Liu Jing, Peng Yunhua, Wei Wenyi
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Front Cell Dev Biol. 2021 Jul 19;9:678077. doi: 10.3389/fcell.2021.678077. eCollection 2021.
PROteolysis-TArgeting Chimeras (PROTACs) is an emerging and promising approach to target intracellular proteins for ubiquitination-mediated degradation, including those so-called undruggable protein targets, such as transcriptional factors and scaffold proteins. To date, plenty of PROTACs have been developed to degrade various disease-relevant proteins, such as estrogen receptor (ER), androgen receptor (AR), RTK, and CDKs. However, the on-target off-tissue and off-target effect is one of the major limitation that prevents the usage of PROTACs in clinic. To this end, we and several other groups have recently developed light-controllable PROTACs, as the representative for the third generation controllable PROTACs, by using either photo-caging or photo-switch approaches. In this review, we summarize the emerging light-controllable PROTACs and the prospective for other potential ways to achieve temporospatial control of PROTACs.
蛋白酶靶向嵌合体（PROTACs）是一种新兴且有前景的方法，用于靶向细胞内蛋白质以进行泛素化介导的降解，包括那些所谓的“不可成药”蛋白质靶点，如转录因子和支架蛋白。迄今为止，已经开发出大量PROTACs来降解各种与疾病相关的蛋白质，如雌激素受体（ER）、雄激素受体（AR）、受体酪氨酸激酶（RTK）和周期蛋白依赖性激酶（CDKs）。然而，靶点上的组织非靶向效应和脱靶效应是阻碍PROTACs在临床应用的主要限制之一。为此，我们和其他几个研究小组最近通过使用光笼合或光开关方法开发了光控PROTACs，作为第三代可控PROTACs的代表。在这篇综述中，我们总结了新兴的光控PROTACs以及实现PROTACs时空控制的其他潜在方法的前景。
