Proteolysis targeting chimeras (PROTACs) come of age: entering the third decade of targeted protein degradation.
Proteolysis targeting chimeras (PROTACs) come of age: entering the third decade of targeted protein degradation.
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DOI：
10.1039/d1cb00011j
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发表时间：
2021-03-19
影响因子：
4.1
通讯作者：
Crews CM
中科院分区：
文献类型：
--
作者：
Bond MJ;Crews CM
随着20年前PROTAC的发现，靶向蛋白降解（TPD）已经改变了药物开发的前景。PROTAC已经从细胞不可渗透的肽-小分子嵌合体发展为降解人类致癌蛋白的口服生物可利用的临床候选药物。当我们进入TPD的第三个十年时，发现的步伐只会加快。改进的技术正在开发“不可药物化”蛋白质的配体并招募新的E3连接酶。此外，增强的计算能力将加快主动降能器的识别。在这里，我们将讨论在这些领域取得的进展，以及随着这个令人兴奋的领域的下一个十年的开始，我们可以期待哪些进展。随着20年前PROTAC的发现，靶向蛋白降解（TPD）已经改变了药物开发的前景。
With the discovery of PROteolysis TArgeting Chimeras (PROTACs) twenty years ago, targeted protein degradation (TPD) has changed the landscape of drug development. PROTACs have evolved from cell-impermeable peptide-small molecule chimeras to orally bioavailable clinical candidate drugs that degrade oncogenic proteins in humans. As we move into the third decade of TPD, the pace of discovery will only accelerate. Improved technologies are enabling the development of ligands for “undruggable” proteins and the recruitment of new E3 ligases. Moreover, enhanced computing power will expedite identification of active degraders. Here we discuss the strides made in these areas and what advances we can look forward to as the next decade in this exciting field begins. With the discovery of PROteolysis TArgeting Chimeras (PROTACs) twenty years ago, targeted protein degradation (TPD) has changed the landscape of drug development.
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影响因子：
8.6
作者：
Boike L;Cioffi AG;Majewski FC;Co J;Henning NJ;Jones MD;Liu G;McKenna JM;Tallarico JA;Schirle M;Nomura DK
通讯作者：
Nomura DK
影响因子：
50.3
作者：
Bai, Longchuan;Zhou, Haibin;Wang, Shaomeng
通讯作者：
Wang, Shaomeng
影响因子：
6.7
作者：
Cheng, Binbin;Ren, Yichang;Chen, Jianjun
通讯作者：
Chen, Jianjun
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