嵌合小分子、PROTAC和SNIPER介导的靶向蛋白质降解
Targeted Protein Degradation by Chimeric Small Molecules, PROTACs and SNIPERs.
作者信息
Naito Mikihiko, Ohoka Nobumichi, Shibata Norihito, Tsukumo Yoshinori
机构信息
Laboratory Molecular Target and Gene Therapy Products, National Institute of Health Sciences, Kawasaki, Japan.
出版信息
Front Chem. 2019 Dec 10;7:849. doi: 10.3389/fchem.2019.00849. eCollection 2019.
Technologies that induce targeted protein degradation by small molecules have been developed recently. Chimeric small molecules such as Proteolysis Targeting Chimeras (PROTACs) and Specific and Non-genetic IAP-dependent Protein Erasers (SNIPERs), and E3 modulators such as thalidomides, hijack the cellular machinery for ubiquitylation, and the ubiquitylated proteins are subjected to proteasomal degradation. This has motivated drug development in industry and academia because "undruggable targets" can now be degraded by targeted protein degradation.
近年来，已开发出通过小分子诱导靶向蛋白质降解的技术。嵌合小分子，如蛋白酶靶向嵌合体（PROTACs）和特异性非基因IAP依赖性蛋白清除剂（SNIPERs），以及沙利度胺等E3调节剂，利用细胞泛素化机制，使泛素化的蛋白质遭受蛋白酶体降解。这推动了工业界和学术界的药物开发，因为“不可成药靶点”现在可以通过靶向蛋白质降解来降解。
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