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抗体药物偶联物生物信息学:通过信箱进行药物传递。

Antibody Drug Conjugate bioinformatics: drug delivery through the letterbox.

机构信息

Bioinformatics & Medical Informatics Team, Biomedical Research Foundation, Academy of Athens, Soranou Efessiou 4, 11527 Athens, Greece.

出版信息

Comput Math Methods Med. 2013;2013:282398. doi: 10.1155/2013/282398. Epub 2013 Jun 19.

Abstract

Antibodies appear to be the first line of defence in the adaptive immune response of vertebrates and thereby are involved in a multitude of biochemical mechanisms, such as regulation of infection, autoimmunity, and cancer. It goes without saying that a full understanding of antibody function is required for the development of novel antibody-interacting drugs. These drugs are the Antibody Drug Conjugates (ADCs), which are a new type of targeted therapy, used for example for cancer. They consist of an antibody (or antibody fragment such as a single-chain variable fragment [scFv]) linked to a payload drug (often cytotoxic). Because of the targeting, the side effects should be lower and give a wider therapeutic window. Overall, the underlying principle of ADCs is to discern the delivery of a drug that is cytotoxic to a target that is cancerous, hoping to increase the antitumoural potency of the original drug by reducing adverse effects and side effects, such as toxicity of the cancer target. This is a pioneering field that employs state-of-the-art computational and molecular biology methods in the fight against cancer using ADCs.

摘要

抗体似乎是脊椎动物适应性免疫反应的第一道防线,因此参与了许多生化机制,如感染、自身免疫和癌症的调节。不言而喻,为了开发新型抗体相互作用药物,需要充分了解抗体的功能。这些药物是抗体药物偶联物 (ADC),这是一种新型的靶向治疗药物,例如用于癌症治疗。它们由抗体(或抗体片段,如单链可变片段 [scFv])与有效载荷药物(通常是细胞毒性药物)连接而成。由于具有靶向性,副作用应该更低,并提供更宽的治疗窗口。总体而言,ADC 的基本原理是辨别将具有细胞毒性的药物递送至癌性靶标,希望通过降低不良反应和副作用(如癌症靶标的毒性)来提高原始药物的抗肿瘤效力。这是一个开创性的领域,在使用 ADC 对抗癌症时采用了最先进的计算和分子生物学方法。

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本文引用的文献

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The application of quantum mechanics in structure-based drug design.量子力学在基于结构的药物设计中的应用。
Expert Opin Drug Discov. 2013 Mar;8(3):263-76. doi: 10.1517/17460441.2013.752812. Epub 2013 Jan 7.
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Pharmacokinetic considerations for antibody drug conjugates.抗体药物偶联物的药代动力学考虑因素。
Pharm Res. 2012 Sep;29(9):2354-66. doi: 10.1007/s11095-012-0800-y. Epub 2012 Jun 28.
9
Antibody-drug conjugates - a perfect synergy.抗体偶联药物——完美的协同作用。
Expert Opin Biol Ther. 2012 Sep;12(9):1191-206. doi: 10.1517/14712598.2012.693473. Epub 2012 Jun 1.
10
Antibody-drug conjugates: basic concepts, examples and future perspectives.抗体偶联药物:基本概念、实例与未来展望。
J Control Release. 2012 Jul 20;161(2):422-8. doi: 10.1016/j.jconrel.2012.01.026. Epub 2012 Jan 28.

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