Proteolysis-targeting chimera (PROTAC) delivery system: advancing protein degraders towards clinical translation.
Proteolysis-targeting chimera (PROTAC) delivery system: advancing protein degraders towards clinical translation.
复制标题
DOI：
10.1039/d1cs00762a
复制
发表时间：
2022-07-04
影响因子：
46.2
通讯作者：
中科院分区：
文献类型：
--
作者：
针对嵌合体的蛋白分解(PROTACs)是一种新兴的治疗实体，旨在通过劫持泛素-蛋白酶体系统来降解靶蛋白，具有彻底改变医疗保健行业的潜力。这种蛋白质降解策略的广泛适用性已经通过几个E3连接酶和通过构建模块化嵌合结构的各种不同的靶点得到了验证。尽管最近努力促进将PROTAC用于临床应用，但大多数PROTAC并未超过药物开发的临床前阶段。有几个原因阻碍了PROTAC进入市场，而向目标地点交付的不足是最具挑战性的障碍之一。随着对加速翻译过程的需求的增加，将PROTACs和递送系统的概念结合起来以提高PROTACs的体内性能已经被探索。这些改进的给药策略可以消除PROTAC的不良物理化学性质，提高其靶向性，并减少其非靶向副作用。强大的PROTAC和多功能递送系统的集成将为靶向蛋白质降解领域开辟一个新兴的方向。在这篇综述中，我们将综述通过递送策略提高PROTAC体内降解效率的最新进展，概述基于PROTAC的递送系统的设计原则，讨论PROTAC目前面临的挑战，并展望该领域的未来机遇。这篇教程综述讨论了药物输送系统和PROTAC的融合，调查了新兴的PROTAC输送策略，总结了它们的设计原则，阐明了它们的挑战，并展望了未来的翻译机会。
Proteolysis Targeting Chimeras (PROTACs), an emerging therapeutic entity designed to degrade target proteins by hijacking the ubiquitin-proteasome system, have the potential to revolutionize the healthcare industry. The broad applicability of this protein degradation strategy has been verified with a few E3 ligases and a variety of distinct targets through the construction of modular chimeric structures. Despite recent efforts to promote the use of PROTACs for clinical applications, most PROTACs do not make it beyond the preclinical stage of drug development. There are several reasons that prevent PROTACs from reaching the market, and the inadequate delivery to the target site is one of the most challenging hurdles. With the increasing need for accelerating the translational process, combining the concepts of PROTACs and delivery systems has been explored to enhance the in vivo performance of PROTACs. These improved delivery strategies can eliminate unfavorable physicochemical properties of PROTACs, improve their targetability, and decrease their off-target side effects. The integration of powerful PROTACs and versatile delivery systems will inaugurate a burgeoning orientation for the field of targeted protein degradation. In this review, we will survey the latest progress in improving the in vivo degradation efficacy of PROTACs through delivery strategies, outline design principles for PROTAC-based delivery systems, discuss the current challenges with PROTACs, and outlook future opportunities in this field. This tutorial review discusses the convergence of drug delivery systems and PROTACs, surveys the burgeoning PROTAC delivery strategies, summarizes their design principles, clarifies their challenges, and outlooks future translational opportunities.
登录
查看更多内容
影响因子：
46.2
作者：
Karimi M;Ghasemi A;Sahandi Zangabad P;Rahighi R;Moosavi Basri SM;Mirshekari H;Amiri M;Shafaei Pishabad Z;Aslani A;Bozorgomid M;Ghosh D;Beyzavi A;Vaseghi A;Aref AR;Haghani L;Bahrami S;Hamblin MR
通讯作者：
Hamblin MR
BET-Protacs的受控递送：在乳腺癌中对MZ1负载的聚合物抗体共轭纳米颗粒的体外评估。
影响因子：
5.4
作者：
Cimas FJ;Niza E;Juan A;Noblejas-López MDM;Bravo I;Lara-Sanchez A;Alonso-Moreno C;Ocaña A
通讯作者：
Ocaña A
发现口服活性 VHL 募集 PROTAC，可在体内实现强劲的 HMGCR 降解和有效的降血脂活性
DOI：
10.1016/j.apsb.2020.11.001
发表时间：
2021-05
期刊：
Acta pharmaceutica Sinica. B
影响因子：
--
作者：
Luo G;Li Z;Lin X;Li X;Chen Y;Xi K;Xiao M;Wei H;Zhu L;Xiang H
通讯作者：
Xiang H
影响因子：
64.8
作者：
Banik SM;Pedram K;Wisnovsky S;Ahn G;Riley NM;Bertozzi CR
通讯作者：
Bertozzi CR
DOI：
10.1038/s41568-021-00365-x
发表时间：
2021-10
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Dale B;Cheng M;Park KS;Kaniskan HÜ;Xiong Y;Jin J
通讯作者：
Jin J