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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 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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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全球知名药企：默沙东和默克，你还傻傻分不清吗？ - 知乎

全球知名药企：默沙东和默克，你还傻傻分不清吗？ - 知乎首发于疫苗公司切换模式写文章登录/注册全球知名药企：默沙东和默克，你还傻傻分不清吗？e苗君预约HPV疫苗关注济苗通你有没有发现：默克和默沙东两家公司的百科上，英文名字都是Merck，但是中文却大不相同。这是为什么？其实这里面有一个令人感慨的“血缘”故事，今天苗苗酱就来跟大家分享一下。1668年，一个叫默克（弗雷德里奇·杰考伯·默克）的人收购了位于德国达姆施塔特的天使药房，开启了他的创业之路。发展到1816年，默克的后代——海因里希·伊曼纽尔·默克接管了天使药房，但是拥有雄心壮志的他不满足于现状，于是开始着手将天使药房发展成一个全球化的公司。由于默克公司的全球业务开展的非常成功，所以在1891年，默克在美国纽约成立了分公司——Merck& Co.。后来，第一次世界大战发生了，默克公司作为一个跨国企业，不可避免地受到了战争的影响，进而丧失了很多海外子公司，其中包括Merck& Co.。1917年，默克位于美国的子公司Merck& Co.因为战争被没收，所以从此默克与Merck& Co.被迫分家了。1953年，默克与费城的Sharp&Dohme公司合并，这也是默沙东名字的由来。自此以后，默克集团作为默克品牌的创立者，拥有默克（Merck）名称和商标在除北美以外的全球范围内的使用权，在北美地区，默克使用“EMD”名称。Merck & Co.仅在北美地区拥有“默克”名称的使用权，在北美以外地区必须使用“MSD”或“MSD Sharp & Dohme”、“Merck Sharp & Dohme”。默克和默沙东虽然是一脉相传，都是做医药行业起家，但是现在两家公司的主营业务却不太一样。默沙东公司主要致力于处方药、动物保健、治疗及控制，以及疫苗等广泛的医疗领域，以实现拯救生命、提高全人类健康水平的目标，还将研发领域扩展到诸如生物制剂等新的领域。默克公司主要致力于创新型制药、生命科学以及前沿功能材料技术，并以技术为驱动力，为患者和客户创造价值。综上来说，我们打的疫苗、用的处方药，只要上面标注的是MSD，就是默沙东，如果是Merck，则是默克公司。看到这，你是不是能分清谁是谁了呢？关于默沙东的故事，苗苗酱就介绍到这里啦。你还想知道哪个医药公司的故事？可以在后台告诉苗苗酱哦~发布于 2021-01-29 10:45制药企业制药跨国公司赞同 438 条评论分享喜欢收藏申请转载文章被以下专栏收录疫苗公司全球知名疫苗公

默克_百度百科

度百科网页新闻贴吧知道网盘图片视频地图文库资讯采购百科百度首页登录注册进入词条全站搜索帮助首页秒懂百科特色百科知识专题加入百科百科团队权威合作下载百科APP个人中心收藏查看我的收藏0有用+10默克播报讨论上传视频药物贸易企业默克是一家科技公司，专注于医药健康、生命科学和电子科技三大领域， [56]全球超过60,000名员工服务于默克。从基因编辑技术和发现治疗具有挑战性疾病的独特方法，到实现设备的智能化——默克无处不在。2021年，默克在66个国家的总销售额达197亿欧元， [57]集团销售额增长12.3%。 [58]默克家族作为公司的创始者持有默克大部分的股份，除美国和加拿大例外，在全球都叫“默克”，默克的三大领域：医药健康、生命科学及电子科技在这两个国家分别称之为“EMD Serono”、“MilliporeSigma”和“EMD Electronics”。 [62]默克在中国已经有89年发展历史， [59]第一个分公司最早于1933年在上海成立 [60]。默克在中国有超过4,500名员工，在北京、上海、香港、无锡、苏州和南通有21个注册公司。 [61]中国是默克在全球最为重要的战略国家之一，并且已成为默克的一个全球创新中心 [63]。近些年来，默克在南通的医药健康和生命科学业务以及在上海的电子科技业务分别进行有1.7亿欧元、8000万欧元和4400万欧元的投资。此外，默克还在北京设立了全球生物制药研发中心，在上海设有显示材料研发中心和生命科学实验室 [64]，在苏州设有光刻材料研发中心 [65]。默克在上海和广东分别设立了两家中国创新中心 [66]和一个创新基地 [67]。公司名称默克外文名Merck KGaA成立时间1668年总部地点德国达姆施塔特市经营范围创新型制药、生命科学和电子科技等 [21]公司类型独资公司口号创新引领生活 Living Innovation年营业额177亿美元（2018年） [3]员工数6 万人 [20]董事会主席Karl-Ludwig Kley目录1品牌历史2荣誉3默克之道4公司业务5默克在中国6企业责任▪全球项目▪中国项目品牌历史播报编辑起源于天使药房的传奇1668 年，弗雷德里奇·杰考伯·默克（Friedrich Jacob Merck，1621-1678）收购位于达姆施塔特的天使药房（Engel-Apotheke，英语: Angel Pharmacy），开启企业发展之路，天使药房也成为之后家族公司的起源。1816年，海因里希·伊曼纽尔·默克（Heinrich Emanuel Merck，1794-1855）接管天使药房，开始将其发展成为一个全球化公司。他首度开始工业化规模生产。在医药界，他为简单手工技艺向科技生产的转变奠定了基础。1827 年，海因里希·伊曼纽尔·默克开始了工业化的大规模生产1900年，默克在全球所有大陆地区拥有分支机构或代表1904年，首次列入医学用药产品；开始了液晶材料的研究1917年，在美国的子公司被没收，默克与默沙东两个公司从此独立1945年，默克损失部分海外分支机构, 在废墟中开始重建1971年，继亚洲、拉丁美洲后，在美国重新设立子公司“EMD”1995年，建立德国默克集团（Merck KGaA），并正式在法兰克福证交所上市。24亿德国马克的发行量在当时的德国创立了最大公开发行股票量的历史纪录2003年，Erbitux®进入靶向癌症治疗领域2007年，默克收购瑞士雪兰诺，进军顶尖生物科技领域2010年，默克收购美国密理博，奠定其在全球生命科学市场的引先地位2012年，默克在全球广泛开启“Fit For 2018”转型项目2014年，默克收购安智电子材料，同年，发起对西格玛奥德里奇公司的收购2024年，默克宣布将收购Harpoon Therapeutics [74]“默克”品牌的创始者由于在美国出口业务的成功开展，默克公司在纽约成立了一个分公司。1891年，默克美国分公司Merck& Co. 正式成立。第一次世界大战期间默克丧失了很多海外子公司，其中包括Merck & Co.。1917年，Merck& Co.已成为一家独立的公司。如今这两家公司虽同名，但并无其它关联。默克集团作为默克品牌的创立者，拥有“默克（Merck）”名称和商标在全球范围（除北美地区外）的使用权。在北美地区，默克使用“EMD”名称，源自达姆施塔特的伊曼纽尔·默克（Emanuel Merck Darmstadt）的首字母缩写。Merck & Co.仅在北美地区拥有“默克”名称的使用权，在北美以外地区必须使用“MSD”或“MSD Sharp & Dohme”、“Merck Sharp & Dohme”。默克集团管理团队默克集团管理团队 [68]Allan GaborAllan Gabor安高博默克中国总裁兼电子科技业务中国区董事总经理 [69]荣誉播报编辑默克集团被IMD Lombard Odier2009全球家族企业奖评为“最佳家族企业”默克跨部门的创新项目Innospire荣获“生物信息技术知识管理最佳实践奖”波士顿商业杂志授予默克密理博业务分支“BBJ环保奖”，嘉奖其回收及循环再造计划SID Display Week认可默克公司和LG Chem公司联合开发的应用于高性能3D显示器的FPR技术R&D杂志授予默克密理博业务分支“R&D100奖项”，嘉奖其Samplicity®过滤系统为2012年度最具影响意义的100项产品 [1]默克达姆施塔特的创新包装理念荣获2012年德国物流协会“德国物流奖”默克家族和默克集团以其公司的文化和社会责任荣获2012年马丁·路德国际基金会“路德玫瑰”奖项默克雪兰诺在《科学》杂志最佳雇主的评选中连续三年位于生命科学公司前10位 [2]2020年5月13日，默克名列2020福布斯全球企业2000强榜第308位。 [3-4]2021年5月，默克位列“2021福布斯全球企业2000强”第232位。 [19]2022年12月9日，默克集团以17,550亿人民币位列《2022胡润世界500强》第29名。 [71]2023年6月，入选福布斯发布的2023年福布斯全球企业2000强榜单，位列第73名。 [72]默克之道播报编辑默克文化是默克行为的基石。默克文化：“忠于自我。默克集团始终信奉企业的成功构筑在以人为本的基础上。该集团的企业文化让每个人都彰显其不同之处。这种文化以相互尊重和强烈的认同感为基础。”默克之道意味着承担责任，设定质量标准，继续积极地以创新的理念改变未来。价值观默克的六大价值观界定了默克的工作方式。默克企业价值观包括责任、尊重、诚信、透明、勇气和成就。勇气：开启未来之门。成就：使我们的企业成功成为可能。责任：决定了我们的企业作为。尊重：是一切合作的基础。诚信：是我们的信用保证。透明：使相互信赖成为可能。默克logo公司口号及使命宣言2013年，默克以“创新引领生活 Living Innovation”作为新的标语，意味着该集团会释放科研的潜力，为客户提供高质量产品；并致力于改善患者和客户的生活，努力优化组织构架和流程，提升公司竞争力。全新的口号意味着该集团将“创新”视为企业不可分割的一部分，以“创新”决定他们是谁、做什么。 [5]工作在默克默克在全球范围内提供卓越的工作以及国际化的职业发展机会，并持续招募优秀的毕业生和经验丰富的职业人加入团队。该集团除了招聘、吸引尖端人才外，还为员工提供培训机会。默克在参与总部发起的全球培训项目的同时，也专门为本地员工建立了学习中心，为其员工创造发挥才能的契机。公司业务播报编辑默克旗下三大业务领域 [6]医药健康生命科学高性能材料医药健康生命科学高性能材料治疗，例如，癌症，多发性硬化症以及不孕不育等疾病的处方药；日常保健或缓解感冒和疼痛症状的非处方药；以及在过敏症和生物仿制药领域的创新。为生命科学行业提供创新性工具和实验室用品，使研究和生物技术生产更容易、更快速、更成功。包罗万有的特殊化学制品，如液晶显示屏、用于涂料和化妆品的效果颜料，或是电子行业的高新技术材料。该业务领域旗下业务默克雪兰诺消费者健康生物仿制药阿罗格默克密理博高性能材料默克雪兰诺业务默克雪兰诺是默克集团旗下的生物制药业务分支。在美国和加拿大以EMD 雪兰诺的名称运营。默克雪兰诺长期致力于发展专科治疗领域业务，包括生殖领域、肿瘤领域、心血管领域、外科及急重症领域、甲状腺领域、糖尿病领域、其它内分泌领域和变态反应性领域。默克雪兰诺在全球拥有超过16,000名员工，致力于发现、开发、制造和销售处方药品，这些药品远销150多个国家。 [7]该公司结合生物技术和医药化学方面的专长以及对专注的治疗领域的深刻了解，采用灵活的方法寻找最适合的疾病治疗药物。默克雪兰诺公司开发和生产上述两种来源的新分子实体都取得成功，这让公司在药物开发过程中的各个阶段，都能充分发掘生物和化学领域的药物开发的最大潜力。主要产品 [1]肿瘤:肿瘤靶向治疗:爱必妥®(转移性结直肠癌, 头颈癌)神经变性疾病利比®, Novantrone® (多发性硬化)生殖:在生殖周期每一阶段帮助不孕夫妇: 果纳芬®,艾泽®, 乐芮®, 思则凯®, 雪诺酮®, Pergoveris™内分泌:与HIV相关的消瘦 (Serostim®)与HIV相关的脂肪代谢障碍 (Egrifta™)苯丙酮尿症(科望®)心脏代谢治疗:2型糖尿病 (Glucophage® 家族)心血管疾病 (康忻® β -阻滞剂家族)甲状腺疾病 (优甲乐®)消费者健康业务消费者健康业务分支在全球拥有超过2000名员工，推动研究和创新，以帮助世界各地的消费者过上更好的生活。旗下品牌行销全球100多个国家。除欧洲市场外，消费者健康业务分支在南美和亚洲的新兴市场迅速发展。 [1]主要产品 [1]自我治疗药品骨关节: 改善骨关节灵活性的产品，如Flexagil®, Seven Seas ®, SevenSeas® JointCare, Kytta®日常保健: 维生素和矿物质,如Bion®3, Multibionta®, Cebion®, Diabion®,妇女和儿童保健:Femibion®, Kidabion® (Haliborange®)咳嗽和感冒: Nasivin®, Sedalmerck®高性能材料业务液晶材料液晶材料是高性能材料部门的关键产品，主要应用于电视机，笔记本电脑，数码相机，手提电话的液晶显示器和其它高品质显示器。该部门视新的照明和显示技术为重点技资领域。效果颜料与化妆品材料默克是珠光颜料的主要供应商之一，该公司的珠光颜料先后获得了400多项专利。该公司的珠光颜料广泛应用于汽车工业，塑料工业，印刷工业以及化妆品工业等领域。该集团还提供功能性的颜料。 [1]主要产品 [1]显示材料事业部:· 液晶显示材料· 光刻胶颜料和功能性材料事业部:· 涂料用珠光颜料· 印刷和塑料工业用珠光颜料· 应用于防伪技术的效果颜料· 食品和药品用颜料· 功能性材料· 化妆品活性成分和珠光颜料先进技术事业部:· 有机发光二极管（OLED）· 光电伏材料· 照明用材料集成电路材料事业部:· 用于集成电路生产的电介质、二氧化硅、平版印刷、增产剂、边缘光刻胶去除剂以及其他配套产品默克密理博业务默克集团旗下的默克密理博业务，为全球生命科学用户提供完整的产品线和强大的创新能力。默克密理博拥有4万多种产品，是生命科学行业三大供应商之一。该部门由三个事业部组成：生命科学部、实验室解决方案部和过程工艺解决方案部。 [1]主要产品 [1]生物科学:提供制药和生物科学领域研究所需的产品提供蛋白质和细胞生物学研究所需括仪器，耗材和试剂等产品和服务实验室解决方案:研发、科研及工业实验室所需的化学品及相关材料制药、食品和诊断行业取样及检测平台所需的产品和服务科研和工业实验室超纯水制备所需的产品、耗材和服务过程工艺解决方案:为制药和生物制药生产企业提供相关产品与服务默克在中国播报编辑1897年，默克开展了中国的业务，通过上海、广州、天津等口岸向中国销售高纯度的化学试剂。默克公司在中国主要发达城市北京、上海、广州、香港都有分公司或代表处。随着经济持续增长，中国已经成为世界关注的焦点和最受欢迎的外资投放市场。对于默克，这也意味着绝佳机遇。默克公司依靠其优秀员工作为自身价值理念的推动者，依托高科技的创新产品积极参与蓬勃发展的中国市场，把提升人类生活品质作为贯穿始终的理念。 [8]2013年，默克在上海新建的中国液晶中心开业，投资额达数千万欧元，整合了液晶混合生产、研发和营销等功能，为本地客户提供更为便捷和量身定制的服务。2014年7月23日，跨国制药与化工企业默克集团在上海重申投资中国市场，进一步加强中国在其新兴市场战略中的重要性，并宣布其在南通投资6.5亿元人民币新建的制药厂于8月份破土动工。 [9]新工厂预计2016年竣工，2017年正式投产，成为默克集团全球第二大制药厂。该厂主要用于批量生产和包装治疗糖尿病、心血管疾病和甲状腺功能失调的格华止、康忻和优甲乐产品。这些产品均被纳入了国家基本药物目录，这使默克成为首家也是唯一在华大规模新设投资生产基药目录中药物的跨国药企。 [9]除了投资药物生产，默克也拓展了其为生物医药研发客户的服务。默克密理博生命科学事业部近期的投资包括在上海张江高科技园区设立的生物制药技术培训中心，该中心可谓中国市场生物制药客户提供技术支持、培训、验证等全方位服务。 [9]默克在中国的历史1888年，德国化学家、默克工厂运营主威利·默克（Willy Merck）来到中国；1931年，上海的Schmidt公司成为默克公司在华南地区的商业代理。 [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药中国研发中心。 [23]2011年，默克在上海设立液晶应用实验室。 [24]2013年3月，默克雪兰诺宣布与百时美施贵宝携手开展格华止®战略合作； [10]2013年，默克液晶中心在上海成立。 [25]2013年12月，默克液晶中国中心在上海金桥正式开业，为中国提供中国制造的高品质液晶 [11]2014年5月，默克成功收购安智电子材料，包括其在上海的子公司与在苏州的工厂 [12]2014年，默克制药工厂在江苏南通动工。 [26]2016年，默克南通制药工厂落成， [27]默克南通生命科学中心一期项目启动 [28]；默克显示材料研发中心在上海开业。 [29]2017年，默克颜料与功能性技术应用中国中心在上海成立 [30]；默克End-to-End生物工艺开发中心在中国开业 [31]；默克光刻材料研发中国中心在苏州成立。 [32]2018年，默克迎来350周年庆典 [33]2018年2月，默克宣布设立中国创新中心 [34]2018年6月，OLED技术中心投入运营 [35]2018年7月，默克宣布与西安杨森合作共同推出2型糖尿病新药 [36]2018年9月，中国首个Mobius®一次性技术产品生产基地在无锡成立 [37]2018年12月，默克SAFC®上游技术研发中心在上海启用 [38]2019年5月，默克上海办公室乔迁 [39]2019年9月，默克携手阿里巴巴设立官方旗舰店 [40]并完成对Intermolecular公司的收购 [41]2019年10月，默克中国创新中心在上海正式开幕默克中国种子基金设立 [42]；默克完成对Versum公司的收购 [43]2019年11月，默克广东创新中心正式开幕 [44]2020年3月，默克医药经营（江苏）有限公司正式投入运营 [45]2020年5月，默克生命科学成都配送中心正式启用 [46]2020年7月，默克生命科学技术与培训中心在上海启用 [47]2020年11月，默克正式启用中文品牌标志 [48]2021年3月，默克旗下高性能材料业务正式更名为默克电子科技 [49]2021年7月，默克携生命科学、电子科技和创新中心相关的产品和解决方案亮相2021世界人工智能大会 [50]2021年10月，默克抗高血压新型药物比索洛尔氨氯地平片在中国正式上市 [51]2021年10月，默克与生物谷（北京）科技有限公司合作打造生物科技公共研发平台 [52]2021年10月，默克默克上海创新基地在浦东张江投入运营。上海创新基地占地面积2000平方米，是默克在全球建立的首个面向初创企业开放的创新平台。 [53]2023年12月8日，默克宣布，中国国家药品监督管理局正式批准拓得康®（盐酸特泊替尼片）用于治疗携带间质上皮转化因子（MET）外显子14跳跃突变的局部晚期或转移性非小细胞肺癌（NSCLC）成人患者。 [73]默克在华八十周年2013年，默克中国迎来了八十周年华诞。默克在华的两大业务分支默克雪兰诺及默克化工纷纷通过一系列庆祝活动共贺默克八十华彩。默克在华八十周年以“八十华彩历久弥新”为主题，展现该集团在华八十年的历史、成就和贡献，并表达了集团对未来的畅想：默克追求创新的脚步永不停歇。默克在华八十周年庆典，既是对历史的回顾与致敬，更是面向未来的展望与迈进。该集团正积极参与着蓬勃发展的中国市场，与2,000多名优秀员工一起携手为中国提供品质卓越的高科技创新产品。该集团旗下的两大分支－默克化工与默克雪兰诺继续齐心协力，与中国市场共同腾飞。默克雪兰诺中国在中国，默克雪兰诺拥有员工超过1000人，业务遍及全国，在中国主要经营8大领域14种药品。默克雪兰诺在生殖和甲状腺治疗领域首屈一指，在心血管、内分泌、肿瘤 [1]以及糖尿病领域也处于行业领先地位。 [13]研发创新2009年11月23日，默克雪兰诺中国研发中心在北京成立 [1]，占地总面积1,000余平方米，也是该集团全球的四大研发中心之一，该配有先进的生物医学科研仪器设备、数据库等科技资源信息科技能力。除北京外，中国研发心中心在广州和上海也有员工。默克中国研发中心注重与国内知名的科学家、临床专家充分的学术交流。2009年至2011年间，默克雪兰诺投资600万人民币用以支持开展中国生物制品技术管理人力资源合作项目。 [2]主要产品（国内） [1]治疗不孕症的果纳芬®生殖产品乐芮®、艾泽®、思则凯®和雪诺同®抗肿瘤药爱必妥®抗高血压药物康忻®治疗心绞痛药物喜格迈®治疗消化道急症的药物思他宁®治疗甲状腺功能减退症的优甲乐®及治疗甲状腺功能亢进症的赛治®治疗糖尿病的药物格华止®BH4缺乏症替代治疗用药科望®抗过敏药物阿罗格®治疗携带间质上皮转化因子拓得康®默克化工中国默克化工隶属于默克集团，自1933年，在上海开设了第一家中国子公司，赵赋斯默克化工中国董事总经理经过80年的发展，现已拥有六家子公司业务覆盖全国十八个城市，员工超过700名。在1998年默克化工便成立了默克珠光颜料与化妆品应用实验室。2007年效果颜料实验室迁址至松江基地，并更名为客户技术支持中心，实现了对默克化工旗下所有产品提供技术支持服务。除了先进的技术设备之外，那里还集中了一大批专业技术人员。客户技术支持中心在默克化工中国乃至默克全球的业务发展中都发挥着至关重要的作用。 [14]2011年，默克以100%的股份全额收购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国生物制药行业领先的细胞培养基产品和相关技术服务以及生物反应器的供应商。收购清大天一后，默克密理博的过程解决方案部门能够支持中国客户进行安全、有效的生物医药制造。默克化工主要生产效果颜料产品、实验室分析试剂、液晶材料等。消费者常见的液晶电视、笔记本电脑、手机显示屏、化妆品原料的IR3535驱蚊剂等都是出自该公司。 [1]2024年2月2日，默克宣布旗下肺癌靶向药物拓得康®（盐酸特泊替尼片）在中国商业化上市，正式向全国各家医院和药房供药。 [75]企业责任播报编辑全球项目2007年，默克集团与世界卫生组织合作共同抵抗非洲学校儿童感染的血吸虫病。血吸虫病是非洲最普遍的仅次于疟疾的热带疾病，感染群体主要为儿童。在此项合作中，默克十年以来一共捐赠含活性吡喹酮的Cesol®600药品达2亿片之多，总价值约8千万美元，可供两千七百万儿童的治疗使用。默克独家支持“全球医药健康基金会”，该项目旨在推广并使用默克的Minilab，遏制假药在全球范围内的传播。默克的移动实验室可迅速对药物进行测试，现已有570个类似的实验室在余80个国家投入使用。此外，默克还积极促进文化交流，支持助公司音乐大使德国默克爱乐乐团，定期在欧洲、亚洲和和拉丁美洲进行巡回演出。中国项目在中国，默克在取得商业成功的同时积极履行企业社会责任，开展了健康、教育和人道主义救援等领域的公益项目。默克雪兰诺：在健康领域，自2009年起，默克开展了中国甲状腺疾病健康教育项目，在国际甲状腺周期间向公众提供免费检测和义诊活动。同时，默克与北京市红十字基金会合作共同启动爱必妥®慈善援助项目 [15]，旨在帮助已确认在爱必妥®治疗中明显获益的经济困难的晚期结直肠癌患者，使其获得生命延长，并帮助部分患者获得治愈的机会。在教育领域，默克雪兰诺于2010年宣布投入600万元人民币，在全国12个城市的20所医药院校，设立资助贫困医科低年级大学生的“默克雪兰诺企业社会责任基金励学金”和奖励优秀高年级学生的“默克雪兰诺中国精英奖学金”。在人道主义救援领域，默克雪兰诺和员工在2008年为四川汶川地震共同捐赠1百多万元人民币；2010年，“默克雪兰诺企业社会责任基金”援助西南旱灾和玉树地震灾区，捐出善款20万元人民币。默克化工：2007年5月，默克化工中国向中国国家纳米科学中心捐赠科研用实验室试剂，旨在进一步促进和推动双方科研的长期合作，为中国科研事业的长足发展吸引更多的力量。2008年5月，默克化工中国携手其它国际化工公司，在北京共同签署了由国际化学品制造商协会赞助的“责任关怀北京宣言”，致力于“责任关怀”项目在中国的支持和实践。通过这项国际志愿发起活动，化工行业相互协作持续努力提高国内健康、安全和环境方面的表现。2012年，默克中国在上海5所小学开展了“默克中国校园净水项目 [16]”，是默克中国开展的第一个本地社会责任项目，通过捐赠硬件设施、开展志愿者环保课堂，旨在改善学校水质量，尤其是外来务工人员子女就读学校的水质量，并提高学生环保意识。2014年，默克化工中国成为创行中国的战略合作伙伴，默克通过创行这个平台，推动本地社会责任项目发展，支持创行学生团队的公益项目。 [17]默克化工中国连续三年参加在上海张江高科技园区举行的“张江乐跑 [18]”活动，并向赛事合作方上海国际社区中心旗下的两个主题慈善活动Giving Tree 和River of the Heart捐款，为推进中国环境保护做贡献。默克“绿晶”项目是由默克电子科技业务中国区于2017年发起的企业社会责任项目，在宣传智能设备环保使用的同时，关注中国西部偏远地区的基础教育。 [54]2018年，默克携手壹基金，全方位支持农村学校饮用水改善项目“净水计划”。从2018年起，默克中国的每名员工都将响应壹基金人人公益的号召，每天捐出一元钱人民币投入“净水计划”。同时，默克中国还将为“净水计划”提供水质检测设备及技术支持，和壹基金一起在农村地区水质快速分析与检测方面合作。此外，默克也将借助壹基金这个项目的广大平台，为农村地区疾病教育做出贡献。 [55]新手上路成长任务编辑入门编辑规则本人编辑我有疑问内容质疑在线客服官方贴吧意见反馈投诉建议举报不良信息未通过词条申诉投诉侵权信息封禁查询与解封©2024 Baidu 使用百度前必读 | 百科协议 | 隐私政策 | 百度百科合作平台 | 京ICP证030173号京公网安备110000020000

MECK_百度百科

_百度百科网页新闻贴吧知道网盘图片视频地图文库资讯采购百科百度首页登录注册进入词条全站搜索帮助首页秒懂百科特色百科知识专题加入百科百科团队权威合作下载百科APP个人中心收藏查看我的收藏0有用+10MECK播报讨论上传视频品牌本词条缺少概述图，补充相关内容使词条更完整，还能快速升级，赶紧来编辑吧！MECK，是长沙市滑板之家体育用品有限公司旗下品牌， [1]MECK品牌诞生于德国拜仁，由Julienne Meck在自家车库创建并手工制作第一块MECK滑雪单板， [2]是一个专做单板滑雪的运动品牌，主营业务是滑雪单板，陆地冲浪板，滑雪服等运动器材。 [2]外文名MECK所属公司长沙市滑板之家体育用品有限公司商标注册号44770608 [1]国际分类28 [1]目录1品牌发展2产品及服务3品牌价值观4品牌故事5制作工艺品牌发展播报编辑1998年3月，建立工厂，同年9月发布第一款MECK单板滑雪单板板；2000年9月，品牌发布MECK滑雪板产品第二代；2005年1月，MECK建立独立生产线； [2]2018年3月，推出全新工艺聚氨酯防撞边墙，比传统abs边墙耐撞度高8倍； [2]2020年1月，进入中国市场； [2]2021年3月，推出陆地冲浪板支线。2021年9月，推出全新产品两用型单板快穿固定器以及快穿雪鞋。 [2]产品及服务播报编辑单板滑雪类：MECK滑雪单板，单板快穿固定器，滑雪鞋，滑雪板包，滑雪装备包。滑板类：meck陆地冲浪板 [2]品牌价值观播报编辑创新、实践、挑战、分享 [2]品牌故事播报编辑MECK从公司成立第一天起，就全心投入产品的开发与研究。随着时间的过程不断发展和创新，生产了许多富有科技及个性的单板产品，现在MECK品牌不仅拥有独立的生产线以及生产技术，再研发和制造过程中，不断完善产品、创新以确保满足客户需求。2020年初进入中国市场，MECK一直为推动滑雪运动和支持单板滑手做出极大的贡献。品牌一直专注于创新设计和提高产品的性价比，让更多人能够接触并爱上单板滑雪这项运动。 [2]制作工艺播报编辑单板采用聚氨酯防撞边墙工艺，是一种有弹性的pu材质，耐撞性是普通abs边墙的8倍，pu边墙的唯一缺点是不够光滑，所以边墙看上去比较朴实无华。 [2]新手上路成长任务编辑入门编辑规则本人编辑我有疑问内容质疑在线客服官方贴吧意见反馈投诉建议举报不良信息未通过词条申诉投诉侵权信息封禁查询与解封©2024 Baidu 使用百度前必读 | 百科协议 | 隐私政策 | 百度百科合作平台 | 京ICP证030173号京公网安备110000020000

Meck是什么意思_Meck的翻译_音标_读音_用法_例句_爱词霸在线词典

是什么意思_Meck的翻译_音标_读音_用法_例句_爱词霸在线词典首页翻译背单词写作校对词霸下载用户反馈专栏平台登录Meck是什么意思_Meck用英语怎么说_Meck的翻译_Meck翻译成_Meck的中文意思_Meck怎么读,Meck的读音,Meck的用法,Meck的例句翻译人工翻译试试人工翻译翻译全文Meck释义[人名] 梅克点击人工翻译，了解更多人工释义实用场景例句全部A letter from Nadyezhda von Meck written in a tone she had never before used.娜蒂契达·冯·梅克用她从未用过的语气给他写了一封信.互联网收起实用场景例句释义实用场

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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