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《Expert opinion on emerging drugs》2013,18(1):31-44
Introduction: Thromboembolic disease encompasses a spectrum of conditions extending from deep vein thrombosis to stroke and myocardial infarction. The current anticoagulation therapy is cumbersome and characterized by several important drawbacks. Areas covered: Existing treatments and latest breakthroughs on emerging anticoagulants are presented. Oral and parenteral novel anticoagulants are being developed and tested for efficacy and safety and results are being published regularly. The introduction of novel anticoagulants marks a new era in the management of anticoagulated patients. It is important for the healthcare provider to understand the benefits and risks of the armamentarium of anticoagulants that will be available in the very near future. The critical conclusions drawn will help the reader look past what is the most highlighted feature of the new anticoagulantion era: the non-necessity for monitoring. Expert opinion: Currently, novel anticoagulants seem to lack the indefinable ‘charm’ of weakness. However, important questions remain unanswered and will require in-depth evaluations. 相似文献
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《Expert opinion on therapeutic patents》2013,23(11):1603-1613
Background: RNA and DNA aptamers recognize their targets with high specificity and affinity. These aptamers can be developed against almost any target protein through iterative cycles of in vitro screening of a combinatorial oligonucleotide library for target binding. Aptamer sequences from the final pool of in vitro selection are screened for pharmacological activity and possible medical applications. Methods: Chemical modifications and improvements of the identification of aptamer selection procedures made aptamers rival antibodies in diagnostic and therapeutic applications. This article reviews recent literature and patents and discusses the properties of aptamers as high-affinity and specificity target binders as well as their stability in biological fluids that turns them into therapeutic agents. Conclusion: The development of aptamers into compounds with therapeutic and diagnostic compounds has resulted in patents protecting the sequences and the use of these oligonucleotides. Several of these patented aptamers are currently being tested in Phase I or II clinical trials. Moreover, an anti-VEGF aptamer has already been approved by the FDA for treatment of age-related macular degeneration in humans. 相似文献
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《Expert opinion on drug discovery》2013,8(9):1205-1224
Nucleic acid aptamers, like monoclonal antibodies, bind to their target molecule with high affinity and specificity. Owing to their molecular recognition properties that are based on their three-dimensional structure, aptamers have been used as powerful tools in various fields, such as detection, separation or purification of target molecules. In addition, their intrinsic characteristics make aptamers excellent candidates for therapeutic applications. Due to their high specificity, stability, low toxicity and apparent non-immunogenicity, they provide viable alternatives to antibody- and small molecule-based therapeutics. Unlike antibodies, they can be generated against toxic, unstable or difficult to purify proteins. Furthermore, they can be chemically derivatised to extend their bioavailability and lifetimes in biological fluids, and they even offer the possibility for fast and efficient regulation. Similar to other therapeutic nucleic acids, such as antisense oligonucleotides, ribozymes or siRNA, problems with cellular uptake and susceptibility to nucleolytic attack have to be overcome for their successful application. With the first aptamer-based drug having entered the market and a few in Phase II trials, the road has been paved for more to follow. In this review, the requirements and properties of therapeutic aptamers are discussed and the recent progress in aptamer research towards drug development is highlighted. 相似文献
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Summary. The evolution of platelet directed pharmacotherapy in the prevention and treatment of patients with thrombotic disorders is based soundly on a rapidly expanding knowledge of platelet biology. Traditionally viewed, throughout most of its relatively brief history in medicine, as an anucleate, passive contributor to hemostasis, a more contemporary perspective acknowledges platelets as complex, multidimensional cells that participate actively in coagulation, vascular repair, angiogenesis and thrombosis within the micro and the macro-circulatory systems. Herein, we consider platelet-directed pharmacotherapy from these fundamental, biology-based exemplars—megakaryocytes, signal transduction and the platelet—coagulation protease interface. We also highlight the emerging biopharmacology platform of oligonucleotide platelet adhesion antagonists and their complementary antidotes. 相似文献
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《Expert opinion on drug discovery》2013,8(1):75-87
Importance of the field: Therapeutic aptamers are synthetic, structured oligonucleotides that bind to a very broad range of targets with high affinity and specificity. They are an emerging class of targeting ligand that show great promise for treating a number of diseases. A series of aptamers currently in various stages of clinical development highlights the potential of aptamers for therapeutic applications. Areas covered in this review: This review covers in vitro selection of oligonucleotide ligands, called aptamers, from a combinatorial library using the Systematic Evolution of Ligands by Exponential Enrichment process as well as the other known strategies for finding aptamers against various targets. What the reader will gain: Readers will gain an understanding of the highly useful strategies for successful aptamer discovery. They may also be able to combine two or more of the presented strategies for their aptamer discovery projects. Take home message: Although many processes are available for discovering aptamers, it is not easy to discover an aptamer candidate that is ready to move toward pharmaceutical drug development. It is also apparent that there have been relatively few therapeutic advances and clinical trials undertaken due to the small number of companies that participate in aptamer development. 相似文献
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Nucleic acids are increasingly being considered for therapeutic uses, either to interfere with the function of specific nucleic acids or to bind specific proteins. Three types of nucleic acid drugs are discussed in this review: aptamers, compounds which bind specific proteins; triplex forming (antigene) compounds; which bind double stranded DNA; and ribozymes (catalytic RNA), which bind and cleave RNA targets. The binding of aptamers to protein may involve specific sequence recognition, although this is not always the case. The interaction of triplex forming oligonucleotides or ribozymes with their targets always involves specific sequence recognition and hybridization. Early optimism concerning the possibility of designing drugs without a priori knowledge of the structure of the target (except a nucleotide sequence) has been tempered by the finding that target structure has a dramatic effect upon the hybridization potential of the nucleic acid drug. Other obstacles to the creation of effective nucleic acid drugs are their relative high molecular weight (>3300) and their sensitivity to degradation. The molecular weight of these compounds has created a significant delivery problem which needs to be solved if nucleic acid drugs are to become effective therapies. 相似文献
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目的筛选出与心肌肌钙蛋白I(cTnI)具有高亲和力和高特异性的核酸适配体,为诊断急性心肌梗死(AMI)提供实验基础。方法采用基于乳液PCR(ePCR)的SELEX技术筛选出能与cTnI特异性结合的3个适配体,并对ePCR条件进行优化,对适配体进行亲和力(Kd值)测定并与市售cTnI抗体进行比较,选出Kd值最小的适配体,进行特异性鉴定。结果SELEX过程中通过优化得到ePCR最佳条件,筛选得到的3个适配体均对cTnI具有较强的亲和力,其Kd值范围为2.04~16.85 nmol/L,其中适配体Apt-1的亲和力最强[Kd为(2.04±0.11) nmol/L]且优于市售抗体,特异性高,敏感性强,不与其他相关蛋白有非特异性结合。结论筛选出的适配体Apt-1能与cTnI产生高亲和力的特异性结合,可进一步用于临床样本中cTnI的检测。 相似文献