AZD-9291_MS_12364_MedChemExpress
AZD-9291_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:AZD–9291 is a third generation irreversible EGFR tyrosine kinase inhibitor with selectivity against mutant versus wild–type forms of EGFR , shows an apparent IC 50 of 12 nM against L858R and 1 nM against L858R/T790M in EGFR recombinant enzyme assay.IC50 & Target: IC50: 1 nM (EGFR L858R/T790M ), 12 nM (EGFR L858R )[1]In Vitro: AZD–9291 (AZD9291) shows similar potency to early generation tyrosine kinase inhibitor (TKIs) in inhibiting EGFRphosphorylation in EGFR cells harboring sensitising EGFR mutants including PC–9 (ex19del), H3255 (L858R) and H1650 (ex19del),with mean IC 50 values ranging from 13 to 54 nM for AZD–9291. AZD–9291 also potently inhibits phosphorylation of EGFR in T790M mutant cell lines (H1975 (L858R/T790M), PC–9VanR (ex19del/T790M), with mean IC 50 potency less than 15 nM [1].In Vivo: The tumor–bearing mice are treated with AZD–9291 (5 mg/kg/day) for one to two weeks. Within days of treatment, 5 of 5C/L858R mice displays nearly 80% reduction in tumor volume by magnetic resonance imaging MRI after therapy with AZD–9291,while 5 of 5 mice treated with vehicle shows tumor growth [1]. AZD–9291 demonstrates improved rat PK, reduced hERG affinity, and improved IGF1R margins relative to the previously described compounds, and so this compound is selected for furtherinvestigation. AZD–9291 also offers an additional degree of broader chemical and profile diversity when compared to thepreviously described lead compounds. Upon dosing AZD–9291 in three efficacy models, The comparable efficacy is observed at relatively low doses (10 mg/kg per day). The excellent efficacy is also observed when AZD–9291 is dosed at 5 mg/kg per day [2].PROTOCOL (Extracted from published papers and Only for reference)Cell Assay: AZD–9291 is dissolved in DMSO and stored, and then diluted with appropriate medium before use [1]. [1]PC–9 cells are seeded into T75 flasks (5×105 cells/flask) in RPMI growth media and incubated at 37°C, 5% CO 2. The following day the media is replaced with media supplemented with a concentration of EGFR inhibitor equal to the EC 50 concentration predetermined in PC–9cells. Media changes are carried out every 2–3 days and resistant clones allowed to grow to 80% confluency prior to the cells being trypsinised and reseeded at the original seeding density in media containing twice the concentration of EGFR inhibitor. Doseescalations are continued until a final concentration of 1.5 μM Gefitinib, 1.5 μM Afatinib, 1.5 μM WZ4002 or 160 nM AZD–9291 are achieved [1].Animal Administration: AZD–9291 is suspended in 1% Polysorbate 80 (Mice)[1].AZD–9291 is suspended in 0.5% w/v HPMC/0.1% w/v Tween in deionized water at a concentration of 20 mg/mL (Rat)[2]. [1][2]Mice [1]The EGFR L858R and EGFR L858R+T790M mice (male and female) are used. AZD–9291 is suspended in 1% Polysorbate 80 and administered via oral gavage once daily at the doses of 7.5 mg/kg and 5 mg/kg, respectively. Mice are imaged weekly at theVanderbilt University Institute of Imaging Science. For immunoblot analysis, mice are treated for eight hours with drug as described before dissection and flash freezing of the lungs. Lungs are pulverized in liquid nitrogen before lysis.Rat [2]Product Name:AZD–9291Cat. No.:HY-15772CAS No.:1421373-65-0Molecular Formula:C 28H 33N 7O 2Molecular Weight:499.61Target:EGFR; EGFR Pathway:JAK/STAT Signaling; Protein Tyrosine Kinase/RTK Solubility:DMSO: ≥ 30 mg/mLThe male RccHan:WIST rats (10–week–old) are received a single oral dose of AZD–9291 (200 mg/kg). Blood glucose levels are measured using an Accuchek Active meter. Serum insulin concentrations are determined using a commercial rat ELISA kit.References:[1]. Cross DA, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M–mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep; 4(9):1046–61.[2]. Finlay MR, et al. Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistancemutations that spares the wild type form of the receptor. J Med Chem. 2014 Oct 23;57(20):8249–67.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
赛普替尼 分子量
赛普替尼（Selpercatinib），其化学名为LOXO-292，是一种选择性RET抑制剂，用于治疗RET融合阳性的非小细胞肺癌和甲状腺癌等类型的癌症。
赛普替尼的分子式为C29H31N7O3，根据分子式计算其分子量如下：
碳（C）的原子量约为12.01，因此C29 = 29 * 12.01
氢（H）的原子量约为1.008，因此H31 = 31 * 1.008
氮（N）的原子量约为14.01，因此N7 = 7 * 14.01
氧（O）的原子量约为16.00，因此O3 = 3 * 16.00
分子量的计算公式为：
分子量= (C的数量×C的原子量) + (H的数量×H的原子量) + (N的数量×N的原子量) + (O的数量×O的原子量)
将上述数值代入计算：
分子量= (29 ×12.01) + (31 ×1.008) + (7 ×14.01) + (3 ×16.00)
分子量≈348.29 + 31.248 + 98.07 + 48.00
分子量≈525.608
所以，赛普替尼的分子量大约是525.61 g/mol。
这个计算是基于分子式中每种元素的原子量的标准值，实际分子量可能会有极小的变化，这取决于原子量的精确值。
法瑞西单抗结构式__理论说明
法瑞西单抗结构式理论说明1. 引言1.1 概述法瑞西单抗是一种重要的抗体药物，它具有广泛的应用领域，特别是在治疗癌症和免疫相关性疾病方面。
其强大的抗肿瘤活性和较低的毒副作用使得法瑞西单抗成为临床上备受关注的药物之一。
本文将对法瑞西单抗的结构式进行理论说明，深入探讨其分子组成、工作原理以及结构与功能之间的关系。
1.2 文章结构本文分为五个主要部分。
首先是引言部分，介绍文章的背景和目的。
接下来是法瑞西单抗结构式部分，详细展示了该药物的简介、结构示意图以及其分子组成和元素分析结果。
随后是理论说明部分，揭示了法瑞西单抗的工作原理、剂量和用途以及结构与功能之间的关系。
然后是实际应用和临床研究进展部分，探讨了法瑞西单抗在治疗癌症和免疫相关性疾病中的应用情况，并展望了其研究进展和未来发展方向。
最后是结论部分，总结了本文的重点观点并对未来的发展进行展望。
1.3 目的本文的目的是对法瑞西单抗的结构式进行理论说明，从而深入了解该药物在治疗癌症和免疫相关性疾病中的应用机制。
通过对其工作原理、剂量和用途以及结构与功能之间关系的探讨，旨在为读者提供全面而深入的认识，促进对该药物的应用和研究进展有更深入的理解。
同时，本文也将展望法瑞西单抗未来发展的方向，为相关领域的科学家和医学专业人士提供借鉴和指导。
2. 法瑞西单抗结构式2.1 法瑞西单抗简介法瑞西单抗是一种单克隆抗体，也被称为贝伐珠单抗或贝妥替尼。
它是通过针对人类的癌细胞表面标记物进行计算机模拟和分子筛选得到的。
法瑞西单抗具有高度特异性，能够选择性地与靶标癌细胞结合，从而阻断其增殖和扩散。
2.2 结构示意图法瑞西单抗的化学结构由一条重链和一条轻链组成。
它们之间通过二硫键相连接，并形成一个Y形的分子结构。
每条链上都含有不同类型的氨基酸序列。
在法瑞西单抗的重链上，有一个可变区和一个恒定区。
可变区包含了决定该抗体特异性的亚变区（VH）和衍生自个体基因库的多样化亚变区（DH）。
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HY-K0011Protease Inhibitor Cocktail, mini-Tablet (EDTA-Free)用于细胞裂解与组织抽提，片剂更便于使用。
HY-K0021Phosphatase Inhibitor Cocktail I (100X in DMSO)有效抑制碱性、丝氨酸/苏氨酸磷酸酶。
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AZD9291中文说明书
【研发名】AZD9291【药物名】Osimertinib【商品名】Tagrisso【美国上市时间】非小细胞肺癌，2015年11月13日【类别】抑制剂【靶点】EGFR【分子结构】化学式：CH33N7O2•CH4O3S分子式：28N-(2-{2dimethylaminoethyl-methylamino}-4-methoxy-5-{[4-(1-methylindol -3-yl)pyrimidin-2yl]amino}phenyl)prop-2-enamide mesylate salt分子结构：分子量：596 g/mol【生产公司】AstraZeneca Pharmaceuticals 阿斯利康【购买地】美国【剂型和规格】口服片剂，两种剂量：80mg和40mg。
80 mg 药片：米色，椭圆形和双凸片在一侧标记有“AZ 80”和反面平坦和可得到30片瓶(NDC 0310-1350-30)。
40 mg 药片：米色，圆和双凸片在一侧标记有“AZ 40”和反面平坦和可得到20片瓶(NDC 0310-1349-30)。
【本质】AZD9291含40或80 mg Osimertinib，分别等同于47.7和95.4 mg Osimertinib 甲磺酸盐。
在片芯中无活性成分是甘露醇，微晶纤维素，低取代羟丙基纤维素和硬脂酰富马酸钠。
片涂层由聚乙烯醇，二氧化钛，聚乙二醇3350，滑石，氧化铁黄，氧化铁红和氧化铁黑组成。
【作用机理】AZD9291是表皮生长因子受体(EGFR)的激酶抑制剂，可逆性结合EGFR(T790M，L858R和外显子19缺失)。
在培养细胞中和动物肿瘤移植模型，AZD9291表现出对NSCLC系窝藏EGFR突变(T790M/L858R，L858R，T790M/外显子19缺失，和外显子19缺失)和，至较低程度，野生型EGFR扩增抗肿瘤活性。
在AZD9291口服给药后血浆中曾被鉴定出两种活性代谢物(AZ7550和AZ5104)与AZD9291有相似抑制性。
澳洲茄胺盐酸盐注射剂对小鼠Lewis肺癌抑瘤作用研究
收 稿 日期 ：０ ０１ －０ ２ １ ． ２ ２ 基 金 项 目 ： 怡 康 纳 制 药 中药 研 发 基 金 项 目（ Ｙ ４ ３ １ ． 卓 Ｚ ０００ ）
作者简介 ： 李富仁（ ９ ６一）， ， １５ 男 副教授 ， 主要从事药物作用机制研究
第 １ 期
李 富仁 ， ： 等 澳洲茄胺盐 酸盐注射剂对小 鼠 Ｌ ｗｓ ｅ ｉ肺癌抑瘤作用研究
ｉ ｅｔ ｎｏ ｕｅＬｗ ｓ ｕ ｇｃｒｉ ｍ ．Ｍｅｈ ｄ Ｔ ｅｓ ｄ ｎ ａｅ ｂｅ ｅｔｅｄｕ ｆ ｃ ｙｍ ａｓ ｎ ｃ ｏ ｆ ｊ ｉ ｍｏｓ ｅ ｉ ｌｎ ａｃ ｏ ａ ｎ ｔｏ ｓ ｈ ｔ ｙｉ ｅｇｇｄｔ ｏ ｓｒ ｒｇｅ ｅｔ ｂ ｅｌ ｕ ｓ ｏ ｖ ｈ ｆ ｓ ｌ
无 菌条 件 下 解 剖 Ｌ ｗｓ肺癌 Ｃ ７ Ｌ ６荷瘤 小 ｅ ｉ ５Ｂ ／
鼠（ 由吉林 省肿 瘤研 究所 提 供 ） 取瘤 块 ， ， 除去 坏死
组织 ， 个瘤 块混 合 剪 成 小 块 ， 置 ９ｃ 平 皿 内 ， 数 放 ｍ 用玻 璃注 射器 芯研磨 ， 匀后用 １０目不 锈钢 网筛 磨 ０
GeXP简介
•Alignment
•Call scores
•Heterozygote Detection
2013/11/12
6
GeXP荧光系统
•GeXP更适合检测突变/杂合子： •波长越长，干扰越少 ，背景噪音低;
•650nm •laser •750nm •laser
•无10％的cut off把噪音，不会把10％以上杂合子去掉；
•NO Interference •from biological materials
7
个体化用药检测
KIT-Exon9
PDGFRA-exon12
EGFR突变检测
肿瘤药物对应相关基因的检测
药物名称 易瑞沙/特罗凯类 检测基因
EGFR-Exon18 突变 EGFR-Exon19 突变 EGFR-Exon21 突变 EGFR-Exon20突变 C-KIT-Exon9 突变 C-KIT-Exon11 突变 C-KIT-Exon13 突变 C-KIT-Exon17 突变 PDGFRα-Exon12 PDGFRα-Exon18 CYP2D6*10 多态性 XRCC1-Exon6 多态性 XRCC1-Exon10 多态性 ERCC1-codon118 多态性 MRP2-Exon10 多态性 BRCA1-Exon2 (女)多态性 BRCA1-Exon20 (女)多态性 XPD基因多态性 UGT1A1 *6 多态性 UGT1A1*28 多态性 DPYD*2A 多态性
伊马替尼 他莫昔芬
铂类
伊立替康 氟脲嘧啶类
HBV分型、耐药突变检测
2、片段分析
• 只需要研究长度，不需要知道具体序列 • 分别率为1bp
片段分析应用
STR/SSR
融合基因，可变剪切体
GC测定盐酸普拉克索中三乙胺残留量
基于真实世界数据的西妥昔单抗临床综合评价
临床药学㊀基金项目:山东省医学会临床药学应用研究项目(Ｎｏ.ＹＸＨ２０１９ＺＸ００９)ꎻ山东省第一批药品临床综合评价项目(Ｎｏ.２０２１ＹＺ０１２)作者简介:栾亚丽ꎬ女ꎬ主管药师ꎬ研究方向:医院药事管理与药学服务ꎬＥ－ｍａｉｌ:ｓｌｙｙｌｙｌ１２０９＠１６３.ｃｏｍ通信作者:王晓君ꎬ女ꎬ主管药师ꎬ研究方向:医院药品管理ꎬＴｅｌ:０５３１－６８７７９０８０ꎬＥ－ｍａｉｌ:ｗａｎｇｘｉａｏｊｕｎ＿９＠１６３.ｃｏｍ基于真实世界数据的西妥昔单抗临床综合评价栾亚丽１ꎬ王元明２ꎬ高田田１ꎬ王晓君１(１.山东第一医科大学附属省立医院药学部ꎬ山东济南２５００１２ꎻ２.山东省药师协会ꎬ山东济南２５０１０１)摘要:目的㊀基于真实世界数据对西妥昔单抗开展临床综合评价ꎬ拟为临床合理使用及药品相关决策提供依据ꎮ方法㊀参考药品临床综合评价相关指南ꎬ基于真实世界数据ꎬ从安全性㊁有效性㊁经济性㊁创新性㊁适宜性㊁可及性６个维度对西妥昔单抗进行评价ꎮ结果㊀安全性ꎬ西妥昔单抗的多数不良反应与贝伐珠单抗㊁传统化疗方案无显著性差异ꎬ但皮疹发生率显著高于其他两种方案ꎻ有效性ꎬ西妥昔单抗与贝伐珠单抗无显著性差异ꎬ但５％的缓解率远低于临床试验结果ꎻ经济性ꎬ进行倾向值得分匹配后ꎬ应用西妥昔单抗与应用贝伐珠单抗方案的总费用无显著性差异ꎬ但显著高于传统化疗方案总费用ꎻ创新性ꎬ西妥昔单抗可用于头颈部鳞癌ꎬ填补了该领域临床治疗空白ꎬ满足了临床需求ꎬ具有一定的创新性ꎻ适宜性ꎬ非劣性ꎻ可及性ꎬ当前在山东地区的可获得性和可负担性相对较差ꎮ结论㊀与贝伐珠单抗相比较ꎬ西妥昔单抗在安全性㊁有效性㊁经济性㊁适宜性无显著性差异ꎬ创新性有优势ꎬ可及性略差ꎮ关键词:药品临床综合评价ꎻ结直肠癌ꎻ西妥昔单抗ꎻ真实世界数据中图分类号:Ｒ９５㊀文献标志码:Ａ㊀文章编号:２０９５－５３７５(２０２４)０４－０３９６－０６ｄｏｉ:１０.１３５０６/ｊ.ｃｎｋｉ.ｊｐｒ.２０２４.０４.０１５Ｃｌｉｎｉｃａｌａｐｐｌｉｃａｔｉｏｎｅｖａｌｕａｔｉｏｎｏｆｃｅｔｕｘｉｍａｂｂａｓｅｄｏｎｒｅａｌ－ｗｏｒｌｄｄａｔａＬＵＡＮＹａｌｉ１ꎬＷＡＮＧＹｕａｎｍｉｎｇ２ꎬＧＡＯＴｉａｎｔｉａｎ１ꎬＷＡＮＧＸｉａｏｊｕｎ１(１.ＤｅｐａｒｔｍｅｎｔｏｆＰｈａｒｍａｃｙꎬＳｈａｎｄｏｎｇＰｒｏｖｉｎｃｉａｌＨｏｓｐｉｔａｌＡｆｆｉｌｉａｔｅｄｔｏＳｈａｎｄｏｎｇＦｉｒｓｔＭｅｄｉｃａｌＵｎｉｖｅｒｓｉｔｙꎬＪｉｎａｎ２５００１２ꎬＣｈｉｎａꎻ２.ＳｈａｎｄｏｎｇＰｈａｒｍａｃｉｓｔｓＡｓｓｏｃｉａｔｉｏｎꎬＪｉｎａｎ２５０１０１ꎬＣｈｉｎａ)Ａｂｓｔｒａｃｔ:Ｏｂｊｅｃｔｉｖｅ㊀Ｔｏｃｏｎｄｕｃｔａｃｌｉｎｉｃａｌａｐｐｌｉｃａｔｉｏｎｅｖａｌｕａｔｉｏｎｏｆｃｅｔｕｘｉｍａｂｂａｓｅｄｏｎｒｅａｌ－ｗｏｒｌｄｄａｔａꎬｅｘｐｌｏｒｅｔｈｅｃｏｎｔｅｎｔａｎｄｍｅｔｈｏｄｓｏｆｔｈｅｃｌｉｎｉｃａｌｃｏｍｐｒｅｈｅｎｓｉｖｅｅｖａｌｕａｔｉｏｎｏｆａｎｔｉｔｕｍｏｒｄｒｕｇｓꎬａｎｄｐｒｏｖｉｄｅａｂａｓｉｓｆｏｒｒａｔｉｏｎａｌｃｌｉｎｉｃａｌｕｓｅａｎｄｄｒｕｇ－ｒｅｌａｔｅｄｄｅｃｉｓｉｏｎ－ｍａｋｉｎｇ.Ｍｅｔｈｏｄｓ㊀Ａｃｃｏｒｄｉｎｇｔｏｔｈｅｇｕｉｄｅｌｉｎｅｓｏｆｃｌｉｎｉｃａｌａｐｐｌｉｃａｔｉｏｎｅｖａｌｕａｔｉｏｎꎬｃｅｔｕｘｉｍａｂｗａｓｅｖａｌｕａｔｅｄｉｎｓｉｘｄｉｍｅｎｓｉｏｎｓｂａｓｅｄｏｎｒｅａｌ－ｗｏｒｌｄｄａｔａ.Ｒｅｓｕｌｔｓ㊀Ｔｈｅｅｖａｌｕａｔｉｏｎｒｅｓｕｌｔｓｏｆｖａｒｉｏｕｓｄｉｍｅｎｓｉｏｎｓｓｈｏｗｅｄｔｈａｔｍｏｓｔａｄｖｅｒｓｅｒｅａｃｔｉｏｎｓｏｆｃｅｔｕｘｉｍａｂｗｅｒｅｎｏｔｓｉｇｎｉｆｉｃａｎｔｌｙｄｉｆｆｅｒｅｎｔｆｒｏｍｂｅｖａｃｉｚｕｍａｂａｎｄｃｏｍｍｏｎｃｈｅｍｏｔｈｅｒａｐｙｒｅｇｉｍｅｎｓꎬｂｕｔｔｈｅｉｎｃｉｄｅｎｃｅｏｆｒａｓｈｗａｓｓｉｇｎｉｆｉｃａｎｔｌｙｈｉｇｈｅｒｔｈａｎｔｈｅｏｔｈｅｒｓ.Ｉｎｔｅｒｍｓｏｆｅｆｆｉｃａｃｙꎬｔｈｅｒｅｉｓｎｏｓｉｇｎｉｆｉｃａｎｔｄｉｆｆｅｒｅｎｃｅｂｅ￣ｔｗｅｅｎｃｅｔｕｘｉｍａｂａｎｄｂｅｖａｃｉｚｕｍａｂꎬｂｕｔｔｈｅｒｅｍｉｓｓｉｏｎｒａｔｅｏｆ５％ｉｓｍｕｃｈｌｏｗｅｒｔｈａｎｔｈｅｃｌｉｎｉｃａｌｔｒｉａｌｒｅｓｕｌｔｓ.Ａｆｔｅｒｐｒｏｐｅｎｓｉｔｙｓｃｏｒｅｍａｔｃｈｉｎｇꎬｔｈｅｒｅｗａｓｎｏｓｉｇｎｉｆｉｃａｎｔｄｉｆｆｅｒｅｎｃｅｉｎｔｈｅｔｏｔａｌｃｏｓｔｏｆｔｈｅｂｅｖａｃｉｚｕｍａｂｒｅｇｉｍｅｎꎬｂｕｔｉｔｗａｓｓｉｇｎｉｆｉｃａｎｔｌｙｈｉｇｈ￣ｅｒｔｈａｎｔｈｅｔｏｔａｌｃｏｓｔｏｆｔｈｅｃｏｍｍｏｎｃｈｅｍｏｔｈｅｒａｐｙｒｅｇｉｍｅｎ.Ｃｅｔｕｘｉｍａｂｃａｎｂｅｕｓｅｄｆｏｒｈｅａｄａｎｄｎｅｃｋｓｑｕａｍｏｕｓｃｅｌｌｃａｒｃｉ￣ｎｏｍａｗｈｉｃｈｃａｎｆｉｌｌｔｈｅｃｌｉｎｉｃａｌｔｒｅａｔｍｅｎｔｇａｐａｎｄｍｅｅｔｔｈｅｃｌｉｎｉｃａｌｒｅｑｕｉｒｅｍｅｎｔｓ.Ｉｔｉｓａｎａｌｏｇｏｕｓｔｏｏｔｈｅｒｓｉｍｉｌａｒａｎｔｉ－ｔｕｍｏｒｄｒｕｇｓａｎｄｈａｓｎｏｏｂｖｉｏｕｓａｄｖａｎｔａｇｅｓｏｖｅｒｔｈｅｃｕｒｒｅｎｔｓｕｉｔａｂｉｌｉｔｙꎬｂｕｔａｖａｉｌａｂｉｌｉｔｙａｎｄａｆｆｏｒｄａｂｉｌｉｔｙｏｆｃｅｔｕｘｉｍａｂｉｎＳｈａｎｄｏｎｇｉｓｒｅｌａｔｉｖｅｌｙｐｏｏｒ.Ｃｏｎｃｌｕｓｉｏｎ㊀Ｃｏｍｐａｒｅｄｗｉｔｈｂｅｖａｃｉｚｕｍａｂꎬｃｅｔｕｘｉｍａｂｈａｓｎｏｓｉｇｎｉｆｉｃａｎｔｄｉｆｆｅｒｅｎｃｅｉｎｓａｆｅｔｙꎬｅｆｆｉｃａｃｙꎬｅ￣ｃｏｎｏｍｙꎬａｎｄｓｕｉｔａｂｉｌｉｔｙꎬａｎｄｈａｓａｄｖａｎｔａｇｅｓｉｎｉｎｎｏｖａｔｉｏｎａｎｄｓｌｉｇｈｔｌｙｐｏｏｒａｃｃｅｓｓｉｂｉｌｉｔｙ.Ｋｅｙｗｏｒｄｓ:ＣｌｉｎｉｃａｌａｐｐｌｉｃａｔｉｏｎｅｖａｌｕａｔｉｏｎꎻＣｏｌｏｒｅｃｔａｌｃａｎｃｅｒꎻＣｅｔｕｘｉｍａｂꎻＲｅａｌ－ｗｏｒｌｄｄａｔａ㊀㊀国家卫生健康委«关于规范开展药品临床综合评价工作的通知»和«抗肿瘤药物临床综合评价技术指南(２０２２年版试行)»(以下简称 技术指南 )为抗肿瘤药品临床综合评价工作的开展指明了具体方法和思路[１－２]ꎮ结直肠癌是最常见的消化道肿瘤之一ꎬ发病率及死亡率均高[３－４]ꎬ近年来分子靶向药物已成为结直肠癌治疗领域研究与应用的焦点[５]ꎮ头颈部鳞状细胞癌是世界第六大常见癌症ꎬ治疗手段十分有限ꎬ总生存时间往往不足１年ꎮ西妥昔单抗一直是治疗结直肠癌的重要药物ꎬ近期又获批了头颈部鳞癌的适应证ꎬ目前我国药品临床综合评价工作结合医院患者实际使用开展评价案例较少[６－８]ꎬ尚未有研究对西妥昔单抗进行临床综合评价ꎮ本研究拟以西妥昔单抗为例ꎬ基于真实世界数据开展临床综合评价ꎬ为临床合理使用及相关决策制定提供依据ꎬ并为其他药品临床综合评价工作的开展提供借鉴ꎮ１㊀资料与方法１.１㊀数据来源㊀选择山东省三级综合性医院和肿瘤专科医院各１家ꎬ分别抽取２０１９年１月１日至２０２０年８月３１日期间应用西妥昔单抗的患者病例１０９份和１０７份ꎮ同时从综合性医院抽取了同期７９份应用贝伐珠单抗㊁以及１００份应用传统化疗方案治疗结直肠癌患者的病例ꎬ作为对照组ꎮ提取山东省药品集中采购平台２０１９年１月１日至２０１９年１２月３１日的采购配备数据ꎮ１.２㊀研究方法㊀根据«药品临床综合评价管理指南(２０２１年版试行)»(以下简称 管理指南 )ꎬ从安全性㊁有效性㊁经济性㊁创新性㊁适宜性㊁可及性６个维度开展科学规范的整合分析与综合研判ꎮ对于年龄㊁住院天数㊁住院次数等定量指标ꎬ以均值ʃ标准差描述ꎻ对于性别㊁疾病分类等计数资料用频数和百分比表示ꎮ对于安全性和有效性的指标ꎬ采用卡方检验或者Ｆｉｓｈｅｒ精确概率法进行药物间的差异性比较ꎮ采用最小成本法进行经济性评价ꎬ并利用倾向性得分匹配对年龄㊁住院时间㊁住院次数等协变量进行调整ꎮ配备率数据来源于山东省药品集中采购平台ꎬ２０１９年全国和山东省居民人均可支配收入来自国家统计局和山东省统计局公布的数据ꎮ使用ＩＢＭＳＰＳＳＳｔａｔｉｓｔｉｃｓ２６.０软件和ＳｔａｔａＭＰ１４软件进行统计分析ꎬ双侧检验水准α＝０.０５ꎬＰ<０.０５认为具有显著性差异ꎮ２㊀结果２.１㊀基于真实世界数据的临床综合评价指标体系构建情况㊀本研究根据 管理指南 建立西妥昔单抗临床综合评价指标体系ꎬ包括安全性㊁有效性㊁经济性㊁创新性㊁适宜性和可及性６个一级指标ꎬ对应的二级指标见表１ꎮ表１㊀西妥昔单抗临床综合评价指标体系一级指标二级指标安全性不良反应发生率有效性疗效评价情况分析经济性日均住院总费用创新性填补临床治疗空白ꎬ未满足的临床需求适宜性适应证㊁贮存条件和给药方式可及性配备率㊁可负担性２.２㊀基线特征㊀本研究对于安全性评价基于来自两家医院的３９５份病例的各类不良反应发生频率ꎬ患者基本信息情况见表２ꎮ两家医院患者男性数量均高于女性ꎬ平均年龄相近ꎮ平均住院天数和平均住院次数两家医院差异较大ꎬ肿瘤专科医院均远高于综合医院ꎮ表２㊀抽取的３９５份患者病历基本信息变量西妥昔单抗(ｎ＝２１６)贝伐珠单抗(ｎ＝７９)传统化疗方案(ｎ＝１００)某综合医院(ｎ＝１０９)某肿瘤专科医院(ｎ＝１０７)某综合医院某综合医院男性８１(７４.３１％)７２(６７.２９％)３９(４９.３７％)６１(６１.００％)女性２８(２５.６９％)３５(３２.７１％)４０(５０.６３％)３９(３９.００％)年龄５８.５０ʃ９.７２５９.０４ʃ１１.８４５７.９７ʃ１２.２８５８.５ʃ１０.９１住院天数３.８７ʃ２.８５１０.２０ʃ１２.２２４.００ʃ２.７５３.４２ʃ２.４６住院次数５.８３ʃ４.８１１１.９７ʃ９.０２６.６２ʃ４.３１５.２５ʃ３.２８结直肠癌１０５(９６.３３％)９８(９１.５９％)７９(１００％)１００(１００％)头颈部鳞癌４(３.６７％)９(８.４１％)０(０％)０(０％)２.３㊀安全性㊀接受３种治疗方案的３９５名患者真实世界数据中出现的不良反应分布见表３ꎮ发生率较高的不良反应有消化道反应㊁骨髓抑制㊁发热等ꎬ３组间无显著性差异ꎮ但西妥昔单抗的皮疹发生率(１０.６５％)远高于其他两种方案(０％)ꎬ具有显著性差异(Ｐ<０.０５)ꎮ２.４㊀有效性㊀考虑到采用阳性对照(头对头试验)得到的有效性结果更具说服力ꎬ目前西妥昔单抗治疗头颈部鳞癌的病例数量较少ꎬ因此有效性的分析基于同一家综合医院的１８４份结直肠癌患者数据ꎬ包括１０５名应用西妥昔单抗(未纳入４份头颈部鳞癌患者病历)和７９名应用贝伐珠单抗的患者ꎮ根据 技术指南 要求进行归类:①完全缓解ꎻ②部分缓解ꎻ③疾病稳定ꎻ④疾病进展ꎻ⑤因肿瘤致早期死亡ꎻ⑥因治疗毒性致早期死亡ꎻ⑦其他原因致早期死亡ꎻ⑧无法分类(不能评价或资料不完整)ꎮ归入４~８类的患者视为治疗无效ꎮ表３㊀３种用药方案的不良反应发生情况不良反应西妥昔单抗(ｎ＝２１６)贝伐珠单抗(ｎ＝７９)传统化疗方案(ｎ＝１００)例数发生率(％)例数发生率(％)例数发生率(％)Ｐ值消化道反应３４１５.７４１７２１.５２９９.０００.０６５骨髓抑制２９１３.４３１１１３.９２１５１５.０００.９３２发热２０９.２６１０１２.６６９９.０００.６４９皮疹２３１０.６５００.００００.００<０.００１腹泻８３.７０４５.０６００.０００.０６４胸闷２０.９３１１.２７００.０００.７７２乏力４１.８５２２.５３１１.０００.７７３失声００.００００.００１１.０００.４５３头痛３１.３９００.００１１.０００.８１６转氨酶轻度升高００.００００.００１１.０００.４５３四肢麻木１０.４６１１.２７２２.０００.３１６㊀㊀化疗周期在５~６个周期之间ꎬ疗效评价结果见表４ꎮ基于贝伐珠单抗的方案整体有效率(６８.３５％)略高于西妥昔单抗(６６.６７％)ꎬ卡方检验无统计学差异ꎮ表４㊀１８４名结直肠癌患者疗效评价分析疗效西妥昔单抗(ｎ＝１０５)贝伐珠单抗(ｎ＝７９)例数占比平均化疗周期例数占比平均化疗周期完全缓解００.０００００.０００部分缓解５４.５９４.２５５６.３３１０.００疾病稳定６５５９.６３５.２７４９６２.０３５.３９疾病进展３５３２.１１４.９２２３２９.１１５.８７因肿瘤致早期死亡００.０００１１.２７１２.００因治疗毒性致早期死亡００.０００００.０００其他原因致早期死亡００.０００００.０００无法分类００.０００１１.２７９.００有效数合计(占比)７０(６６.６７％)５４(６８.３５％)卡方统计量０.０５８Ｐ值０.４６８２.５㊀经济性㊀根据以上研究ꎬ西妥昔单抗和贝伐珠单抗治疗结直肠癌患者的疗效无统计学差异ꎬ因此采用最小成本法进行经济学评价ꎮ由于综合医院和专科医院的平均住院日差距较大ꎬ经济性分析仅基于来自综合医院的结直肠癌患者的数据ꎬ包括１０５份使用西妥昔单抗㊁７９份贝伐珠单抗和１００份未应用任何靶向药物的传统化疗患者病例ꎮ采用有放回的倾向性得分匹配法对年龄㊁住院天数㊁住院次数等变量进行调整ꎬ对各方案的费用进行比较ꎮ应用西妥昔单抗与贝伐珠单抗进行匹配分析前后结果ꎬ具体见表５㊁图１ꎻ应用西妥昔单抗与传统化疗方案进行匹配分析前后结果ꎬ具体见表６㊁图２ꎮ综合来看ꎬ无论是否对混杂因素进行匹配ꎬ西妥昔单抗对比贝伐珠单抗的费用无统计学差异ꎬ但与全身系统化疗方案相比有统计学差异ꎮ表５㊀匹配前后西妥昔单抗对比贝伐珠单抗的费用差异(单位:元)匹配前后西妥昔单抗贝伐珠单抗差异标准差Ｔ值匹配前２０６８６.４８１９３２４.６６１３６１.８３１９７５.０７０.６９匹配后２０４８５.５８２０５２１.７７－３６.２０２００１.１２－０.０２图１㊀西妥昔单抗与贝伐珠单抗倾向性得分匹配表６㊀匹配前后西妥昔单抗对比传统化疗方案的费用差异(单位:元)匹配前后西妥昔单抗传统化疗方案差异标准差Ｔ值匹配前２０６８６.４８１０６３４.９３１００５１.５５１７３３.３４５.８匹配后１９０３１.１１１１１５１.０５７８８０.０６１４２２.１５５.５４图２㊀西妥昔单抗与传统化疗方案倾向性得分匹配２.６㊀创新性㊀通过基因检测等手段找到敏感而特异的预后标志物ꎬ实现个体化治疗是临床治疗结直肠癌的一大趋势ꎬ西妥昔单抗在ＲＡＳ基因野生型患者中的优势明显ꎬ对于更加精确适应证人群的靶向治疗具有一定的创新性ꎮ此外ꎬ２０１９年４月ꎬ默克公司向国家药品监督管理局提交西妥昔单抗联合铂类化疗作为复发和/或转移性头颈部鳞癌一线治疗的注册申请ꎬ并于２０１９年８月因 具有明显治疗优势创新药 纳入优先审评程序ꎮ通过优先审评㊁审批的通道上市ꎬ体现了其创新性ꎮ头颈部鳞癌作为西妥昔单抗的新适应证ꎬ２０２０年３月在中国获批ꎬ打破了中国复发和/或转移性头颈部鳞癌患者３０年来铂类化疗效果不佳的困局ꎬ并扩大了在肿瘤人群中的应用范围ꎮ西妥昔单抗联合化疗展现出了对复发和/或转移头颈部鳞癌显著的效果[９]ꎬ填补临床治疗空白ꎬ体现出其具有一定的创新性ꎮ２.７㊀适宜性㊀通过查阅药品说明书㊁诊疗指南等资料以及访谈医护人员发现ꎬ西妥昔单抗疗效确切ꎬ适应证明确ꎬ药代动力学参数完整ꎬ用于不同适应证治疗方案的治疗剂量是统一的ꎬ便于临床医生记忆掌握ꎬ给药剂量㊁频次适宜ꎬ依从性良好ꎬ技术特点适宜性较好ꎮ从贮存条件和给药方式上来看ꎬ西妥昔单抗作为抗肿瘤注射剂ꎬ在贮存和使用方面有着较为严格的要求ꎬ其适宜性不劣于同类药品ꎮ２.８㊀可及性㊀对２０１９年的配送数据进行分析ꎬ从医院等级来看ꎬ配备西妥昔单抗的医院共６４家ꎬ其中三级医院４２家㊁二级医院２１家㊁基层医院１家ꎬ各级医院数量均普遍低于贝伐珠单抗ꎮ通过计算山东省配备该药品医院的数量与肿瘤专科医院及有肿瘤科的医院数量的占比ꎬ获得不同级别医院的西妥昔单抗和贝伐珠单抗的配备率ꎬ情况见表７ꎮ表７㊀山东省不同等级医院西妥昔单抗与贝伐珠单抗配备率医院等级西妥昔单抗贝伐珠单抗医院数量配备率(％)医院数量配备率(％)山东省的肿瘤专科医院及有肿瘤科的医院数量Ｐ值三级４２３２.０６５３４０.４６１３１０.０９９二级２１８.４７５９２３.７９２４８<０.００１基层医院１４.７６４１９.０５２１０.３４３未定级ＮＡＮＡＮＡＮＡ２２－合计６４１５.１７１１６２７.４９４２２㊀㊀由于肿瘤患者的治疗多集中在二㊁三级医院ꎬ所以西妥昔单抗㊁贝伐珠单抗的配备也主要集中在二㊁三级医院ꎬ２０１９年西妥昔单抗在二㊁三级医院的配备率分别为８.４７％和３２.０６％ꎬ均低于贝伐珠单抗(２３.７９％和４０.４６％)ꎮ各地市配备率均低于５０％ꎬ普遍低于贝伐珠单抗ꎬ可获得率相对较低ꎮ㊀㊀参照管理指南ꎬ可负担性指标建议采用人均年治疗费用占城乡居民家庭年人均可支配收入比重ꎮ由于本研究抽取的西妥昔单抗使用时间为２０１９年１月１日至２０２０年８月３１日ꎬ主要的数据分布于２０１９年ꎬ经查询ꎬ国家统计局公布的２０１９年全国和山东省居民人均可支配收入分别为３０７３３元和３１５９７元ꎮ根据文献研究结果[１０]ꎬ结直肠癌的治疗疗程平均为４.８个月(首月用药１８支ꎬ后续月份１６支)ꎬ年用量为１８支＋３.８月ˑ１６支＝７８.８支ꎮ西妥昔单抗人均年用药治疗费用＝７８.８支ˑ１２０４.３５元/支＝９４９０２.７８元ꎬ是全国居民人均可支配收入的３.０９倍ꎬ是山东省人均可支配收入的３.００倍ꎬ可负担性较差ꎮ由于各个省份的报销政策不尽相同ꎬ不同医保类型患者的报销比例也有所差别ꎬ按照综合报销比例为６５％进行粗略估计ꎬ西妥昔单抗人均年用药治疗自付费用为３３２１５.９７元ꎬ分别是全国和山东省居民人均可支配收入的１.０８倍和１.０５倍ꎮ从计算结果来看ꎬ患者的西妥昔单抗治疗可负担性一般ꎬ说明肿瘤患者的治疗负担仍相对较重ꎮ３㊀讨论本研究发现在真实世界应用中ꎬ西妥昔单抗常见的不良反应为消化道反应㊁骨髓抑制㊁发热等ꎻ既往的临床试验中[９ꎬ１１－１４]ꎬ西妥昔单抗最常见的不良反应为中性粒细胞减少症㊁腹泻㊁皮疹和甲沟炎等ꎬ真实世界数据与临床试验结果相似ꎮ另外考虑本研究为回顾性研究ꎬ症状轻微㊁没有对症治疗等病历中未记录不良反应的无法统计到ꎬ因此安全性评价方面ꎬ不良反应发生率可能会低于实际情况ꎮ既往多项临床实验证明了西妥昔单抗的有效性[９ꎬ１１－１５]ꎬ特别是在ＲＡＳ基因野生型的优势明显ꎬＴＡＩＬＯＲ研究早期的数据显示ꎬ西妥昔单抗联合ＦＯＬ￣ＦＯＸ－４ꎬ能够显著提高中国ＲＡＳ野生型ｍＣＲＣ患者的无进展生存期(９.２个月对比７.４个月)和总生存期(２０.８个月对比１６.５个月)ꎬ显著提高左半ｍＣＲＣ患者的总生存期(２２.０个月对比１８.３个月)ꎬ得到了各大权威指南的推荐[１６－１９]ꎬ是结直肠癌治疗中疗效最为显著的靶向药物ꎬ能够有效缩瘤ꎮ然而在真实世界研究中ꎬ有效性指标却很难从医院的数据库中直接获得ꎬ通过划分８个大类对有效性进行界定ꎬ获得的有效性结果约６７％ꎮ但如果仅从缓解率结果来看ꎬ完全缓解加上部分缓解约为５％ꎬ这与临床试验中６０％左右的客观缓解率结果相差较大ꎬ说明进一步开展基于真实世界的疗效性研究具有一定的必要性ꎮ管理指南对于经济性方面的评价ꎬ建议选择成本－效果分析(ＣＥＡ)等一系列卫生技术评估的方法ꎮ但从真实世界数据出发ꎬ由于效果指标不易获得ꎬ构建经济学评价模型存在一定技术上的难度ꎮ考虑到有效性无统计学差异ꎬ本研究仅对费用进行了分析ꎬ可以为后续结直肠癌领域相关经济学评价的开展提供成本数据的参考ꎬ助力药品临床综合评价的开展ꎮ从可及性来看ꎬ本研究采用医疗卫生机构药品配备率进行评价ꎬ由于该类药品必须在有抗肿瘤药物使用经验的医师指导下使用ꎬ用药过程需密切监测患者状况ꎬ分母选择了山东省的肿瘤专科医院及有肿瘤科的医院数量ꎮ然而从可获得性方面来看ꎬ西妥昔单抗在二㊁三级医院与各地市的配备率均低于５０％ꎮ当前国际上对药品可获得率没有严格统一的标准ꎬ一般认为配备率<５０％为可获得率较低ꎬ５０％~８０％为可获得率较好ꎬ>８０％为可获得率很好ꎮ从创新性和适宜性的评价来看ꎬ缺乏量化的相关指标ꎬ评价较为主观ꎮ４㊀局限性本研究存在着一定的不足和局限性ꎮ由于当前的数据可获得性有限ꎬ本研究基于山东省两家医院的真实世界数据ꎬ回顾性分析西妥昔单抗在临床实际应用情况ꎬ由于头颈部鳞癌的适应证获批时间较短ꎬ真实世界使用西妥昔单抗治疗的头颈部鳞癌患者病例数非常少ꎬ所以未纳入头颈部鳞癌患者进行有效性㊁经济性评价ꎻ仅从综合医院获取应用贝伐珠单抗以及应用传统化疗方案治疗结直肠癌患者的病例作为对照组ꎬ本研究纳入的使用西妥昔单抗治疗的结直肠癌患者ꎬ均为基因检测结果ＲＡＳ野生型ꎬ使用贝伐单抗和传统化疗的患者大多数未进行基因检测ꎬ所以未对ＲＡＳ基因型这一变量进行分析ꎬ存在一定的选择偏倚ꎻ另外ꎬ部分指标存在着主观性强㊁无法量化的问题ꎮ因此有必要继续探索开展多维度综合评价ꎬ通过专家咨询等方法对各个方面的证据进行整合后的综合评价ꎬ进一步提升评价结果的科学性和可推广性ꎮ５㊀结论本研究通过开展基于真实世界数据的西妥昔单抗临床综合评价ꎬ从安全性㊁有效性㊁经济性㊁创新性㊁适宜性㊁可及性等多个维度对西妥昔单抗进行综合评价ꎬ作为治疗结直肠癌一线药物ꎬ西妥昔单抗在安全性㊁有效性㊁经济性㊁适宜性与贝伐珠单抗整体无显著性差异ꎬ仅皮疹发生率明显高于贝伐珠单抗ꎬ对于ＲＡＳ基因野生型患者疗效优势明显ꎻ作为治疗头颈部鳞癌药物ꎬ对复发和/或转移头颈部鳞癌提供了新的治疗选择ꎬ具有一定创新性ꎻ在山东地区的可获得性和可负担性相对较差ꎮ参考文献:[１]㊀国家卫生健康委办公厅.关于规范开展药品临床综合评价工作的通知[ＥＢ/ＯＬ].(２０２１－０７－２１)[２０２３－０７－２８].ｈｔｔｐ://ｗｗｗ.ｎｈｃ.ｇｏｖ.ｃｎ/ｙａｏｚｓ/ｓ２９０８/２０２１０７/５３２ｅ２０８００ａ４７４１５ｄ８４ａｄｆ３７９７ｂ０ｆ４８６９.ｓｈｔｍｌ.[２]国家药物和卫生技术综合评估中心关于发布心血管病㊁抗肿瘤㊁儿童药品临床综合评价技术指南的通知[ＥＢ/ＯＬ].(２０２２－０６－２９)[２０２３－０７－２８].ｈｔｔｐ://ｗｗｗ.０ｎｈｅｉ.ｃｎ/ｎｈｅｉ/ｚｎｆｂ/２０２２０６/ｃ０１ｄ８７ａ２９０６６４ｂ０１ｂｆ４２ａ９ｄａｄ７６９ｄ６９ｆ.ｓｈｔｍｌ.[３]ＳＵＮＧＨꎬＦＥＲＬＡＹＪꎬＳＩＥＧＥＬＲＬꎬｅｔａｌ.ＧｌｏｂａｌＣａｎｃｅｒＳｔａｔｉｓｔｉｃｓ２０２０:ＧＬＯＢＯＣＡＮＥｓｔｉｍａｔｅｓｏｆＩｎｃｉｄｅｎｃｅａｎｄＭｏｒｔａｌｉｔｙＷｏｒｌｄｗｉｄｅｆｏｒ３６Ｃａｎｃｅｒｓｉｎ１８５Ｃｏｕｎｔｒｉｅｓ[Ｊ].ＣＡＣａｎｃｅｒＪＣｌｉｎꎬ２０２１ꎬ７１(３):２０９－２４９.[４]陈万青ꎬ孙可欣ꎬ郑荣寿ꎬ等.２０１４年中国分地区恶性肿瘤发病和死亡分析[Ｊ].中国肿瘤ꎬ２０１８ꎬ２７(１):１－１４.[５]高嘉敏ꎬ冯群ꎬ许晓燕ꎬ等.结直肠癌抗代谢药物及其代谢靶点研究进展[Ｊ].中国新药与临床杂志ꎬ２０２０ꎬ３９(３):１３４－１４０.[６]覃肖潇ꎬ金春林ꎬ王美凤ꎬ等.含钆对比剂的临床综合评价[Ｊ].临床药物治疗杂志ꎬ２０２１ꎬ１９(９):３４－４０. [７]符雨嫣ꎬ金春林ꎬ孙辉ꎬ等.晚期肝癌一线系统治疗药品的临床综合评价[Ｊ].临床药物治疗杂志ꎬ２０２１ꎬ１９(１０):６６－７０.[８]程文迪ꎬ金春林ꎬ罗雅双ꎬ等.眼科抗血管内皮生长因子药品的临床综合评价[Ｊ].临床药物治疗杂志ꎬ２０２１ꎬ１９(１０):５２－５９.[９]ＧＵＯＹꎬＬＵＹꎬＨＡＮＧＱꎬｅｔａｌ.ＬＢＡ６－Ｆｉｒｓｔ－ｉｎｅｃｅｔｕｘｉｍａｂｐｌｕｓｃｉｓｐｌａｔｉｎａｎｄｆｌｕｏｒｏｕｒａｃｉｌｓｃｉｓｐｌａｔｉｎａｎｄｆｌｕｏｒｏｕｒａｃｉｌｉｎＣｈｉｎｅｓｅｐａｔｉｅｎｔｓｗｉｔｈｒｅｃｕｒｒｅｎｔａｎｄ/ｏｒｍｅｔａｓｔａｔｉｃｓｑｕａ￣ｍｏｕｓｃｅｌｌｃａｒｃｉｎｏｍａｏｆｔｈｅｈｅａｄａｎｄｎｅｃｋ:Ｔｈｅｒａｎｄｏｍ￣ｉｚｅｄꎬｐｈａｓｅＩｌｌＣＨＡＮＧＥ－２ｔｒｉａｌ[Ｃ].ＣＳＣＯꎬ２０１９. [１０]ＨＥＩＮＥＭＡＮＮＶꎬＶＯＮＷＥＩＫＥＲＳＴＨＡＬＬＦꎬＤＥＣＫＥＲＴꎬｅｔａｌ.ＦＯＬＦＩＲＩｐｌｕｓｃｅｔｕｘｉｍａｂｖｅｒｓｕｓＦＯＬＦＩＲＩｐｌｕｓｂｅ￣ｖａｃｉｚｕｍａｂａｓｆｉｒｓｔ－ｌｉｎｅｔｒｅａｔｍｅｎｔｆｏｒｐａｔｉｅｎｔｓｗｉｔｈｍｅｔａ￣ｓｔａｔｉｃｃｏｌｏｒｅｃｔａｌｃａｎｃｅｒ(ＦＩＲＥ－３):ａｒａｎｄｏｍｉｓｅｄꎬｏｐｅｎ－ｌａｂｅｌꎬｐｈａｓｅ３ｔｒｉａｌ[Ｊ].ＬａｎｃｅｔＯｎｃｏｌꎬ２０１４ꎬ１５(１０):１０６５－１０７５.[１１]ＶＡＮＣＵＴＳＥＭＥꎬＬＥＮＺＨＪꎬＫＯＨＮＥＣＨꎬｅｔａｌ.Ｆｌｕｏｒｏｕ￣ｒａｃｉｌꎬｌｅｕｃｏｖｏｒｉｎꎬａｎｄｉｒｉｎｏｔｅｃａｎｐｌｕｓｃｅｔｕｘｉｍａｂｔｒｅａｔｍｅｎｔａｎｄＲＡＳｍｕｔａｔｉｏｎｓｉｎｃｏｌｏｒｅｃｔａｌｃａｎｃｅｒ[Ｊ].ＪＣｌｉｎＯｎｃｏｌꎬ２０１５ꎬ３３(７):６９２－７００.[１２]ＢＯＫＥＭＥＹＥＲＣꎬＢＯＮＤＡＲＥＮＫＯＩꎬＭＡＫＨＳＯＮＡꎬｅｔａｌ.Ｆｌｕｏｒｏｕｒａｃｉｌꎬｌｅｕｃｏｖｏｒｉｎꎬａｎｄｏｘａｌｉｐｌａｔｉｎｗｉｔｈａｎｄｗｉｔｈｏｕｔｃｅｔｕｘｉｍａｂｉｎｔｈｅｆｉｒｓｔ－ｌｉｎｅｔｒｅａｔｍｅｎｔｏｆｍｅｔａｓｔａｔｉｃｃｏｌｏｒｅｃｔａｌｃａｎｃｅｒ[Ｊ].ＪＣｌｉｎＯｎｃｏｌꎬ２００９ꎬ２７(５):６６３－６７１.[１３]ＱＩＮＳꎬＬＩＪꎬＷＡＮＧＬꎬｅｔａｌ.ＥｆｆｉｃａｃｙａｎｄＴｏｌｅｒａｂｉｌｉｔｙｏｆＦｉｒｓｔ－ＬｉｎｅＣｅｔｕｘｉｍａｂＰｌｕｓＬｅｕｃｏｖｏｒｉｎꎬＦｌｕｏｒｏｕｒａｃｉｌꎬａｎｄＯｘａｌｉｐｌａｔｉｎ(ＦＯＬＦＯＸ－４)ＶｅｒｓｕｓＦＯＬＦＯＸ－４ｉｎＰａｔｉｅｎｔｓＷｉｔｈＲＡＳＷｉｌｄ－ＴｙｐｅＭｅｔａｓｔａｔｉｃＣｏｌｏｒｅｃｔａｌＣａｎｃｅｒ:ＴｈｅＯｐｅｎ－ＬａｂｅｌꎬＲａｎｄｏｍｉｚｅｄꎬＰｈａｓｅＩＩＩＴＡＩＬＯＲＴｒｉａｌ[Ｊ].ＪＣｌｉｎＯｎｃｏｌꎬ２０１８ꎬ３６(３０):３０３１－３０３９.[１４]ＶＥＲＭＯＲＫＥＮＪＢꎬＭＥＳＩＡＲꎬＲＩＶＥＲＡＦꎬｅｔａｌ.Ｐｌａｔｉｎｕｍ－ｂａｓｅｄｃｈｅｍｏｔｈｅｒａｐｙｐｌｕｓｃｅｔｕｘｉｍａｂｉｎｈｅａｄａｎｄｎｅｃｋｃａｎｃｅｒ[Ｊ].ＮＥｎｇｌＪＭｅｄꎬ２００８ꎬ３５９(１１):１１１６－１１２７. [１５]任炳楠ꎬ赵越ꎬ薛朝军ꎬ等.治疗转移性结直肠癌的抗血管生成单克隆抗体的药品遴选量化评估[Ｊ].中国新药与临床杂志ꎬ２０２２ꎬ４１(６):３６７－３７３.[１６]中国医师协会外科医师分会ꎬ中华医学会外科分会胃肠外科学组ꎬ中华医学会外科分会结直肠外科学组ꎬ等.中国结直肠癌肝转移诊断和综合治疗指南(Ｖ２０２０)[Ｊ].中华结直肠疾病电子杂志ꎬ２０２１ꎬ１０(１):２－１５.[１７]国家卫生健康委员会医政医管局ꎬ中华医学会肿瘤学分会.中国结直肠癌诊疗规范(２０２０年版)[Ｊ].中国实用外科杂志ꎬ２０２０ꎬ４０(６):６０１－６２５.[１８]陈功ꎬ王屹.２０１７版欧洲肿瘤学会直肠癌指南解读[Ｊ].中华胃肠外科杂志ꎬ２０１７ꎬ２０(１１):１２３６－１２４２.[１９]龙飞ꎬ胡桂ꎬ马敏ꎬ等.２０２１.Ｖ１版ＮＣＣＮ临床实践指南:结肠癌/直肠癌更新解读(外科部分)[Ｊ].临床外科杂志ꎬ２０２１ꎬ２９(５):４０１－４０４.(收稿日期:２０２４－０１－０９)(上接第３９０页)[３８]ＹＯＵＹＰ.Ｅｐｉｇａｌｌｏｃａｔｅｃｈｉｎｇａｌｌａｔｅｅｘｔｅｎｄｓｔｈｅｔｈｅｒａｐｅｕｔｉｃｗｉｎｄｏｗｏｆｒｅｃｏｍｂｉｎａｎｔｔｉｓｓｕｅｐｌａｓｍｉｎｏｇｅｎａｃｔｉｖａｔｏｒｔｒｅａｔ￣ｍｅｎｔｉｎｉｓｃｈｅｍｉｃｒａｔｓ[Ｊ].ＪＳｔｒｏｋｅＣｅｒｅｂｒｏｖａｓｃＤｉｓꎬ２０１６ꎬ２５(４):９９０－９９７.[３９]ＺＵＯＷꎬＹＡＮＦꎬＺＨＡＮＧＢꎬｅｔａｌ.ＳａｌｉｄｒｏｓｉｄｅｉｍｐｒｏｖｅｓｂｒａｉｎｉｓｃｈｅｍｉｃｉｎｊｕｒｙｂｙａｃｔｉｖａｔｉｎｇＰＩ３Ｋ/ＡｋｔｐａｔｈｗａｙａｎｄｒｅｄｕｃｅｓｃｏｍｐｌｉｃａｔｉｏｎｓｉｎｄｕｃｅｄｂｙｄｅｌａｙｅｄｔＰＡｔｒｅａｔｍｅｎｔ[Ｊ].ＥｕｒＪＰｈａｒｍａｃｏｌꎬ２０１８(８３０):１２８－１３８.[４０]ＪＥＡＮＬＥＢＬＡＮＣＮꎬＭＥＮＥＴＲꎬＰＩＣＡＲＤＫꎬｅｔａｌ.ＣａｎｏｎｉｃａｌＷｎｔｐａｔｈｗａｙｍａｉｎｔａｉｎｓｂｌｏｏｄ－ｂｒａｉｎｂａｒｒｉｅｒｉｎ￣ｔｅｇｒｉｔｙｕｐｏｎｉｓｃｈｅｍｉｃｓｔｒｏｋｅａｎｄｉｔｓａｃｔｉｖａｔｉｏｎａｍｅｌｉｏｒａｔｅｓｔｉｓｓｕｅｐｌａｓｍｉｎｏｇｅｎａｃｔｉｖａｔｏｒｔｈｅｒａｐｙ[Ｊ].ＭｏｌＮｅｕｒｏｂｉｏｌꎬ２０１９ꎬ５６(９):６５２１－６５３８.[４１]ＷＡＮＧＷꎬＬＩＭꎬＷＡＮＧＹꎬｅｔａｌ.ＧＳＫ－３βｉｎｈｉｂｉｔｏｒＴＷＳ１１９ａｔｔｅｎｕａｔｅｓｒｔＰＡ－ｉｎｄｕｃｅｄｈｅｍｏｒｒｈａｇｉｃｔｒａｎｓｆｏｒ￣ｍａｔｉｏｎａｎｄａｃｔｉｖａｔｅｓｔｈｅＷｎｔ/β－ｃａｔｅｎｉｎｓｉｇｎａｌｉｎｇｐａｔｈｗａｙａｆｔｅｒａｃｕｔｅｉｓｃｈｅｍｉｃｓｔｒｏｋｅｉｎｒａｔｓ[Ｊ].ＭｏｌＮｅｕｒｏ￣ｂｉｏｌꎬ２０１６ꎬ５３(１０):７０２８－７０３６.[４２]ＷＡＮＧＴꎬＤＵＡＮＹＭꎬＦＵＱꎬｅｔａｌ.ＩＭ－１２ａｃｔｉｖａｔｅｓｔｈｅＷｎｔ－β－ｃａｔｅｎｉｎｓｉｇｎａｌｉｎｇｐａｔｈｗａｙａｎｄａｔｔｅｎｕａｔｅｓｒｔＰＡ－ｉｎｄｕｃｅｄｈｅｍｏｒｒｈａｇｉｃｔｒａｎｓｆｏｒｍａｔｉｏｎｉｎｒａｔｓａｆｔｅｒａｃｕｔｅｉｓｃｈｅｍｉｃｓｔｒｏｋｅ[Ｊ].ＢｉｏｃｈｅｍＣｅｌｌＢｉｏｌꎬ２０１９ꎬ９７(６):７０２－７０８.[４３]ＬＩＵＣꎬＳＵＮＳꎬＸＩＥＪꎬｅｔａｌ.ＧＬＰ－１ＲａｇｏｎｉｓｔＥｘｅｎｄｉｎ－４ｐｒｏ￣ｔｅｃｔｓａｇａｉｎｓｔｈｅｍｏｒｒｈａｇｉｃｔｒａｎｓｆｏｒｍａｔｉｏｎｉｎｄｕｃｅｄｂｙｒｔＰＡａｆｔｅｒｉｓｃｈｅｍｉｃｓｔｒｏｋｅｖｉａｔｈｅＷｎｔ/β－Ｃａｔｅｎｉｎｓｉｇｎａｌｉｎｇｐａｔｈ￣ｗａｙ[Ｊ].ＭｏｌＮｅｕｒｏｂｉｏｌꎬ２０２２ꎬ５９(６):３６４９－３６６４.[４４]ＲＥＮＷꎬＨＵＡＮＧＣꎬＣＨＵＨꎬｅｔａｌ.Ｐｅｐｔｉｄｅ５ａｔｔｅｎｕａｔｅｓｒｔＰＡｒｅｌａｔｅｄｂｒａｉｎｍｉｃｒｏｖａｓｃｕｌａｒｅｎｄｏｔｈｅｌｉａｌｃｅｌｌｓｒｅｐｅｒｆｕ￣ｓｉｏｎｉｎｊｕｒｙｖｉａｔｈｅＷｎｔ/β－ｃａｔｅｎｉｎｓｉｇｎａｌｌｉｎｇｐａｔｈｗａｙ[Ｊ].ＣｕｒｒＮｅｕｒｏｖａｓｃＲｅｓꎬ２０２１ꎬ１８(２):２１９－２２６.[４５]ＺＨＡＮＧＬꎬＸＵＳꎬＷＵＸꎬｅｔａｌ.Ｃｏｍｂｉｎｅｄｔｒｅａｔｍｅｎｔｗｉｔｈ２－(２－ｂｅｎｚｏｆｕ－ｒａｎｙｌ)－２－ｉｍｉｄａｚｏｌｉｎｅａｎｄｒｅｃｏｍｂｉｎａｎｔｔｉｓ￣ｓｕｅｐｌａｓｍｉｎｏｇｅｎａｃｔｉｖａｔｏｒｐｒｏｔｅｃｔｓｂｌｏｏｄ－ｂｒａｉｎｂａｒｒｉｅｒｉｎ￣ｔｅｇｒｉｔｙｉｎａｒａｔｍｏｄｅｌｏｆｅｍｂｏｌｉｃｍｉｄｄｌｅｃｅｒｅｂｒａｌａｒｔｅｒｙｏｃ￣ｃｌｕｓｉｏｎ[Ｊ].ＦｒｏｎｔＰｈａｒｍａｃｏｌꎬ２０２０(１１):８０１.[４６]ＯＲＳＥＴＣꎬＡＲＫＥＬＩＵＳＫꎬＡＮＦＲＡＹＡꎬｅｔａｌ.ＣｏｍｂｉｎａｔｉｏｎｔｒｅａｔｍｅｎｔｗｉｔｈＵ０１２６ａｎｄｒｔ－ＰＡｐｒｅｖｅｎｔｓａｄｖｅｒｓｅｅｆｆｅｃｔｓｏｆｔｈｅｄｅｌａｙｅｄｒｔ－ＰＡｔｒｅａｔｍｅｎｔａｆｔｅｒａｃｕｔｅｉｓｃｈｅｍｉｃｓｔｒｏｋｅ[Ｊ].ＳｃｉＲｅｐꎬ２０２１ꎬ１１(１):１１９９３.[４７]ＫＮＥＣＨＴＴꎬＳＴＯＲＹＪꎬＬＩＵＪꎬｅｔａｌ.Ａｄｊｕｎｃｔｉｖｅｔｈｅｒａｐｙａｐ￣ｐｒｏａｃｈｅｓｆｏｒｉｓｃｈｅｍｉｃｓｔｒｏｋｅ:ｉｎｎｏｖａｔｉｏｎｓｔｏｅｘｐａｎｄｔｉｍｅｗｉｎｄｏｗｏｆｔｒｅａｔｍｅｎｔ[Ｊ].ＩｎｔＪＭｏｌＳｃｉꎬ２０１７ꎬ１８(１２):２７５６.[４８]ＹＩＮＢꎬＬＩＤＤꎬＸＵＳＹꎬｅｔａｌ.Ｓｉｍｖａｓｔａｔｉｎｐｒｅｔｒｅａｔｍｅｎｔａ￣ｍｅｌｉｏｒａｔｅｓｔ－ＰＡ－ｉｎｄｕｃｅｄｈｅｍｏｒｒｈａｇｅｔｒａｎｓｆｏｒｍａｔｉｏｎａｎｄＭＭＰ－９/ＴＩＭＰ－１ｉｍｂａｌａｎｃｅｉｎｔｈｒｏｍｂｏｅｍｂｏｌｉｃｃｅｒｅｂｒａｌｉｓｃｈｅｍｉｃｒａｔｓ[Ｊ].ＮｅｕｒｏｐｓｙｃｈｉａｔｒＤｉｓＴｒｅａｔꎬ２０１９(１５):１９９３－２００２.[４９]ＬＩＵＤＬꎬＨＯＮＧＺꎬＬＩＪＹꎬｅｔａｌ.ＰｈｔｈａｌｉｄｅｄｅｒｉｖａｔｉｖｅＣＤ２１ａｔｔｅｎｕａｔｅｓｔｉｓｓｕｅｐｌａｓｍｉｎｏｇｅｎａｃｔｉｖａｔｏｒ－ｉｎｄｕｃｅｄｈｅｍｏｒｒｈａｇｉｃｔｒａｎｓｆｏｒｍａｔｉｏｎｉｎｉｓｃｈｅｍｉｃｓｔｒｏｋｅｂｙｅｎｈａｎｃｉｎｇｍａｃｒｏｐｈａｇｅｓｃａｖｅｎｇｅｒｒｅｃｅｐｔｏｒ１－ｍｅｄｉａｔｅｄＤＡＭＰ(ｐｅｒｏｘｉｒｅｄｏｘｉｎ１)ｃｌｅａｒａｎｃｅ[Ｊ].ＪＮｅｕｒｏｉｎｆｌａｍｍａ￣ｔｉｏｎꎬ２０２１ꎬ１８(１):１４３.[５０]ＬＩＹꎬＺＨＵＺＹꎬＬＵＢＷꎬｅｔａｌ.Ｒｏｓｉｇｌｉｔａｚｏｎｅａｍｅｌｉｏｒａｔｅｓｔｉｓｓｕｅｐｌａｓｍｉｎｏｇｅｎａｃｔｉｖａｔｏｒ－ｉｎｄｕｃｅｄｂｒａｉｎｈｅｍｏｒｒｈａｇｅａｆｔｅｒｓｔｒｏｋｅ[Ｊ].ＣＮＳＮｅｕｒｏｓｃｉＴｈｅｒꎬ２０１９ꎬ２５(１２):１３４３－１３５２. [５１]ＩＳＭＡＥＬＳꎬＮＡＳＯＯＨＩＳꎬＹＯＯＡꎬｅｔａｌ.ＶｅｒａｐａｍｉｌａｓａｎａｄｊｕｎｃｔｔｈｅｒａｐｙｔｏｒｅｄｕｃｅｔＰＡｔｏｘｉｃｉｔｙｉｎｈｙｐｅｒｇｌｙｃｅｍｉｃｓｔｒｏｋｅ:ｉｍｐｌｉｃａｔｉｏｎｏｆＴＸＮＩＰ/ＮＬＲＰ３ｉｎｆｌａｍｍａｓｏｍｅ[Ｊ].ＭｏｌＮｅｕｒｏｂｉｏｌꎬ２０２１ꎬ５８(８):３７９２－３８０４.[５２]ＬＵＤꎬＬＩＵＹꎬＭＡＩＨꎬｅｔａｌ.Ｒｏｓｕｖａｓｔａｔｉｎｒｅｄｕｃｅｓｎｅｕｒｏｉｎ￣ｆｌａｍｍａｔｉｏｎｉｎｔｈｅｈｅｍｏｒｒｈａｇｉｃｔｒａｎｓｆｏｒｍａｔｉｏｎａｆｔｅｒｒｔ－ＰＡｔｒｅａｔｍｅｎｔｉｎａｍｏｕｓｅｍｏｄｅｌｏｆｅｘｐｅｒｉｍｅｎｔａｌｓｔｒｏｋｅ[Ｊ].ＦｒｏｎｔＣｅｌｌＮｅｕｒｏｓｃｉꎬ２０１８(１２):２２５.[５３]ＣＨＥＮＨꎬＧＵＡＮＢꎬＷＡＮＧＢꎬｅｔａｌ.Ｇｌｙｃｙｒｒｈｉｚｉｎｐｒｅｖｅｎｔｓｈｅｍｏｒｒｈａｇｉｃｔｒａｎｓｆｏｒｍａｔｉｏｎａｎｄｉｍｐｒｏｖｅｓｎｅｕｒｏｌｏｇｉｃａｌｏｕｔ￣ｃｏｍｅｉｎｉｓｃｈｅｍｉｃｓｔｒｏｋｅｗｉｔｈｄｅｌａｙｅｄｔｈｒｏｍｂｏｌｙｓｉｓｔｈｒｏｕｇｈｔａｒｇｅｔｉｎｇｔｅｒｏｘｙｎｉｔｒｉｔｅ－ｍｅｄｉａｔｅｄＨＭＧＢ１ｓｉｇｎａｌｉｎｇ[Ｊ].ＴｒａｎｓｌＳｔｒｏｋｅＲｅｓꎬ２０２０ꎬ１１(５):９６７－９８２.(收稿日期:２０２３－０４－２６)。
奥希替尼结构式 -回复
奥希替尼结构式-回复奥希替尼（Axitinib）是一种口服靶向治疗肾细胞癌（Renal Cell Carcinoma，RCC）的药物。
它属于酪氨酸激酶抑制剂，通过抑制肿瘤细胞中的血管内皮生长因子受体（Vascular Endothelial Growth Factor Receptor，VEGFR）来阻止肿瘤生长和进展。
奥希替尼的结构式如下：[图片插入奥希替尼的结构式]在本文中，我们将一步一步回答关于奥希替尼结构式的相关问题，并探讨它的作用机制以及在肾细胞癌治疗中的应用。
第一步：理解奥希替尼的结构奥希替尼的结构式中包含多个环和侧链，每个原子都有特定的位置和键。
通过仔细观察结构式，我们可以看到氮原子、氧原子和氢原子的排列方式。
这些原子的位置和键的连接方式决定了奥希替尼的化学性质和药理学特性。
第二步：认识酪氨酸激酶（Tyrosine Kinase）抑制剂酪氨酸激酶是一类蛋白酶，参与调控细胞的生长、分化和凋亡。
在肾细胞癌中，血管内皮生长因子（VEGF）的过度表达会导致血管生成和肿瘤细胞的增殖，从而促进肿瘤的生长和转移。
酪氨酸激酶抑制剂通过抑制VEGF 受体（VEGFR）的激活，阻断信号传导通路，抑制血管生成和肿瘤细胞增殖，从而抑制肿瘤生长并延长患者的生存期。
第三步：奥希替尼的作用机制奥希替尼是一种选择性VEGFR抑制剂，它主要抑制VEGFR-1、VEGFR-2和VEGFR-3的激活。
VEGFR-1和VEGFR-2被认为是VEGF信号传导的关键受体，其过度激活与肾细胞癌的发展有关。
奥希替尼的结构与VEGFR 结构相似，可以与VEGFR结合并竞争性抑制VEGF的结合，从而阻断VEGF 信号传导通路。
第四步：奥希替尼在肾细胞癌治疗中的应用奥希替尼已被美国食品药品监督管理局（FDA）批准用于晚期或转移性肾细胞癌的治疗。
临床试验表明，奥希替尼与传统的免疫疗法相比，能够延长患者的生存期。
它被广泛应用于一线和二线治疗中，通常与其他化疗药物或免疫治疗方案联合使用。
AZD-9291_突变型EGFR抑制剂。_1421373-65-0_Apexbio
AZD-9291 是一种不可逆的突变型 EGFR 抑制剂，作用于 EGFR（外显子 19 缺失）、EGFR （L858R/T790M）和 EGFR（野生型），IC50 值分别为 17 nM、15 nM 和 480 nM。 EGFR 突变型会引起药物的耐受性，因而研发了一种针对突变型 EGFR 的选择性抑制剂
动物实验: 动物模型 剂量 应用
EGFRm+和 EGFRm+/ T790M 转基因小鼠
5 mg/kg
在 EGFRm+（PC9）和 EGFRm+/ T790M（H1975）肿瘤模型中， AZD9291 以 5 mg/kg 的剂量每天一次口服给药，14 天后引起显著 的肿瘤消退，分别获得了 178%和 119%的生长抑制。而且，5 mg/kg 的 AZD9291 可引起 EGFRm+和 EGFRm+/ T790M 转基因小鼠肺肿瘤 的显著收缩。肿瘤生长抑制与 EGFR 磷酸化的显著抑制以及关键 的下游信号通路（比如 AKT 和 ERK）相关。在 PC9 和 H1975 异种 移植肿瘤中，AZD9291 的慢性长期治疗可引起完全和持续性的效 应，在连续 40 天给药后没有可见的肿瘤，并一直维持 100 天以 上。而且，临床前数据显示，对于已获得 HER-2 扩增机制抗性的 肿瘤，AZD9291 也具有效果，因而其在 TKI 耐药患者中也可能起
参考文献: [1] Darren A. E. Cross, Susan E Ashton, Serban Ghiorghiu, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discovery. 2014, June.
2013年6月20日发布最新影响因子IF_完整版
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1.373378 929ASTROPHYS J0004-637X191940 6.733 5.945 2.0473075 1764CIRC-CARDIOVASC GENE1942-325X1641 6.728 6.398 1.17182 6921PHYS REV X2160-3308414 6.711 6.737 2.22571 6158MOL ONCOL1574-78911193 6.701 6.3790.91760 1768CIRC-HEART FAIL1941-32892007 6.684 6.67 1.41993 1309BMC MED1741-70152691 6.679 6.413 1.275109 1820CLIN GASTROENTEROL H1542-35658295 6.648 6.108 1.458179 6561ONCOTARGET1949-25531450 6.636 6.636 1.316114 2177CURR OPIN COLLOID IN1359-02944670 6.6297.0360.88443 2862EXPERT REV MOL MED1462-39941734 6.6230.78919 1417BRIT J PSYCHIAT0007-125021472 6.6067.112 1.872117 1019B AM METEOROL SOC0003-000711821 6.5917.704 2.48778 5280J PHYS CHEM LETT1948-71858575 6.585 6.651 1.301632 6902PHYS LIFE REV1571-0645659 6.583 6.699.45511 6990PLANT J0960-741232497 6.5827.113 1.5333456997PLANT PHYSIOL0032-088962407 6.5557.084 1.313469 5605JACC-CARDIOVASC INTE1936-87983378 6.552 6.834 1.603126 2396DRUG DISCOV TODAY1359-64468855 6.551 6.89 1.177158 271ADV MICROB PHYSIOL0065-29111006 6.545 6.267 1.25 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6.986 1.097370 636ANN SURG0003-493236761 6.3298.264 1.15301 6973PLANT BIOTECHNOL J1467-76443136 6.279 5.813 1.04101 6139MOL ECOL0962-108330411 6.275 6.792 1.369445 2110CRIT REV TOXICOL1040-84442955 6.253 5.9720.94335 6339NEUROIMAGE1053-811961770 6.2527.063 1.2911222 2595ENVIRON INT0160-41209059 6.248 6.1220.935199 5339J PSYCHIATR NEUROSCI1180-48822253 6.242 6.473 1.64734 6226NANOSCALE2040-33647835 6.233 6.262 1.1671015 7886STUD MYCOL0166-06161237 6.231 6.813 4.1676 6869PHILOS T R SOC B0962-843626581 6.237.298 3.522289 2310DEVELOPMENT0950-199151191 6.208 6.888 1.258434 7648SEMIN CELL DEV BIOL1084-95215613 6.202 6.51 1.034116 3764INT J CANCER0020-713644529 6.198 5.474 1.39738 4915J INVEST DERMATOL0022-202X23976 6.193 6.065 1.898264 471AM J TRANSPLANT1600-613516088 6.192 6.014 1.506348 6318NEURO-ONCOLOGY1522-85173845 6.18 5.9470.694157 231ADV COLLOID INTERFAC0001-86867115 6.1698.01 1.3250 6320NEUROBIOL AGING0197-458015479 6.166 6.098 1.583537 5604JACC-CARDIOVASC IMAG1936-878X2977 6.164 6.703 1.717113 2080CORTEX0010-94525265 6.161 5.042 2.745106 7864STROKE0039-249952524 6.158 6.831 1.086567 1640CHEM BIOL1074-55219695 6.157 6.097 1.486144 6621ORG LETT1523-706073440 6.142 5.563 1.5721608 4378J BONE MINER RES0884-043122111 6.128 6.227 1.101257 6165MOL PLANT1674-20522346 6.126 5.77 1.585118 2094CRIT CARE MED0090-349332733 6.124 6.401 2.614363 2371DIVERS DISTRIB1366-95164336 6.122 5.7430.935107 1863CLIN PHARMACOKINET0312-******** 6.109 5.4860.98154 8313WHO TECH REP SER0512-******** 6.1 3.2560.35714 8039THROMB HAEMOSTASIS0340-624517392 6.094 4.782 1.3462465510J THROMB HAEMOST1538-793314645 6.081 6.176 1.17265 5876MATER TODAY1369-70213769 6.0718.677 1.97744 1578CELL DEATH DIS2041-48891481 6.044 6.0440.565191 4548J COSMOL ASTROPART P1475-751613656 6.036 5.295 2.387555 1523CANCER TREAT REV0305-73724233 6.024 6.246 1.458107 7131PROG NUCL MAG RES SP0079-65651993 6.022 6.065 1.38918 1285BLOOD REV0268-960X17706 6.6620.76939 7877STRUCTURE0969-212612441 5.994 6.081 1.466191 2519EMERG INFECT DIS1080-604021567 5.993 6.312 1.689244 322AGEING RES REV1568-16371965 5.953 6.549 1.43941 7706SIAM REV0036-14455051 5.9528.4140.40922 1763CIRC-ARRHYTHMIA ELEC1941-31492173 5.947 6.434 1.175143 2108CRIT REV SOLID STATE1040-8436744 5.9477.368110 1543CARDIOVASC RES0008-636320689 5.94 6.113 1.689222 3241HAEMATOL-HEMATOL J0390-607811392 5.935 6.002 1.454251 7654SEMIN IMMUNOL1044-53233190 5.9267.250.89146 6031METHODS ECOL EVOL2041-210X822 5.92460.854123 203ADDICT BIOL1355-62151977 5.914 5.322 1.01193 1081BASIC RES CARDIOL0300-84283292 5.904 5.362 1.16772 6390NEUROTHERAPEUTICS1933-72131923 5.904 5.720.90563 381ALLERGY0105-453812173 5.883 5.983 1.58193 4422J CELL SCI0021-953340261 5.877 6.375 1.032535 1391BREAST CANCER RES1465-542X7547 5.872 6.2640.82172 1528CARBON0008-622332742 5.868 6.35 1.197674 2915FISH FISH1467-29601846 5.8557.326 1.53826 1699CHEST0012-369244596 5.854 6.42 3.394307 4871J INFECT DIS0022-189942783 5.848 5.914 1.556493 2189CURR OPIN LIPIDOL0957-96723620 5.839 5.7380.92264 6966PIGM CELL MELANOMA R1755-14713385 5.839 5.434 1.39768 1685CHEM-EUR J0947-653960788 5.831 5.623 1.2411916 717APPL CATAL B-ENVIRON0926-337323011 5.825 6.0310.965480 4486J CLIN PSYCHIAT0160-668917639 5.812 5.6390.726157 1765CIRC-CARDIOVASC IMAG1941-96511650 5.795 6.579 1.17984 5924MAYO CLIN PROC0025-61969444 5.79 5.638 1.44109 4413J CATAL0021-951734516 5.787 6.249 1.025284 5164J NUCL MED0161-550521262 5.774 6.4020.934243 2597ENVIRON MICROBIOL1462-291213228 5.756 5.943 1.455242 2626EPIDEMIOLOGY1044-39838979 5.738 6.241 2.12588 8328WIRES COMPUT MOL SCI1759-0876570 5.738 5.738 3.51856 2539ENDOSCOPY0013-726X8401 5.735 5.355 1.514144 4048INT REV IMMUNOL0883-******* 5.733 4.140.44829 324AGING CELL1474-97184134 5.705 6.415 1.485130 2885FASEB J0892-663839540 5.704 6.222 1.13462 1895COCHRANE DB SYST REV1469-493X34230 5.703 6.5120.728977 5027J MED GENET0022-259311563 5.703 5.793 1.353116 5687LAB CHIP1473-019716485 5.697 6.136 1.256617 510ANAL CHEM0003-270096794 5.695 5.7690.9481479 6697P ROY SOC B-BIOL SCI0962-845237539 5.683 5.832 1.224624 8330WIRES NANOMED NANOBI1939-5116983 5.681 6.34 1.08547 1767CIRC-CARDIOVASC QUAL1941-77051551 5.658 5.647 1.43100 7369RETROVIROLOGY1742-46903084 5.657 4.857 1.505107 6713PAIN0304-395929370 5.644 6.125 1.264269 3917INT J NEUROPSYCHOPH1461-14574003 5.641 5.0920.805123 1530CARCINOGENESIS0143-333421223 5.635 5.5570.9553106383NEUROSCIENTIST1073-85843259 5.633 6.417 1.35645 7327RENEW SUST ENERG REV1364-032110347 5.627 6.5770.803584 6321NEUROBIOL DIS0969-996111288 5.624 5.482 1.493296 5925MBIO2150-75111260 5.621 5.621 1.536151 4817J HIGH ENERGY PHYS1126-670852898 5.618 4.712 2.6581861 1589CELL MOL LIFE SCI1420-682X17974 5.615 6.359 1.072290 5022J MED CHEM0022-262359227 5.614 5.383 1.225890 1362BRAIN BEHAV IMMUN0889-15916137 5.612 5.698 1.082147 6124MOL CANCER THER1535-716314654 5.599 5.72 1.201259 1873CLIN REV ALLERG IMMU1080-05491685 5.59 3.955 1.30662 7194PSYCHOL MED0033-291716680 5.587 6.1480.913230 2098CRIT REV 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ELECTRON0278-004617404 5.165 5.0780.943470 528ANESTHESIOLOGY0003-302222547 5.163 5.302 1.959219 5065J MOL CELL CARDIOL0022-282811674 5.148 5.034 1.478232 7200PSYCHONEUROENDOCRINO0306-45309603 5.137 5.926 1.091198 6978PLANT CELL ENVIRON0140-779114009 5.135 5.861 1.639158 6122MOL CANCER1476-45984995 5.134 5.0970.3686 6849PHARMACOGENOMICS J1470-269X2084 5.134 4.455 1.12365 2444ECOGRAPHY0906-******** 5.124 5.7910.925120 2179CURR OPIN DRUG DISC1367-67331825 5.121 4.1080 3657INFLAMM BOWEL DIS1078-09988279 5.119 5.233 1.161261 6801PEDIATRICS0031-400559035 5.119 5.930.951687 2702EUR J EPIDEMIOL0393-******** 5.118 4.1160.49489 2729EUR J NUCL MED MOL I1619-707010881 5.114 4.821 1.202198 4805J HEART LUNG TRANSPL1053-24987139 5.112 3.6270.975159 5104J NATL COMPR CANC NE1540-14051890 5.1120.522115 7318REMOTE SENS ENVIRON0034-425724105 5.103 6.1440.987388 7724SLEEP0161-810514444 5.1 6.175 1.068162 2099CRIT REV BIOTECHNOL0738-******** 5.095 5.9660.95221 604ANN MED0785-38903665 5.094 4.640.76397 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DEV1991-959X626 5.03 4.50.84691 6186MRS BULL0883-******** 5.024 5.590.569116 3269HEART1355-603713857 5.014 4.769 1.667243 48ACS APPL MATER INTER1944-82448635 5.008 5.040.683953 2491ELECTROANAL CHEM0070-977837757.50.254 216ADV APPL MICROBIOL0065-21641233 4.974 4.7840.33321 4045INT REV CEL MOL BIO1937-6448825 4.973 4.9440.40849 2713EUR J IMMUNOL0014-298020974 4.97 4.7680.739322 663ANNU REV ENV RESOUR1543-59381402 4.9687.25018 923ASTRON J0004-625634668 4.965 4.571 1.162334 6154MOL MICROBIOL0950-382X37172 4.961 5.099 1.123359 2351DIS MODEL MECH1754-84031212 4.959 5.0090.98988 1407BRIT J HAEMATOL0007-104820668 4.942 4.7260.891266 4497J COMB CHEM1520-47662925 4.933 3.1020 5789MACROMOL RAPID COMM1022-133612103 4.929 4.6180.916261 5129J NEUROL NEUROSUR PS0022-305023923 4.924 5.144 1.69187 2628EPIGENETICS-US1559-22942289 4.92 4.8810.773150 4050INT REV PHYS CHEM0144-235X1524 4.92 5.595 2.23113 1119BEST PRACT RES CL EN1521-690X2576 4.912 5.1810.25866 1091BBA-MOL BASIS DIS0925-44396277 4.91 4.932 1.248202 5451J STAT SOFTW1548-76602629 4.91 5.9070.75377 5356J R SOC INTERFACE1742-56895016 4.907 5.1650.806320 4206J AM ACAD DERMATOL0190-962219760 4.906 4.5150.896280 1518CANCER PREV RES1940-62073114 4.891 5.126 1.401142 2187CURR OPIN INFECT DIS0951-******** 4.87 4.610.83987 2846EXPERT OPIN DRUG DEL1742-52472829 4.869 5.1330.495103 469AM J SURG PATHOL0147-518516422 4.868 4.8570.798223 7021PLOS COMPUT BIOL1553-735811758 4.867 5.9390.824507 6837PFLUG ARCH EUR J PHY0031-67689307 4.866 3.9280.853129 2810EVOLUTION0014-382030585 4.864 5.4020.939313 4347J BIOGEOGR0305-027010682 4.863 4.979 1.399183 3042FUNCT ECOL0269-84639681 4.861 5.3930.882153 2231CURR TOP MICROBIOL0070-217X4958 4.86 4.744 5.05319 1875CLIN SCI0143-52218069 4.859 4.843 1.2110 174ACTA PSYCHIAT SCAND0001-690X11048 4.857 4.625198 386ALTERN MED REV1089-51591288 4.857 5.0340.56 250ADV GENET0065-26601198 4.85 4.102010 4253J ANIM ECOL0021-879012354 4.841 5.1660.881134。
肺癌靶向治疗最新药物
肺癌靶向治疗最新药物来自吉林长春的林先生化名从2021年年底开始咳嗽，两月来一直没得到缓解，经支气管活检，结果显示为肺腺癌。
因为肿瘤位置靠近主动脉无法手术，只能化疗。
经过两个疗程的化疗，林先生实在无法耐受化疗的副作用。
在主治医生的建议下，林先生决定做基因检测，看是否可以口服靶向药物。
幸运的是，林先生的EGFR基因有突变，可以口服“易瑞沙”，效果明显。
2021年3月，林先生的病情出现了变化，考虑易瑞沙出现耐药性。
在主治医生的推荐下，林先生再次做了基因检测，看EGFR基因20号外显子第790位点是否有突变。
如果有突变，林先生可以考虑服用AZD9291。
基因检测结果显示林先生EGFR基因20号外显子第790位点有突变，可以服用AZD9291。
阿斯利康生产的AZD9291商品名TAGRISSO，奥希替尼在2021年11月13日得了美国FDA的批准，目前还没有在中国上市。
主要用于治疗曾经使用过表皮生长因子EGFR酪氨酸激酶抑制剂后，出现疾病进展，且耐药原因为T790M突变EGFR基因20号外显子第790位点的突变阳性的非小细胞肺癌NSCLC患者。
也就是说适用人群为：肺癌患者服用易瑞沙，特罗凯和凯美纳效果良好，但是耐药后，经过基因检测，发现耐药机制为T790M突变导致的继发性耐药的患者。
该药的上市，解决了大部分患者因EGFR靶点耐药导致靶向治疗无效的问题。
知道自己适用AZD9291后，林先生开始寻找购买途径，因为AZD9291还没有国内上市。
经病友推荐，林先生电话咨询了出国就医服务公司——杭州五舟医院管理有限公司。
杭州五舟医学顾问蒋医生在清楚林先生的情况后，表示林先生可以通过与日本医院进行远程视频会诊，购买到AZD9291。
林先生听到可以购买AZD9291，比较开心。
于是向蒋医生详细询问了具体流程。
蒋医生为他解释了每一个步骤：一、双方签订远程视频会诊合同，保障各自的权益;二、需要林先生提供病历资料，杭州五舟医学团队对病历资料进行整理，并撰写病情简述，翻译成日文，在做会诊前要发给日本医院，让日本专家对林先生的病情做一个初步评估;三、确定林先生可以服用AZD9291后，杭州五舟与日本医院约定会诊日期;四、如期举行视频会诊，杭州五舟医学顾问会到林先生家或林先生到杭州五舟公司协助进行视频会诊;五、日本专家开具处方，直接邮寄药物到林先生家。
AZD-9291-SDS-MedChemExpress
Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:Oct.-11-2018Print Date:Oct.-11-20181. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :AZD-9291Catalog No. :HY-15772CAS No. :1421373-65-01.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses :Laboratory chemicals, manufacture of substances.1.3 Details of the supplier of the safety data sheetCompany:MedChemExpress USATel:609-228-6898Fax:609-228-5909E-mail:sales@1.4 Emergency telephone numberEmergency Phone #:609-228-68982. HAZARDS IDENTIFICATION2.1 Classification of the substance or mixtureGHS Classification in accordance with 29 CFR 1910 (OSHA HCS)Acute toxicity, Oral (Category 4)Skin irritation (Category 2)Eye irritation (Category 2A)Specific target organ toxicity, single exposure (Category 3)2.2 GHS Label elements, including precautionary statementsPictogramSignal word WarningHazard statement(s)H302 Harmful if swallowed.H315 Causes skin irritation.H319 Causes serious eye irritation.H335 May cause respiratory irritation.Precautionary statement(s)P261 Avoid breathing dust ⁄ fume ⁄ gas ⁄ mist ⁄ vapours ⁄ spray.P264 Wash skin thoroughly after handling.P270 Do not eat, drink or smoke when using this product.P271 Use only outdoors or in a well-ventilated area.P280 Wear protective gloves ⁄ eye protection ⁄ face protection.P301 + P312 IF SWALLOWED: Call a POISON CENTER or doctor ⁄ physician if you feel unwell.P302 + P352 IF ON SKIN: Wash with plenty of soap and water.P304 + P340 IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing.P305 + P351 + P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do.Continue rinsing.2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms:Osimertinib;Mereletinib;AZD9291;AZD 9291Formula:C28H33N7O2Molecular Weight:499.61CAS No. :1421373-65-04. FIRST AID MEASURES4.1 Description of first aid measuresEye contactRemove any contact lenses, locate eye-wash station, and flush eyes immediately with large amounts of water. Separate eyelids with fingers to ensure adequate flushing. Promptly call a physician.Skin contactRinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician.InhalationImmediately relocate self or casualty to fresh air. If breathing is difficult, give cardiopulmonary resuscitation (CPR). Avoid mouth-to-mouth resuscitation.IngestionWash out mouth with water; Do NOT induce vomiting; call a physician.4.2 Most important symptoms and effects, both acute and delayedThe most important known symptoms and effects are described in the labelling (see section 2.2).4.3 Indication of any immediate medical attention and special treatment neededTreat symptomatically.5. FIRE FIGHTING MEASURES5.1 Extinguishing mediaSuitable extinguishing mediaUse water spray, dry chemical, foam, and carbon dioxide fire extinguisher.5.2 Special hazards arising from the substance or mixtureDuring combustion, may emit irritant fumes.5.3 Advice for firefightersWear self-contained breathing apparatus and protective clothing.6. ACCIDENTAL RELEASE MEASURES6.1 Personal precautions, protective equipment and emergency proceduresUse full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnel to safe areas.Refer to protective measures listed in sections 8.6.2 Environmental precautionsTry to prevent further leakage or spillage. Keep the product away from drains or water courses.6.3 Methods and materials for containment and cleaning upAbsorb solutions with finely-powdered liquid-binding material (diatomite, universal binders); Decontaminate surfaces and equipment by scrubbing with alcohol; Dispose of contaminated material according to Section 13.7. HANDLING AND STORAGE7.1 Precautions for safe handlingAvoid inhalation, contact with eyes and skin. Avoid dust and aerosol formation. Use only in areas with appropriate exhaust ventilation.7.2 Conditions for safe storage, including any incompatibilitiesKeep container tightly sealed in cool, well-ventilated area. Keep away from direct sunlight and sources of ignition.Recommended storage temperature:Powder-20°C 3 years4°C 2 yearsIn solvent-80°C 6 months-20°C 1 monthShipping at room temperature if less than 2 weeks.7.3 Specific end use(s)No data available.8. EXPOSURE CONTROLS/PERSONAL PROTECTION8.1 Control parametersComponents with workplace control parametersThis product contains no substances with occupational exposure limit values.8.2 Exposure controlsEngineering controlsEnsure adequate ventilation. Provide accessible safety shower and eye wash station.Personal protective equipmentEye protection Safety goggles with side-shields.Hand protection Protective gloves.Skin and body protection Impervious clothing.Respiratory protection Suitable respirator.Environmental exposure controls Keep the product away from drains, water courses or the soil. Cleanspillages in a safe way as soon as possible.9. PHYSICAL AND CHEMICAL PROPERTIES9.1 Information on basic physical and chemical propertiesAppearance Light yellow to brown (Solid)Odor No data availableOdor threshold No data availablepH No data availableMelting/freezing point No data availableBoiling point/range No data availableFlash point No data availableEvaporation rate No data availableFlammability (solid, gas)No data availableUpper/lower flammability or explosive limits No data availableVapor pressure No data availableVapor density No data availableRelative density No data availableWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition temperature No data availableViscosity No data availableExplosive properties No data availableOxidizing properties No data available9.2 Other safety informationNo data available.10. STABILITY AND REACTIVITY10.1 ReactivityNo data available.10.2 Chemical stabilityStable under recommended storage conditions.10.3 Possibility of hazardous reactionsNo data available.10.4 Conditions to avoidNo data available.10.5 Incompatible materialsStrong acids/alkalis, strong oxidising/reducing agents.10.6 Hazardous decomposition productsUnder fire conditions, may decompose and emit toxic fumes.Other decomposition products - no data available.11.TOXICOLOGICAL INFORMATION11.1 Information on toxicological effectsAcute toxicityClassified based on available data. For more details, see section 2Skin corrosion/irritationClassified based on available data. For more details, see section 2Serious eye damage/irritationClassified based on available data. For more details, see section 2Respiratory or skin sensitizationClassified based on available data. For more details, see section 2Germ cell mutagenicityClassified based on available data. For more details, see section 2CarcinogenicityIARC: No component of this product present at a level equal to or greater than 0.1% is identified as probable, possible or confirmed human carcinogen by IARC.ACGIH: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by ACGIH.NTP: No component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmed carcinogen by NTP.OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by OSHA.Reproductive toxicityClassified based on available data. For more details, see section 2Specific target organ toxicity - single exposureClassified based on available data. For more details, see section 2Specific target organ toxicity - repeated exposureClassified based on available data. For more details, see section 2Aspiration hazardClassified based on available data. For more details, see section 2Additional informationRTECS No.: UnavailableThis information is based on our current knowledge. However the chemical, physical, and toxicological properties have not been completely investigated.12. ECOLOGICAL INFORMATION12.1 ToxicityNo data available.12.2 Persistence and degradabilityNo data available.12.3 Bioaccumlative potentialNo data available.12.4 Mobility in soilNo data available.12.5 Results of PBT and vPvB assessmentPBT/vPvB assessment unavailable as chemical safety assessment not required or not conducted.12.6 Other adverse effectsNo data available.13. DISPOSAL CONSIDERATIONS13.1 Waste treatment methodsProductDispose substance in accordance with prevailing country, federal, state and local regulations.Contaminated packagingConduct recycling or disposal in accordance with prevailing country, federal, state and local regulations.14. TRANSPORT INFORMATIONDOT (US)This substance is considered to be non-hazardous for transport.IMDGThis substance is considered to be non-hazardous for transport.IATAThis substance is considered to be non-hazardous for transport.15. REGULATORY INFORMATIONSARA 302 Components:No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302.SARA 313 Components:This material does not contain any chemical components with known CAS numbers that exceed the threshold (De Minimis) reporting levels established by SARA Title III, Section 313.SARA 311/312 Hazards:No SARA Hazards.Massachusetts Right To Know Components:No components are subject to the Massachusetts Right to Know Act.Pennsylvania Right To Know Components:No components are subject to the Pennsylvania Right to Know Act.New Jersey Right To Know Components:No components are subject to the New Jersey Right to Know Act.California Prop. 65 Components:This product does not contain any chemicals known to State of California to cause cancer, birth defects, or anyother reproductive harm.16. OTHER INFORMATIONCopyright 2018 MedChemExpress. The above information is correct to the best of our present knowledge but does not purport to be all inclusive and should be used only as a guide. The product is for research use only and for experienced personnel. It must only be handled by suitably qualified experienced scientists in appropriately equipped and authorized facilities. The burden of safe use of this material rests entirely with the user. MedChemExpress disclaims all liability for any damage resulting from handling or from contact with this product.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
阿斯利康抗结核病新药AZD-5847成为全球TB候选药物新化学实体新成员
阿斯利康抗结核病新药AZD-5847成为全球TB候选药物新
化学实体新成员
崔玉彬
【期刊名称】《国外医药（抗生素分册）》
【年(卷),期】2010(031)005
【摘要】@@ 2009年12月,阿斯利康(AstraZeneca)公司研制的其首个结核病(TB)候选药物AZD-5847进入I期临床试验阶段(Phase I).AZD-5847为噁唑烷酮类(oxazolidinones)药物,是继利奈唑胺(linezolid,TB适应症处于Phase II)、PNU-100480(U-100480,处于Phase I)之后的此类候选TB药物.
【总页数】1页(P236)
【作者】崔玉彬
【作者单位】中国医药集团总公司,四川抗菌素工业研究所,成都,610052
【正文语种】中文
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