TetraGenetics Inc., 91 Mystic Street, Arlington, MA 02474, USA.
TetraGenetics Inc., 91 Mystic Street, Arlington, MA 02474, USA.
Trends Pharmacol Sci. 2021 Aug;42(8):657-674. doi: 10.1016/j.tips.2021.05.006.
Integral membrane proteins (MPs) are important drug targets across most fields of medicine, but historically have posed a major challenge for drug discovery due to difficulties in producing them in functional forms. We review the state of the art in drug discovery strategies using recombinant multipass MPs, and outline methods to successfully express, stabilize, and formulate them for small-molecule and monoclonal antibody therapeutics development. Advances in structure-based drug design and high-throughput screening are allowing access to previously intractable targets such as ion channels and transporters, propelling the field towards the development of highly specific therapies targeting desired conformations.
整合膜蛋白（MPs）是医学领域大多数药物靶点的重要组成部分，但由于其在功能形式下的产生存在困难，因此在历史上一直对药物发现构成重大挑战。我们回顾了使用重组多跨 MP 进行药物发现策略的最新技术，并概述了成功表达、稳定和配制它们用于小分子和单克隆抗体治疗药物开发的方法。基于结构的药物设计和高通量筛选的进展使得以前难以处理的靶点（如离子通道和转运蛋白）得以进入，推动该领域朝着针对所需构象的高度特异性治疗方法的开发方向发展。
