PROTACs: An Emerging Therapeutic Modality in Precision Medicine.
PROTACs: An Emerging Therapeutic Modality in Precision Medicine.
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DOI：
10.1016/j.chembiol.2020.07.020
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发表时间：
2020-08-20
影响因子：
8.6
通讯作者：
Crews, Craig M.
中科院分区：
文献类型：
--
作者：
Nalawansha, Dhanusha A.;Crews, Craig M.
蛋白质靶向降解（TPD）是化学生物学和药物发现领域的一个新纪元。PROTAC（PROteolysis Targeting Chimera）技术通过选择泛素蛋白酶体系统来降解细胞蛋白。在过去的五年中，许多研究扩大了我们对PROTAC独特作用模式和优势的理解，这反过来又激发了学术界和工业界探索PROTAC作为一种新型治疗策略的兴趣。在这篇综述中，我们首先强调了PROTAC的关键优势，然后讨论蛋白质降解的时空调控。接下来，我们探索目前化学上易处理的E3连接酶，重点是用新型E3连接酶扩展现有的库，以揭示TPD的全部潜力。总的来说，这些研究正在指导PROTAC技术的发展，因为它是精准医疗的一种新模式。Nalawansha等人综述了PROTAC技术的优势和最新进展，重点关注蛋白质降解的时空调控、化学上易处理的E3连接酶以及共价和非共价PROTAC。
Targeted Protein Degradation (TPD) has emerged as an exciting new era in chemical biology and drug discovery. PROteolysis TArgeting Chimera (PROTAC) technology targets cellular proteins for degradation by co-opting the Ubiquitin Proteasome System. Over the last five years, numerous studies have expanded our understanding of the unique mode of action and advantages of PROTACs, which has in turn spurred interest in both academia and industry to explore PROTACs as a novel therapeutic strategy. In this review, we first highlight the key advantages of PROTACs and then discuss the spatiotemporal regulation of protein degradation. Next, we explore current chemically tractable E3 ligases focusing on expanding the existing repertoire with novel E3 ligases to uncover the full potential of TPD. Collectively, these studies are guiding the development of the PROTAC technology as it emerges as a new modality in precision medicine. Nalawansha et al. review the advantages and recent advances of the PROTAC technology focusing on the spatiotemporal regulation of protein degradation, the chemically tractable E3 ligases, as well as covalent and non-covalent PROTACs.
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影响因子：
8.6
作者：
Brand, Matthias;Jiang, Baishan;Winter, Georg E.
通讯作者：
Winter, Georg E.
影响因子：
50.3
作者：
Bai, Longchuan;Zhou, Haibin;Wang, Shaomeng
通讯作者：
Wang, Shaomeng
影响因子：
11.2
作者：
Burslem, George M.;Schultz, Anna Reister;Crews, Craig M.
通讯作者：
Crews, Craig M.
影响因子：
4
作者：
Buckley DL;Raina K;Darricarrere N;Hines J;Gustafson JL;Smith IE;Miah AH;Harling JD;Crews CM
通讯作者：
Crews CM
影响因子：
14.8
作者：
Bondeson DP;Mares A;Smith IE;Ko E;Campos S;Miah AH;Mulholland KE;Routly N;Buckley DL;Gustafson JL;Zinn N;Grandi P;Shimamura S;Bergamini G;Faelth-Savitski M;Bantscheff M;Cox C;Gordon DA;Willard RR;Flanagan JJ;Casillas LN;Votta BJ;den Besten W;Famm K;Kruidenier L;Carter PS;Harling JD;Churcher I;Crews CM
通讯作者：
Crews CM