Ricklin Daniel, Lambris John D
Department of Pathology and Laboratory Medicine, University of Pennsylvania, 401 Stellar Chance, 422 Curie Blvd, Philadelphia, PA, 19104-6100, USA,
Adv Exp Med Biol. 2013;735:1-22. doi: 10.1007/978-1-4614-4118-2_1.
The past few years have proven to be a highly successful and exciting period for the field of complement-directed drug discovery and development. Driven by promising experiences with the first marketed complement drugs, increased knowledge about the involvement of complement in health and disease, and improvements in structural and analytical techniques as well as animal models of disease, the field has seen a surge in creative approaches to therapeutically intervene at various stages of the cascade. An impressive panel of compounds that show promise in clinical trials is meanwhile being lined up in the pipelines of both small biotechnology and big pharmaceutical companies. Yet with this new focus on complement-targeted therapeutics, important questions concerning target selection, point and length of intervention, safety, and drug delivery emerge. In view of the diversity of the clinical disorders involving abnormal complement activity or regulation, which include both acute and chronic diseases and affect a wide range of organs, diverse yet specifically tailored therapeutic approaches may be needed to shift complement back into balance. This chapter highlights the key changes in the field that shape our current perception of complement-targeted drugs and provides a brief overview of recent strategies and emerging trends. Selected examples of complement-related diseases and inhibitor classes are highlighted to illustrate the diversity and creativity in field.
过去几年已证明是补体导向药物发现与开发领域极为成功且令人兴奋的时期。受首批上市补体药物的良好经验、对补体在健康与疾病中所涉作用的认识增加、结构与分析技术以及疾病动物模型的改进所推动，该领域在治疗性干预补体级联反应不同阶段的创新方法方面出现了激增。与此同时，一大批在临床试验中显示出前景的化合物正排列在小型生物技术公司和大型制药公司的研发流程中。然而，随着对补体靶向疗法的这一新关注，有关靶点选择、干预点和时长、安全性以及药物递送等重要问题也随之出现。鉴于涉及补体活性或调节异常的临床病症具有多样性，包括急性和慢性疾病且影响多种器官，可能需要多种但经过专门定制的治疗方法才能使补体恢复平衡。本章重点介绍了该领域的关键变化，这些变化塑造了我们目前对补体靶向药物的认知，并简要概述了近期的策略和新出现的趋势。文中突出了补体相关疾病和抑制剂类别的选定实例，以说明该领域的多样性和创新性。
