Seavey Matthew M, Lu Lily D, Stump Kristine L
Worldwide Discovery Research, Cephalon, Inc., West Chester, Pennsylvania, USA.
Curr Protoc Pharmacol. 2011 Jun;Chapter 5:Unit 5.60. doi: 10.1002/0471141755.ph0560s53.
Systemic Lupus Erythematosus (SLE) is a debilitating and often fatal autoimmune disease that involves multiple organ systems. It can develop for years before being diagnosed. Current treatments for SLE usually involve the use of cytotoxic or immunosuppressive agents that can lead to infection or cancer. The design of appropriate models and assays will determine the efficiency and speed with which an investigator can test a new chemical entity (NCE) or expect results to move a drug discovery program forward. This unit describes a series of preclinical assays for the identification of new agents for the treatment of SLE. Most importantly, this unit will guide the reader through a step-by-step process to select appropriate models, validation drugs, and readouts, depending on the objective of the study. The reader will acquire a working knowledge of what models are available and the potential advantages and disadvantages of each, including ex vivo assays relevant to the discovery of new SLE therapeutics.
系统性红斑狼疮（SLE）是一种使人衰弱且往往致命的自身免疫性疾病，累及多个器官系统。它可能在被诊断之前数年就已发病。目前针对SLE的治疗通常涉及使用细胞毒性或免疫抑制药物，这些药物可能导致感染或癌症。合适模型和检测方法的设计将决定研究人员测试新化学实体（NCE）或期望推动药物研发项目取得成果的效率和速度。本单元描述了一系列用于鉴定治疗SLE新药物的临床前检测方法。最重要的是，本单元将根据研究目的，引导读者逐步选择合适的模型、验证药物和读数。读者将获得关于现有哪些模型以及每种模型潜在优缺点的实用知识，包括与新SLE治疗药物发现相关的体外检测方法。
