Minter Ralph R, Sandercock Alan M, Rust Steven J
Department of Antibody Discovery and Protein Engineering, MedImmune, Milstein Building, Granta Park, Cambridge CB21 6GH, UK.
Department of Antibody Discovery and Protein Engineering, MedImmune, Milstein Building, Granta Park, Cambridge CB21 6GH, UK.
Drug Discov Today Technol. 2017 Mar;23:83-90. doi: 10.1016/j.ddtec.2017.03.004. Epub 2017 Apr 25.
The majority of antibody therapeutics have been isolated from target-led drug discovery, where many years of target research preceded drug program initiation. However, as the search for validated targets becomes more challenging and target space becomes increasingly competitive, alternative strategies, such as phenotypic drug discovery, are gaining favour. This review highlights successful examples of antibody phenotypic screens that have led to clinical drug candidates. We also review the requirements for performing an effective antibody phenotypic screen, including antibody enrichment and target identification strategies. Finally, the future impact of phenotypic drug discovery on antibody drug pipelines will be discussed.
大多数抗体疗法是从以靶点为导向的药物发现中分离出来的，在启动药物研发项目之前，需要进行多年的靶点研究。然而，随着寻找经过验证的靶点变得更具挑战性，靶点领域的竞争日益激烈，诸如表型药物发现等替代策略正越来越受到青睐。本综述重点介绍了已促成临床候选药物的抗体表型筛选的成功案例。我们还回顾了进行有效抗体表型筛选的要求，包括抗体富集和靶点识别策略。最后，将讨论表型药物发现对抗体药物研发流程的未来影响。
