急性髓系白血病靶向药物治疗新进展

急性髓系白血病(AML)是一种髓系细胞恶性克隆性疾病。近年来, 新型靶向药物的出现使癌症治疗发生了革命性变化, 有望在AML治疗上取得突破性进展。这些新药包括二代DNA甲基转移酶抑制剂、靶向B细胞淋巴瘤因子2(BCL-2)抑制剂、FMS样酪氨酸激酶3(FLT3)抑制剂、异柠檬酸脱氢酶抑制剂、抗CD33单克隆抗体、Smoothened Inhibitor(SMO)抑制剂、肿瘤蛋白p53靶向药物、抗CD47单抗、核输出蛋白1(XPO1)抑制剂等。本文就AML最新靶向治疗药物作一综述。     

非小细胞肺癌分子靶向治疗的最新研究进展

随着肿瘤生物学、基因组学和分子生物学的发展,靶向治疗的研究和临床应用已成为当前肺癌领域的热点。本文对国内外有关非小细胞肺癌分子靶向治疗的靶点和主要药物进行了综述。首先概括了表皮生长因子受体抑制剂,其次总结了肿瘤血管生成抑制剂,包括抗血管内皮生长因子单克隆抗体、血管内皮抑素和金属蛋白酶抑制剂的研究,最后对新的靶点EML4-ALK抑制剂的研发进行了跟踪。未来肺癌靶向治疗药物的开发和临床应用会达到更加成熟的阶段。     

抗疱疹病毒药物化学研究新进展

目前临床使用最广泛的抗疱疹病毒药物为阿昔洛韦(acyclovir, ACV)及其衍生物,但耐药性问题的出现迫使人们不断寻找新的抗疱疹病毒药物。随着疱疹病毒的生物学特征和致病机制的深入研究以及新药设计与筛选技术的快速发展,越来越多的抗疱疹病毒新靶标和新抑制剂被发现,这使疱疹感染疾病的治疗有了更多选择。本综述总结了近年来在抗疱疹病毒药物研究领域的代表性研究成果。     

非小细胞肺癌靶向药物的开发研究进展

根据美国药物研究与生产商协会(PhRMA)的报告和《新药数据库》等公布的信息,对目前国际上进入III期临床试验的16种非小细胞肺癌(NSCLC)靶向新药进行分析。参照国内相关文献和美国国立癌症研究所对靶向药物的分类,将这16种新药分为EGFR靶向药物、VEGF靶向药物、多靶点抑制剂,新靶点抑制剂。经进一步分析和总结,进入III期临床试验的NSCLC靶向新药主要有以下3个特点:一是呈现多样化,多靶点抑制剂和新靶点抑制剂占87.5%;二是治疗性疫苗崭露头角,治疗性疫苗在未来几年内有可能成为抗NSCLC药物中的新成员;三是将已获得批准用于其他癌症的靶向药物用于治疗NSCLC的临床试验。说明国际制药公司充分利用现有资源开发出更多的抗NSCLC药物。     

21世纪风湿免疫病的生物治疗

生物靶向治疗是21世纪以来风湿免疫病治疗的重大进展。目前已上市的包括肿瘤坏死因子抑制剂、抗CD20单抗和CTLA-4Ig,正在临床试验阶段的药物有抗CD22单抗、抗BLyS单抗和抗白介素-6受体抗体。本文对上述药物的种类、疗效和不良反应进行了综述。     

小细胞肺癌靶向治疗研究进展

小细胞肺癌是一种生长快、易转移的肺神经内分泌肿瘤,约占肺癌发病总数的15%。临床上治疗小细胞肺癌一般采用放化疗结合,在治疗初期通常响应良好,但病人很快产生耐药和复发。早期开发的靶向药物的临床测试均不太理想,迫切需要新的靶向药物和有效的治疗手段。近年来,随着对小细胞肺癌病理机制的深入了解和转化研究,开发了多种针对小细胞肺癌遗传变异的靶向药物,如激酶抑制剂、血管生成抑制剂、凋亡通路抑制剂、蛋白酶体抑制剂、表观遗传抑制剂、免疫检查点抑制剂等。部分靶向治疗正在进行临床试验,同时多种针对小细胞肺癌的新型治疗策略如免疫治疗和联合用药也值得关注。该文总结小细胞肺癌的分子机制和靶向药物的研究进展,以及在此基础上已完成、正在开展的临床研究和临床前研究的现状,同时展望未来可能的小细胞肺癌新型治疗策略。     

三阴性乳腺癌靶向治疗研究进展

三阴性乳腺癌（TNBC）作为乳腺癌一种预后较差的亚型,在出现化疗药物抵抗的情况下,由于缺少其他有效治疗方法,疾病往往易快速复发转移。因此针对TNBC新治疗靶点及靶向药物的研究已成为目前国内外研究热点。本文主要针对目前TNBC靶向治疗研究进展进行总结分析,主要包括ADP合同聚合酶抑制剂、抗血管生成靶向药物、抗表皮生长因子受体信号通路靶向药物、雄激素受体拮抗剂、免疫检查点抑制剂、PI3K-AKT-mTOR通路抑制剂等,以期从中找出最有可能成为未来发展方向的靶向治疗方法。     

抗阿尔茨海默病的胆碱酯酶抑制剂研究进展

目前抗阿尔茨海默病的新策略之一是设计具有多靶向的药物。综述抗阿尔茨海默病的胆碱酯酶抑制剂研究的新进展,分类介绍乙酰胆碱酯酶和丁酰胆碱酯酶双重抑制剂、可抑制B-淀粉样蛋白聚集的胆碱酯酶抑制剂、具有抗氧化作用的胆碱酯酶抑制剂、可拮抗H,受体的胆碱酯酶抑制剂以及NO供体型胆碱酯酶抑制剂等多靶向药物,并讨论了各类药物的设计和优化。     

新型冠状病毒(2019-nCoV)的靶向药物研究策略

新型冠状病毒尚无特效药。新型冠状病毒靶向药物研发面临诸多挑战,其药物研发策略包括筛选广谱抗病毒药,老药新用,以及开发特异的全新药。药物既可抑制病毒靶点(如蛋白酶、合成酶、树突蛋白及病毒壳膜),又可靶向宿主(如病毒受体抑制剂、病毒内吞和跨膜蛋白酶抑制剂等)。最近核糖核酸合成酶抑制剂瑞德西韦在孤例重症患者表现出良好疗效,广谱病毒蛋白酶抑制剂克力芝也在临床上应用。这两种药刚启动III期临床试验,以评价其安全性和有效性。多种药物联用也是当前针对新型冠状病毒的一个主要策略,但应遵从科学依据和临床需求。通过大量文献和多种数据库检索,针对病毒和宿主细胞的关键成药靶点,作者挑选出75个临床在研的靶向药物,包括20个上市药,以助力临床前、临床试验研究和药物改良。     

非小细胞肺癌靶向治疗的药物与临床研究

目的：介绍非小细胞肺癌靶向治疗的药物与临床研究进展。方法：采用近期国内外相关文献进行综述。结果：作用于表皮生长因子受体药物和抗血管生成药物以及环氧合酶抑制剂的临床运用，生存期和症状得到改善。结论：随着医学分子生物学技术和理论的进展，针对肺癌发病机制的靶向分子生物学研究，为肺癌治疗开辟了新的途径。     

Anti-herpesvirus agents: a patent and literature review (2003 to present)

Introduction: The standard therapy used to treat herpesvirus infections is based on the application of DNA polymerase inhibitors such as ganciclovir or aciclovir. Unfortunately, all of these compounds exhibit relatively high toxicity and the mutation of herpesviruses results in the appearance of new drug-resistant strains. Consequently, there is a great need for the development of new, effective and safe anti-herpesvirus agents that employ different patterns of therapeutic action at various stages of the virus life cycle.

Areas covered: Patents and patent applications concerning the development of anti-herpesvirus agents displaying different mechanisms of action that have been published since 2003 are reviewed. In addition, major discoveries in this field that have been published in academic papers have also been included.

Expert opinion: Among all the anti-herpesvirus agents described in this article, the inhibitors of viral serine protease seem to present one of the most effective/promising therapeutics. Unfortunately, the practical application of these antiviral agents has not yet been proven in any clinical trials. Nevertheless, the dynamic and extensive work on this subject gives hope that a new class of anti-herpesvirus agents aimed at the enzymatic activity of herpesvirus serine protease may be developed.     

The DNA helicase–primase complex as a target for herpes viral infection

Introduction: The Herpesviridae are responsible for debilitating acute and chronic infections, and some members of this family are associated with human cancers. Conventional anti-herpesviral therapy targets the viral DNA polymerase and has been extremely successful; however, the emergence of drug-resistant virus strains, especially in neonates and immunocompromised patients, underscores the need for continued development of anti-herpes drugs. In this article, we explore an alternative target for antiviral therapy, the HSV helicase/primase complex.

Areas covered: This review addresses the current state of knowledge of HSV DNA replication and the important roles played by the herpesvirus helicase– primase complex. In the last 10 years several helicase/primase inhibitors (HPIs) have been described, and in this article, we discuss and contrast these new agents with established inhibitors.

Expert opinion: The outstanding safety profile of existing nucleoside analogues for α-herpesvirus infection make the development of new therapeutic agents a challenge. Currently used nucleoside analogues exhibit few side effects and have low occurrence of clinically relevant resistance. For HCMV, however, existing drugs have significant toxicity issues and the frequency of drug resistance is high, and no antiviral therapies are available for EBV and KSHV. The development of new anti-herpesvirus drugs is thus well worth pursuing especially for immunocompromised patients and those who develop drug-resistant infections. Although the HPIs are promising, limitations to their development into a successful drug strategy remain.     

HIV co-receptor inhibitors as novel class of anti-HIV drugs

Entry inhibitors constitute a new class of drugs to treat infection by human immunodeficiency virus type 1 (HIV-1). The first member of this class, enfuvirtide, previously known as T-20 and targeting gp41, has now been licensed for therapeutic use. Several other entry inhibitors are in various stages of pre-clinical or clinical development. In this review we focus on the chemokine receptor inhibitors targeting CCR5 and CXCR4 that are the main HIV co-receptors for viral entry.     

靶向ALK抑制剂的研究进展及前景

随着分子生物医学研究的不断深入,以与肿瘤发生、发展相关的驱动基因为靶点,研发新的药物进行精准的个体化分子靶向治疗,已经成为肿瘤研究的新热点。间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)基因是一种跨膜受体酪氨酸激酶,可在多种恶性肿瘤中发生变异或与其他癌基因融合,是肿瘤的致癌驱动基因。近年来,ALK抑制剂在抗肿瘤、尤其是靶向肺癌方面的研究和应用一直保持了很高的研发热度。笔者针对已开发和在研的新型靶向ALK抑制剂的化学结构、研发进展、临床应用等方面进行了综述,并展望了ALK抑制剂的发展前景和需要解决的问题。     

Development of drugs for Epstein-Barr virus using high-throughput in silico virtual screening

Importance of the field: Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is causally associated with endemic forms of Burkitt's lymphoma, nasopharyngeal carcinoma and lymphoproliferative disease in immunosuppressed individuals. On a global scale, EBV infects > 90% of the adult population and is responsible for ～ 1% of all human cancers. To date, there is no efficacious drug or therapy for the treatment of EBV infection and EBV-related diseases. Areas covered in this review: In this review, we discuss the existing anti-EBV inhibitors and those under development. We discuss the value of different molecular targets, including EBV lytic DNA replication enzymes as well as proteins that are expressed exclusively during latent infection, such as EBV nuclear antigen 1 (EBNA-1) and latent membrane protein 1. As the atomic structure of the EBNA-1 DNA binding domain has been described, it is an attractive target for in silico methods of drug design and small molecule screening. We discuss the use of computational methods that can greatly facilitate the development of novel inhibitors and how in silico screening methods can be applied to target proteins with known structures, such as EBNA-1, to treat EBV infection and disease. What the reader will gain: The reader is familiarized with the problems in targeting of EBV for inhibition by small molecules and how computational methods can greatly facilitate this process. Take home message: Despite the impressive efficacy of nucleoside analogs for the treatment of herpesvirus lytic infection, there remain few effective treatments for latent infections. As EBV latent infection persists within and contributes to the formation of EBV-associated cancers, targeting EBV latent proteins is an unmet medical need. High-throughput in silico screening can accelerate the process of drug discovery for novel and selective agents that inhibit EBV latent infection and associated disease.     

以乙肝病毒核衣壳为靶标的二氢嘧啶类化合物及其作用机制研究进展

核衣壳是乙肝病毒(HBV)的核心结构,在HBV复制感染中起到了重要作用。以核衣壳为靶标的二氢嘧啶类化合物(HAPs)是一类全新结构的高活性HBV抑制剂,有望成为一种新型的乙型肝炎治疗药物。本文就HAPs类化合物的结构特点及其抗乙肝作用机制的研究进展进行综述。     

靶向蛋白非催化功能的药物开发新策略

靶向蛋白催化功能的小分子抑制剂具有特异性差和临床副作用多等缺点,靶向蛋白的非催化功能在药物开发中具有较大的潜力。鉴于靶向蛋白非催化功能抑制剂的广阔的应用前景,对靶向蛋白非催化功能的抑制剂开发新策略即非催化功能结构域策略、变构调控策略和蛋白-蛋白相互作用策略进行总结,同时对其存在的问题和应用前景进行展望,以期为靶向蛋白非催化功能的药物开发提供方向。     

骨髓增生异常综合征治疗药物的研究进展

骨髓增生异常综合征是一组影响骨髓造血干细胞、祖细胞的克隆性疾病.近年来,随着对骨髓增生异常综合征发病机制的深入研究产生了许多新型药物.目前对骨髓增生异常综合征治疗的药物包括缺氧诱导因子脯氨酰羟化酶抑制剂、端粒酶抑制剂、剪切体抑制剂、异柠檬酸脱氢酶抑制剂、新型去甲基化剂、免疫检测点抑制剂、针对TP53突变药物、酪氨酸激酶...     

抗呼吸道合胞病毒候选药物的研究进展

呼吸道合胞病毒(RSV)感染是引发婴幼儿细支气管炎、肺炎的主要病因之一,会导致严重的呼吸系统疾病,会增加罹患哮喘的风险。帕利珠单抗和利巴韦林可用于预防和治疗RSV感染,两者均推荐用于RSV感染风险最高的患者,但其有益作用尚有争议。抗RSV药物的研究主要集中于不同的作用机制如抑制病毒融合、靶向非融合靶点和靶向病毒宿主的抑制剂。因此,预防或治疗呼吸道合胞病毒感染,深入研究抗病毒策略,指导候选药物筛选尤显突出,但是至今仍没有抗病毒药物或疫苗被批准用于RSV感染的治疗或预防。随着病毒学的深入研究,研究者将开发针对病毒靶点蛋白或宿主细胞因子的一系列的抗病毒药物,这些药物研发将为抗病毒提供新的途径。