Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan.
Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan.
Bioorg Med Chem. 2021 Jul 1;41:116221. doi: 10.1016/j.bmc.2021.116221. Epub 2021 May 19.
Chemical knockdown of therapeutic targets using proteolysis targeting chimeras (PROTACs) is a rapidly developing field in drug discovery, but PROTACs are bifunctional molecules that generally show poor bioavailability due to their relatively high molecular weight. Recent developments aimed at the development of next-generation PROTACs include the in vivo synthesis of PROTAC molecules, and the exploitation of PROTACs as chemical tools for in vivo synthesis of ubiquitinated proteins. This short review covers recent advances in these areas and discusses the prospects for in vivo synthetic PROTAC technology.
利用蛋白水解靶向嵌合体（PROTACs）对治疗靶点进行化学敲低是药物发现中一个快速发展的领域，但 PROTACs 是双功能分子，由于其相对较高的分子量，通常表现出较差的生物利用度。最近的发展旨在开发下一代 PROTACs，包括 PROTAC 分子的体内合成，以及将 PROTACs 用作体内合成泛素化蛋白的化学工具。这篇简短的综述涵盖了这些领域的最新进展，并讨论了体内合成 PROTAC 技术的前景。
