基于文献计量学分析的免疫性疾病领域药学研究进展

免疫性疾病是全球发病率和死亡率最高的疾病之一,近年来呈上升趋势。免疫性疾病领域药学研究的快速发展推动了治疗免疫性疾 病的药物的研发和上市。采用文献计量的方法从研发趋势、国家分布、机构分布、研究热点等多个角度对全球免疫性疾病领域药学研究的 情况进行分析,为我国治疗免疫性疾病的药物研发和相关政策制定提供参考。     

全球精神疾病治疗药物分析报告（2014）（Ⅱ）

报告采用文献调研、数据库检索、数据统计与分析、专家咨询等定性定量情报研究方法,对全球精神疾病治疗药物研发情况从上市、注册与预注册、临床研究各阶段、发现阶段及暂停撤回终止阶段进行多角度、多层次的分析,旨在为精神疾病治疗药物的研发提供参考。     

全球精神疾病治疗药物分析报告（2014）（I）

报告采用文献调研、数据库检索、数据统计与分析、专家咨询等定性定量情报研究方法,对全球精神疾病治疗药物研发情况从上市、注册与预注册、临床研究各阶段、发现阶段及暂停撤回终止阶段进行多角度、多层次的分析,旨在为精神疾病治疗药物的研发提供参考。     

全球抗HIV 药物研发进展报告

近年来,艾滋病在世界范围内的迅速传播和蔓延,已严重威胁着人类的健康,且引发了一系列社会问题。报告以Thomson Reuters Cortellis 数据库为数据源,从总体研发态势、研发阶段、作用靶点、研究地区、研发机构、销售情况以及交易合作等角度对全球 抗HIV 药物的研发情况进行多角度、多层次的分析,旨在为我国抗HIV 药物的研发提供参考。     

2014 年全球热门药物靶点分析—— IL-6 靶标药物

IL-6 是一种多效性前炎症细胞因子,具有多种生物学活性,包括介导炎症反应、免疫反应等。随着对 IL-6 及其受体信号通路研究 的不断深入,IL-6 现已成为一个有效的治疗靶点,在炎症及自身免疫性疾病的治疗过程中发挥重要作用。采用文献调研、数据库检索、数 据统计与分析等定性定量情报学研究方法,从研发阶段、适应证、临床及上市药物等方面对全球 IL-6 靶标药物的研发情况进行分析,旨在 为我国免疫药物的研发提供参考。     

靶向小分子创新药物

寻找药物新靶点是全球创新药物研究激烈竞争的焦点."组学"、生物信息学、系统生物学、药物筛选现代检测技术等新理论、新技术的发展使新的筛选模型和评价技术不断取得突破.靶向抗肿瘤药物的开发是靶向小分子创新药物的重点任务,多靶点的抗肿瘤药物开发及新靶点的发现是抗肿瘤药物研发的新趋势.     

2001至2005年全球处方药销售和新药研发趋势的分析

分析处方药市场动态和研发趋势将对我国“十一五”生物医药发展战略的确立提供有意义的参考。全球人用处方药市场近5年发展迅速,其销售额连续突破了4000亿、5000亿和6000亿美元等“多零”关节点,已经成为21世纪经济快车的重要引擎之一。世界50强和10强制药企业销售额合计分别占总额的70%～78%和42%～58%;2005年,50强和10强的研发投入分别约为750亿美元和450亿美元。年销售额超过10亿美元的“重磅炸弹”总数为94个,降血脂药物销售稳定地排在首位,抗肿瘤药物近2年增长最快,生物制品连续2年增长率大于17%。新批上市药物呈现了下降趋势。     

全球微生态药物研发现状及发展趋势 *

微生态药物在许多复杂性和慢性疾病中显示出极大的潜力,逐渐成为国际制药行业的新趋势。基于科睿唯安旗下的Cortellis数据库,采用定量分析和专家智慧相结合的方法,从总体研发现状、主要国家/地区、主要适应症、重点企业研发管线、重点在研药物、商业化交易多个维度展现全球微生态药物的研发和商业化全景。分析结果显示:全球共有142个在研微生态药物,其中49个药物处于临床阶段。美国在微生态药物研发和商业化方面遥遥领先,其数量占在研药物总量的70%。在研药物的适应症主要集中于炎症性肠病、艰难梭菌感染、溃疡性结肠炎等肠道感染性疾病。4D pharma公司的在研药物数量最多,微生态药物重点研发企业均建立起核心技术平台。处于临床3期的微生态药物共有7个,全球微生态药物商业化交易共有303起,最大的交易金额是27.8亿美元。未来,微生态药物有望在更难被人类征服的肿瘤和神经系统疾病方面取得突破性进展。     

罕见病领域研究现状与趋势分析

罕见病是指发病率极低的疾病.目前全球约有8000多种罕见病.罕见病的有效防治是建设"健康中国"的重要组成部分.本文分析了全球罕见病领域研究态势及药物研发概况.结果表明,受政策和技术推动,罕见病领域研究呈快速增长趋势;研究热点主要包括罕见病突变基因的鉴定与治疗;技术开发重点主要包括罕见病药物研发、基因治疗病毒载体开发、罕...     

全球单克隆抗体药物研发现状及发展趋势

单克隆抗体药物以其独特的作用机制及高效性,在恶性肿瘤和自身免疫疾病的治疗中发挥了不可估量的重要作用,成为全球的研发热点。基于科睿唯安旗下的Cortellis数据库,采用定量分析和专家智慧相结合的方法,从总体研发和商业化现状、主要国家/地区、技术和种类、靶点及作用机制、市场份额、产品交易多个维度展现出全球单克隆抗体药物的研发和商业化全景。分析结果显示:全球已上市的单克隆抗体药物有133个,其中已上市的人源化单克隆抗体药物占已上市的单克隆抗体药物总数的37. 6%。作用靶点主要集中在HER、TNF、CD20、PD-1/L1、VEGF以及CD3,其中作为HER2酪氨酸激酶受体抑制剂的药物数量最多。美国在单克隆抗体药物研发和商业化方面遥遥领先,中国在研和上市的单抗隆抗体药物总数排名第二,但中国上市的单抗隆抗体药物数量仅8个。2017年销售额高于10亿美元的单克隆抗体药物有22个。全球单克隆抗体药物的交易数量共有1 408次,药物开发与商业化许可是最主要的交易方式。未来,单克隆抗体药物的发展趋势将朝着新靶点、新适应症和新用药方案的方向发展,将会产生更多"重磅炸弹药物"。     

Combination of a Proteomics Approach and Reengineering of Meso Scale Network Models for Prediction of Mode-of-Action for Tyrosine Kinase Inhibitors

In drug discovery, the characterisation of the precise modes of action (MoA) and of unwanted off-target effects of novel molecularly targeted compounds is of highest relevance. Recent approaches for identification of MoA have employed various techniques for modeling of well defined signaling pathways including structural information, changes in phenotypic behavior of cells and gene expression patterns after drug treatment. However, efficient approaches focusing on proteome wide data for the identification of MoA including interference with mutations are underrepresented. As mutations are key drivers of drug resistance in molecularly targeted tumor therapies, efficient analysis and modeling of downstream effects of mutations on drug MoA is a key to efficient development of improved targeted anti-cancer drugs. Here we present a combination of a global proteome analysis, reengineering of network models and integration of apoptosis data used to infer the mode-of-action of various tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) cell lines expressing wild type as well as TKI resistance conferring mutants of BCR-ABL. The inferred network models provide a tool to predict the main MoA of drugs as well as to grouping of drugs with known similar kinase inhibitory activity patterns in comparison to drugs with an additional MoA. We believe that our direct network reconstruction approach, demonstrated on proteomics data, can provide a complementary method to the established network reconstruction approaches for the preclinical modeling of the MoA of various types of targeted drugs in cancer treatment. Hence it may contribute to the more precise prediction of clinically relevant on- and off-target effects of TKIs.     

A method of gene expression data transfer from cell lines to cancer patients for machine-learning prediction of drug efficiency

Personalized medicine implies that distinct treatment methods are prescribed to individual patients according several features that may be obtained from, e.g., gene expression profile. The majority of machine learning methods suffer from the deficiency of preceding cases, i.e. the gene expression data on patients combined with the confirmed outcome of known treatment methods. At the same time, there exist thousands of various cell lines that were treated with hundreds of anti-cancer drugs in order to check the ability of these drugs to stop the cell proliferation, and all these cell line cultures were profiled in terms of their gene expression.

Here we present a new approach in machine learning, which can predict clinical efficiency of anti-cancer drugs for individual patients by transferring features obtained from the expression-based data from cell lines. The method was validated on three datasets for cancer-like diseases (chronic myeloid leukemia, as well as lung adenocarcinoma and renal carcinoma) treated with targeted drugs – kinase inhibitors, such as imatinib or sorafenib.     

全球抗病毒药物研发进展与展望

病毒是危害人体健康的主要病原体之一,病毒感染和传播造成的传染性疾病严重威胁人类健康。目前,艾滋病、病毒性肝炎等发病率高、治愈率低的病毒性疾病仍在全球蔓延,流感病毒、冠状病毒等呼吸道病毒不断发生变异,2019年以来,新冠病毒引起的全球疫情对世界各国产生巨大影响,疫情走向还存在很大不确定性,开发安全有效的抗病毒药物成为应对病毒性疾病的重要手段。拟在总结全球抗病毒药物研发整体现状的基础上,分析抗艾滋病病毒、肝炎病毒、新冠病毒等重点领域的新药研发进展,提出抗病毒药物的发展建议,为未来研发更加高效的抗病毒药物提供指引和参考。     

Haematotoxicology: scientific basis and regulatory aspects

Haematopoietic tissues are the targets of numerous xenobiotics. The purpose of in vitro haematotoxicology is the prediction of adverse haematological effects from toxicants on human haematopoietic targets under controlled experimental conditions in the laboratory. Building on its foundations in experimental haematology and the wealth of haematotoxicological data found in experimental oncology, this field of alternative toxicology has developed rapidly during the past decade. Preclinical and clinical drug development for anti-cancer drugs differs from that for other pharmaceuticals, because of the life-threatening nature of the disease. Treatment with anti-cancer drugs at clinically efficacious doses usually induces serious side-effects. The design of preclinical toxicology studies for anti-cancer drugs is intended to identify a safe clinical starting dose, characterise toxicities that could be encountered in human clinical trials, and determine whether these toxicities are reversible, manageable, and predictable. Although the myeloid colony-forming unit (CFU-GM) progenitor is most frequently evaluated, other defined progenitors and stem cells, as well as cell types found in the marrow stroma, can now be evaluated in vitro. Genetic damage to haematopoietic cells can occur in the absence of any overt haematological signs. The development of tissue-specific screening systems that are able to give information about the toxic effects of chemicals, drugs and environmental hazards on target genes is needed, in order to make preliminary decisions or to set priorities for selection among large groups of chemicals and possible drugs.     

RAS相关通路介导的结直肠癌药物联合治疗的应用

RAS相关信号通路在结直肠癌的发生、发展中起着重要作用，与该类肿瘤细胞的增殖、转移、凋亡密切相关。目前，包括靶向药物、化疗药物的单药治疗对结直肠癌的临床获益并不理想。近年来，在临床试验和临床前研究中RAS相关信号通路的抑制剂与其他药物的联合应用取得了良好效果，其中EGFR抑制剂、VEGF抑制剂、RAS直接抑制剂、MEK抑制剂和RAF抑制剂的表现尤为突出。本文就RAS相关信号通路与结直肠癌的作用关系、临床试验和临床前研究中的联合用药策略以及组合用药的耐药机制研究进行系统性综述，以期为未来临床多药治疗策略奠定基础。     

多肽类药物的研究进展

多肽在包括细胞增殖分化、免疫防御、肿瘤病变等在内的生命活动过程中起着至关重要的作用。自 1953 年首个人工合成的具有生 物活性的多肽问世至今,全球上市的多肽药物有 80 多个,有大量多肽药物进入临床研究。多肽类药物具有独特的优势：活性显著、特异性 强、毒性较弱,在体内不易产生蓄积,与其他药物的相互作用比较少。综述了目前国内外多肽药物的发展情况,希望对从事多肽类药物研 发的同行有所帮助。     

Molnupiravir,favipiravir and other antiviral drugs with proposed potentials for management of COVID-19: a concern on antioxidant aspect

COVID-19 is an important global public health problem that causes millions of infections worldwide. The specific antiviral drug for this new infection is still under research. Some new antiviral drugs, including molnupiravir and favipiravir, are proposed for usefulness in management of COVID-19. Additionally, some classic antiviral drugs used for other viral infections are also reproposed for the potentials for management of COVID-19. In the management of COVID-19, there are several pharmacological actions. An important consideration in antiviral therapy is the management of oxidative stress, which plays important roles in viral infections including to COVID-19. The analysis of antioxidative properties of alternative drugs for management of COVID-19 is interesting and can give basic data for further new antiviral drug researching. Here, the authors perform a molecular analysis on molnupiravir, favipiravir and other antiviral drugs with proposed potentials for management of COVID-19 to determine their antioxidative properties. Data from electron acceptor and donor calculation for each drug is used for further estimating overall antioxidative characteristic. Based on the present study, all studied drugs have overall antioxidative properties. Hence, the advantage of molnupiravir, favipiravir and other antiviral drugs with proposed potentials for the management of COVID-19 is their direct action on viral molecule via binding-blocking process as well as antixodiative process. For management of COVID-19 antioxidative stress, other non-antiviral drugs that are proposed for clinical advantage might also be useful.     

药（毒）物对尸食性蝇类生长发育影响的研究进展

药（毒）物对尸食性蝇类生长发育影响是法医昆虫毒理学领域里一个十分重要的研究方向,其研究结果可对与药（毒）物相关死亡案件的死亡时间作出修正。随着近年来全球毒品及药物滥用情况的日趋严重,其所导致的死亡案件也越来越多。这类案件常常需要应用尸食性蝇类生长发育历期来推算死后经历时间（postmortem interval, PMI）。为了阐明该领域的研究进展以及未来研究的焦点和难点,本文在阐述法医昆虫毒理学概念和特点的基础上,按照不同的药（毒）物分类,对近年来药（毒）物对尸食性蝇类生长发育影响在国内外的研究进展进行了综述。研究表明,某些药（毒）物对尸食性蝇类生长发育具有一定的影响,且这种影响存在种属差异。目前,该领域的研究尚限于宏观现象观察阶段,其研究范围在不断拓宽,既有的研究也在进一步深化,但还有许多问题有待进一步探讨。