期間向公眾提供免費檢測和義診活動。同時，默克與北京市紅十字基金會合作共同啟動愛必妥?慈善援助項目 [15]，旨在幫助已確認在愛必妥?治療中明顯獲益的經(jīng)濟困難的晚期結(jié)直腸癌患者，使其獲得生命延長，并幫助部分患者獲得治愈的機會。在教育領(lǐng)域，默克雪蘭諾于2010年宣布投入600萬元人民幣，在全國12個城市的20所醫(yī)藥院校，設(shè)立資助貧困醫(yī)科低年級大學(xué)生的“默克雪蘭諾企業(yè)社會責任基金勵學(xué)金”和獎勵優(yōu)秀高年級學(xué)生的“默克雪蘭諾中國精英獎學(xué)金”。在人道主義救援領(lǐng)域，默克雪蘭諾和員工在2008年為四川汶川地震共同捐贈1百多萬元人民幣；2010年，“默克雪蘭諾企業(yè)社會責任基金”援助西南旱災(zāi)和玉樹地震災(zāi)區(qū)，捐出善款20萬元人民幣。默克化工：2007年5月，默克化工中國向中國國家納米科學(xué)中心捐贈科研用實驗室試劑，旨在進一步促進和推動雙方科研的長期合作，為中國科研事業(yè)的長足發(fā)展吸引更多的力量。2008年5月，默克化工中國攜手其它國際化工公司，在北京共同簽署了由國際化學(xué)品制造商協(xié)會贊助的“責任關(guān)懷北京宣言”，致力于“責任關(guān)懷”項目在中國的支持和實踐。通過這項國際志愿發(fā)起活動，化工行業(yè)相互協(xié)作持續(xù)努力提高國內(nèi)健康、安全和環(huán)境方面的表現(xiàn)。2012年，默克中國在上海5所小學(xué)開展了“默克中國校園凈水項目 [16]”，是默克中國開展的第一個本地社會責任項目，通過捐贈硬件設(shè)施、開展志愿者環(huán)保課堂，旨在改善學(xué)校水質(zhì)量，尤其是外來務(wù)工人員子女就讀學(xué)校的水質(zhì)量，并提高學(xué)生環(huán)保意識。2014年，默克化工中國成為創(chuàng)行中國的戰(zhàn)略合作伙伴，默克通過創(chuàng)行這個平臺，推動本地社會責任項目發(fā)展，支持創(chuàng)行學(xué)生團隊的公益項目。 [17]默克化工中國連續(xù)三年參加在上海張江高科技園區(qū)舉行的“張江樂跑 [18]”活動，并向賽事合作方上海國際社區(qū)中心旗下的兩個主題慈善活動Giving Tree 和River of the Heart捐款，為推進中國環(huán)境保護做貢獻。默克“綠晶”項目是由默克電子科技業(yè)務(wù)中國區(qū)于2017年發(fā)起的企業(yè)社會責任項目，在宣傳智能設(shè)備環(huán)保使用的同時，關(guān)注中國西部偏遠地區(qū)的基礎(chǔ)教育。 [54]2018年，默克攜手壹基金，全方位支持農(nóng)村學(xué)校飲用水改善項目“凈水計劃”。從2018年起，默克中國的每名員工都將響應(yīng)壹基金人人公益的號召，每天捐出一元錢人民幣投入“凈水計劃”。同時，默克中國還將為“凈水計劃”提供水質(zhì)檢測設(shè)備及技術(shù)支持，和壹基金一起在農(nóng)村地區(qū)水質(zhì)快速分析與檢測方面合作。此外，默克也將借助壹基金這個項目的廣大平臺，為農(nóng)村地區(qū)疾病教育做出貢獻。 [55]新手上路成長任務(wù)編輯入門編輯規(guī)則本人編輯我有疑問內(nèi)容質(zhì)疑在線客服官方貼吧意見反饋投訴建議舉報不良信息未通過詞條申訴投訴侵權(quán)信息封禁查詢與解封?2024?Baidu?使用百度前必讀?|?百科協(xié)議?|?隱私政策?|?百度百科合作平臺?|?京ICP證030173號?京公網(wǎng)安備110000020000

MECK_百度百科

_百度百科網(wǎng)頁新聞貼吧知道網(wǎng)盤圖片視頻地圖文庫資訊采購百科百度首頁登錄注冊進入詞條全站搜索幫助首頁秒懂百科特色百科知識專題加入百科百科團隊權(quán)威合作下載百科APP個人中心收藏查看我的收藏0有用+10MECK播報討論上傳視頻品牌本詞條缺少概述圖，補充相關(guān)內(nèi)容使詞條更完整，還能快速升級，趕緊來編輯吧！MECK，是長沙市滑板之家體育用品有限公司旗下品牌， [1]MECK品牌誕生于德國拜仁，由Julienne Meck在自家車庫創(chuàng)建并手工制作第一塊MECK滑雪單板， [2]是一個專做單板滑雪的運動品牌，主營業(yè)務(wù)是滑雪單板，陸地沖浪板，滑雪服等運動器材。 [2]外文名MECK所屬公司長沙市滑板之家體育用品有限公司商標注冊號44770608 [1]國際分類28 [1]目錄1品牌發(fā)展2產(chǎn)品及服務(wù)3品牌價值觀4品牌故事5制作工藝品牌發(fā)展播報編輯1998年3月，建立工廠，同年9月發(fā)布第一款MECK單板滑雪單板板；2000年9月，品牌發(fā)布MECK滑雪板產(chǎn)品第二代；2005年1月，MECK建立獨立生產(chǎn)線； [2]2018年3月，推出全新工藝聚氨酯防撞邊墻，比傳統(tǒng)abs邊墻耐撞度高8倍； [2]2020年1月，進入中國市場； [2]2021年3月，推出陸地沖浪板支線。2021年9月，推出全新產(chǎn)品兩用型單板快穿固定器以及快穿雪鞋。 [2]產(chǎn)品及服務(wù)播報編輯單板滑雪類：MECK滑雪單板，單板快穿固定器，滑雪鞋，滑雪板包，滑雪裝備包?；孱悾簃eck陸地沖浪板 [2]品牌價值觀播報編輯創(chuàng)新、實踐、挑戰(zhàn)、分享 [2]品牌故事播報編輯MECK從公司成立第一天起，就全心投入產(chǎn)品的開發(fā)與研究。隨著時間的過程不斷發(fā)展和創(chuàng)新，生產(chǎn)了許多富有科技及個性的單板產(chǎn)品，現(xiàn)在MECK品牌不僅擁有獨立的生產(chǎn)線以及生產(chǎn)技術(shù)，再研發(fā)和制造過程中，不斷完善產(chǎn)品、創(chuàng)新以確保滿足客戶需求。2020年初進入中國市場，MECK一直為推動滑雪運動和支持單板滑手做出極大的貢獻。品牌一直專注于創(chuàng)新設(shè)計和提高產(chǎn)品的性價比，讓更多人能夠接觸并愛上單板滑雪這項運動。 [2]制作工藝播報編輯單板采用聚氨酯防撞邊墻工藝，是一種有彈性的pu材質(zhì)，耐撞性是普通abs邊墻的8倍，pu邊墻的唯一缺點是不夠光滑，所以邊墻看上去比較樸實無華。 [2]新手上路成長任務(wù)編輯入門編輯規(guī)則本人編輯我有疑問內(nèi)容質(zhì)疑在線客服官方貼吧意見反饋投訴建議舉報不良信息未通過詞條申訴投訴侵權(quán)信息封禁查詢與解封?2024?Baidu?使用百度前必讀?|?百科協(xié)議?|?隱私政策?|?百度百科合作平臺?|?京ICP證030173號?京公網(wǎng)安備110000020000

Meck是什么意思_Meck的翻譯_音標_讀音_用法_例句_愛詞霸在線詞典

是什么意思_Meck的翻譯_音標_讀音_用法_例句_愛詞霸在線詞典首頁翻譯背單詞寫作校對詞霸下載用戶反饋專欄平臺登錄Meck是什么意思_Meck用英語怎么說_Meck的翻譯_Meck翻譯成_Meck的中文意思_Meck怎么讀,Meck的讀音,Meck的用法,Meck的例句翻譯人工翻譯試試人工翻譯翻譯全文Meck釋義[人名] 梅克點擊人工翻譯，了解更多人工釋義實用場景例句全部A letter from Nadyezhda von Meck written in a tone she had never before used.娜蒂契達·馮·梅克用她從未用過的語氣給他寫了一封信.互聯(lián)網(wǎng)收起實用場景例句釋義實用場

MEK inhibition reprograms CD8+ T lymphocytes into memory stem cells with potent antitumor effects | Nature Immunology

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Published: 23 November 2020

MEK inhibition reprograms CD8+ T lymphocytes into memory stem cells with potent antitumor effects

Vivek Verma?

ORCID: orcid.org/0000-0001-8129-41401,2, Nazli Jafarzadeh1, Shannon Boi?

ORCID: orcid.org/0000-0001-9479-56653, Subhadip Kundu1, Zhinuo Jiang?

ORCID: orcid.org/0000-0003-2059-20771, Yiping Fan4, Jose Lopez1, Rahul Nandre1?nAff7, Peng Zeng2?nAff8, Fatmah Alolaqi1, Shamim Ahmad2?nAff9, Pankaj Gaur1, Simon T. Barry5, Viia E. Valge-Archer5, Paul D. Smith5, Jacques Banchereau?

ORCID: orcid.org/0000-0003-3535-72216, Mikayel Mkrtichyan1, Benjamin Youngblood?

ORCID: orcid.org/0000-0002-1261-99573, Paulo C. Rodriguez?

ORCID: orcid.org/0000-0001-7480-65662?nAff10, Seema Gupta?

ORCID: orcid.org/0000-0003-0106-595X1,2 & …Samir N. Khleif?

ORCID: orcid.org/0000-0003-2707-52241,2?Show authors

Nature Immunology

volume?22,?pages 53–66 (2021)Cite this article

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CancerImmunology

AbstractRegenerative stem cell–like memory (TSCM) CD8+ T cells persist longer and produce stronger effector functions. We found that MEK1/2 inhibition (MEKi) induces TSCM that have naive phenotype with self-renewability, enhanced multipotency and proliferative capacity. This is achieved by delaying cell division and enhancing mitochondrial biogenesis and fatty acid oxidation, without affecting T cell receptor-mediated activation. DNA methylation profiling revealed that MEKi-induced TSCM cells exhibited plasticity and loci-specific profiles similar to bona fide TSCM isolated from healthy donors, with intermediate characteristics compared to naive and central memory T cells. Ex vivo, antigenic rechallenge of MEKi-treated CD8+ T cells showed stronger recall responses. This strategy generated T cells with higher efficacy for adoptive cell therapy. Moreover, MEKi treatment of tumor-bearing mice also showed strong immune-mediated antitumor effects. In conclusion, we show that MEKi leads to CD8+ T cell reprogramming into TSCM that acts as a reservoir for effector T cells with potent therapeutic characteristics.

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Fig. 1: MEKi supports the expansion of activated effector T cells in the TME leading to reduced tumor growth.Fig. 2: MEKi-treated CD8+ T cells have enhanced mitochondrial respiration fueled by FAO.Fig. 3: Metabolomic and lipidomic analysis of MEKi-treated CD8+ T cells.Fig. 4: MEKi induces stem cell memory characteristics in CD8+ T cells.Fig. 5: MEKi induces stem cell memory in human CD8+ T cells that is intermediate between that of Tnaive and TCM cells.Fig. 6: MEKi induces TSCM cells by delaying cell division, proliferation and differentiation.Fig. 7: MEKi induces FAO-mediated stem cell memory in T cells.Fig. 8: MEKi-treated CD8+ T cells have higher recall responses leading to stronger TSCM-mediated antitumor effects after ACT.

Data availability

For healthy adult donors, PBMCs were collected through the St. Jude’s Blood Bank; samples for WGBS were collected under institutional review board protocol no. XPD15-086 as published earlier32. In vitro, in vivo and flow cytometry data are included in this published article and its Extended Data Figures. All other relevant data are available from the corresponding author upon reasonable request. Source data are provided with this paper.

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Download referencesAcknowledgementsWe are grateful to Jeannie and Tony Loop for their generous support to SNK’s laboratory. We acknowledge the Georgia Cancer Center, Augusta University internal support grant to S.N.K. and Flow Cytometry Core Facility at Lombardi Comprehensive Cancer Center. We acknowledge the Metabolomics and Flow Cytometry/Cell Sorting Shared Resource in Georgetown University, which is partially supported by NIH/NCI/CCSG grant P30-CA051008 and NIH S10 grant S10OD016213. We thank S. Bansal for technical assistance with LC–MS data acquisition and S. Li for LC–MS data processing and analysis. This study was supported in part by NIH grant 1 R01 CA237311 01A1 to B.Y. and NIH grants R01-CA184185, R01-CA233512 and P30-CA076292 and The Florida Department of Health grant no. 20B04 to P.C.R. We acknowledge the contribution of P. Finger from the electron microscopy service at the Jackson Laboratory for assistance with electron microscopy.Author informationAuthor notesRahul NandrePresent address: Division of Preclinical Innovation, National Center for Advancing Translational Sciences, NIH, Rockville, MD, USAPeng ZengPresent address: Department of Pharmacology, Case Western Reserve University, Cleveland, OH, USAShamim AhmadPresent address: Kite Pharma/A GILEAD Company, Emeryville, CA, USAPaulo C. RodriguezPresent address: H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USAAuthors and AffiliationsThe Loop Immuno-Oncology Laboratory, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USAVivek Verma,?Nazli Jafarzadeh,?Subhadip Kundu,?Zhinuo Jiang,?Jose Lopez,?Rahul Nandre,?Fatmah Alolaqi,?Pankaj Gaur,?Mikayel Mkrtichyan,?Seema Gupta?&?Samir N. KhleifGeorgia Cancer Center, Augusta University, Augusta, GA, USAVivek Verma,?Peng Zeng,?Shamim Ahmad,?Paulo C. Rodriguez,?Seema Gupta?&?Samir N. KhleifDepartment of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, USAShannon Boi?&?Benjamin YoungbloodCenter for Applied Bioinformatics, St. Jude Children’s Research Hospital, Memphis, TN, USAYiping FanBioscience, Early Oncology, AstraZeneca, Cambridge, UKSimon T. Barry,?Viia E. Valge-Archer?&?Paul D. SmithThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USAJacques BanchereauAuthorsVivek VermaView author publicationsYou can also search for this author in

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PubMed?Google ScholarContributionsV.V., S.G. and S.N.K. conceived the study and designed the experiments. V.V. performed the experiments with input from N.J., S.K., Z.J., J.L., R.N., P.Z., F.A., S.A., P.G. and M.M. S.T.B., V.E.V.-A. and P.D.S. supplied the materials. B.Y. and S.B. performed the methylation experiment. Y.F. analyzed the whole-genome bisulfite sequencing. J.B. helped with the electron microscopy and, along with B.Y. and S.B., was involved in numerous discussions and reviewed the manuscript. P.C.R. helped with the metabolic assays. V.V., S.G. and S.N.K. analyzed the data and wrote the manuscript. S.N.K. supervised the study.Corresponding authorCorrespondence to

Samir N. Khleif.Ethics declarations

Competing interests

S.N.K. and V.V. are inventors on patent applications related to work on the induction of TSCM by MEK1/2 inhibition in T cells and methods for use of these TSCM in various therapeutic applications. S.N.K. reports honoraria from Syndax, IOBiotech, Bioline Therapeutics, Northwest Biotherapeutics, Advaxis, EMD Serono, GSK, UbiVac, McKinsey, AstraZeneca and Lycera. S.N.K. reports stocks or ownership interest in Advaxis, GeorgiaImmune, IOBiotech and Northwest Therapeutics. S.N.K. is a consultant for Syndax, IOBiotech, Bioline, Kahr, PDS Biotechnology, AstraZeneca, CytomX, NewLink Genetics, AratingaBio, CanImGuide and Lycera. S.N.K. is a board member for Advaxis. S.N.K. has research contracts with Syndax, IOBiotech, Bioline Therapeutics, AstraZeneca, MedImmune and Lycera. J.B. is on the Board of Directors of Neovacs and Stamford Pharmaceutical and is a member of the CUE Biopharma and GeorgiaImmune SABs. J.B. reports stock or ownership interest in Neovacs, Stamford Pharmaceuticals and Cue Biopharma. J.B. has a research contract with Sanofi.

Additional informationPeer review information Zoltan Fehervari was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Extended dataExtended Data Fig. 1 MEKi enhances mitochondrial respiration in CD8+ T cells.Related to Figs. 1 and 2. a, Frequencies of phosphorylated-(p)-MEK1/2 and ERK1/2 CD8+ T cells in the TME as estimated by FACS analysis. Representative data from one of two experiments are shown. Each symbol corresponds to one mouse with the indicated number of mice per group given in parentheses. The error bars indicate the s.e.m. Statistical analysis was performed by unpaired, one-tailed Student’s t-test (*P≤0.05). b, Determination of effect of inhibition of mitochondrial respiration by oligomycin on proliferation (by VCT dilution) of gp100-activated and MEKi-treated CD8+ T cells. Representative results from one of two experiments performed in triplicates are shown. The error bars indicate the s.e.m. Statistical analysis was performed by unpaired, one-tailed Student’s t-test (*P≤0.05; **P≤0.01; ****P≤0.0001).Extended Data Fig. 2 Expression profiles for markers of proliferation, memory, activation, apoptosis, effector functions and exhaustion on in vitro MEKi-treated pMel-1 CD8+ T cells and effects of MEKi, trametinib on TSCM induction and cellular metabolism.Related to Figs. 4 and 6. a–d, Scheme of pMel-1 CD8+ T cell activation and analysis (a); FACS analysis of Ki67+ (b); CD95+ and CCR7+ (c); CXCR5+ and IL2Rβ+ (d) in CD62L+CD44– CD8+ T cells after various treatments as shown in figures. Representative results from one of two experiments performed in triplicates are shown. The error bars indicate the s.e.m. Statistical analysis was performed by unpaired, one-tailed Student’s t-test (*P≤0.05; **P≤0.01; ***P≤0.001; ****P≤0.0001; ns: non-significant). e–g, FACS micrographs showing the cell phenotype in the naive compartment (CD62L+CD44–) after 48 h activation under various conditions as shown in picture (e); FACS analysis of expression of IFN-γ, Granzyme B, Perforin, KLRG1 and Eomes on CD62L+CD44– cells in the naive cell compartment (marked by dotted red arrows) (f); Expression levels of mRNA of various effector and exhaustion markers relative to Actb after in vitro activation of pMel-1 CD8+ T cells with gp100 with/without MEKi (g). Experiments were repeated twice with similar results and representative results from one experiment are shown. The error bars indicate the s.e.m. Statistical analysis was performed by unpaired, one-tailed Student’s t-test (**P≤0.01; ***P≤0.001; ****P≤0.0001). h–j, Comparative analysis of induction of TSCM cells (h); Estimation of FA (i) and glucose (j) uptake in CD8+ T cells that were activated in the presence of selumetinib or trametinib. Representative results from one of two experiments performed in triplicates are shown. The error bars indicate the s.e.m. Statistical analysis was performed by unpaired, one-tailed Student’s t-test (****P≤0.0001).Extended Data Fig. 3 In vitro analysis of effect of MEK1 and MEK2 knock down (MEK1/2KD) using siRNA on generation of naive and TSCM cells.Related to Fig. 4. a, b, Confirmation of knock down of MEK1 (a) and MEK2 (b) by FACS analysis after siRNA treatment. Data are representative of two experiments performed in triplicates. The error bars indicate the s.e.m. Statistical analysis was performed by unpaired, one-tailed Student’s t-test (***P≤0.001; ****P≤0.0001). c, d, Relative frequencies of CD62L+CD44– cells (c) and mitochondrial potential (TMRM) (d) of CD8+ T cells in which MEK1/2 was knocked down. Data are representative of three experiments performed in triplicate. The error bars indicate the s.e.m. Statistical analysis was performed by unpaired, one-tailed Student’s t-test (**P≤0.01; ****P≤0.0001) e, Memory phenotypes generated after MEK1KD or MEK2KD in pMel-1 CD8+ T cells. Data are representative of two experiments performed in triplicates.Extended Data Fig. 4 Gating strategy and methylation status of MEKi-treated CD8+ T cells.Related to Figs. 5 and 7. a, Gating strategy for generation of TSCM cells from human CD8+ T cells. b, A graphical representation of the number of DMRs among the MEKi TSCM (one WGBS sample) versus freshly isolated naive, bonafide TSCM, TCM, and TEM (one WGBS sample for each) from healthy donors (HD). c, Statistical analysis of the methylation status of human TNAIVE, TSCM and TCM cells at Ifng, Prf1 and Tcf7 gene loci, as noted in the figure (related to Fig. 5e–g). Representative data from one of two experiments is shown. The error bars indicate the s.e.m. Statistical analysis was performed by unpaired, one-tailed Student’s t-test (*P≤0.05; **P≤0.01; ****P≤0.0001). d, Estimation of CD62L and CD44 on pMel-1 CD8 cells after activation under various conditions as listed in the figure. Representative results from one of three experiments performed in triplicates are shown. The error bars indicate the s.e.m. Statistical analysis was performed by unpaired, one-tailed Student’s t-test (****P≤0.0001; ns: non-significant).Extended Data Fig. 5 Frequency of CD8+ T cells in various tissues following ACT, the expression levels of mTORC1 in MEKi-treated CD8+ T cells, and a proposed model for MEKi-mediated TSCM generation.Related to Fig. 8. a, The frequency of CD8+ T cell engrafted in spleen and tumors of mice that received variously treated pMel-1 CD8+ T cells (48 h post-T cell infusion). FACS analysis of the tumor and spleen samples was performed by gating upon Thy1.1 cell population. A representative of two experiments is shown. Each symbol corresponds to one mouse with the indicated number of mice per group given in parentheses. The error bars indicate the s.e.m. Statistical analysis was performed by unpaired, one-tailed Student’s t-test. Significant differences in engraftment were not observed between MEKi-treated and untreated spleen and tumor samples. b, Loci-specific bisulfite sequencing analysis of the Ifng and Prf1 in TCM CD8+ T cells generated after activation of human CD8+ T cells with anti-CD3/28 with or without MEKi treatment. Horizontal lines represent individual sequenced clones from the pool of FACS-purified CD8+ T cells. Bar graphs represent the frequencies of methylated CpGs in respective sample as shown in the figure. Representative data from one of two experiments are shown. c, Estimation of numbers of adoptively transferred cells in tumors of variously treated mice. The mice were sacrificed at 22 days after ACT and tumors were harvested. Samples were stained and processed for FACS analysis. A representative of two experiments is shown. Each symbol represents one mouse with the indicated number of mice per group given in parentheses. The error bars indicate the s.e.m. Statistical analysis was performed by unpaired, one-tailed Student’s t-test (*P≤0.05). d, Levels of phosphorylated-(p)-mTORC1 and total mTORC1 in MEKi-treated mouse CD8+ T cells during initial cell activation and following antigenic re-challenge as detailed in the figure. Expression of β-actin is shown as a control. Number on the bands show band intensity. Experiments were repeated twice with similar results. e, Proposed model for MEKi-mediated TSCM generation. Inhibition of MEK1/2 during antigen-activation of naive cells: 1) results in a decrease in the levels of ERK1/2 and cyclin D1, delaying cell division and accumulating these cells in early phases of differentiation; 2) results in an increase in PGC1α and its downstream SIRT3, enhancing FAO-mediated metabolic fitness that drives memory generation; and 3) does not affect PI3K-Akt-mediated T cell activation. This crosstalk between MAPK pathway, cellular metabolism and TCR-mediated signaling after MEK-inhibition leads to induction of memory characteristics in naive CD8+ T cells, generating TSCM. These TSCM produce highly activated effector cells following re-stimulation with the cognate antigen resulting in robust recall responses.Source dataSupplementary informationReporting SummarySource dataSource Data Fig. 5A list of the top 3,000 CpG sites across samples.Source Data Extended Data Fig. 5Unprocessed blots.Rights and permissionsReprints and permissionsAbout this articleCite this articleVerma, V., Jafarzadeh, N., Boi, S. et al. MEK inhibition reprograms CD8+ T lymphocytes into memory stem cells with potent antitumor effects.

Nat Immunol 22, 53–66 (2021). https://doi.org/10.1038/s41590-020-00818-9Download citationReceived: 11 March 2020Accepted: 08 October 2020Published: 23 November 2020Issue Date: January 2021DOI: https://doi.org/10.1038/s41590-020-00818-9Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard

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