Design, Synthesis, and Biological Evaluation of MEK PROTACs

被引：39

作者：

Vollmer, Stefan ^{[1
,3
]}

Cunoosamy, Danen ^{[1
,3
]}

Lv, Huafei ^{[4
]}

Feng, Huanxi ^{[4
]}

Li, Xia ^{[4
]}

Nan, Ziyang ^{[4
]}

Yang, Wenzhen ^{[4
]}

Perry, Matthew W. D. ^{[1
,2
,3
]}

机构：

[1] AstraZeneca, BioPharmaceut R&D, Translat Sci & Expt Med, S-43183 Gothenburg, Sweden

[2] AstraZeneca, BioPharmaceut R&D, Med Chem, S-43183 Gothenburg, Sweden

[3] AstraZeneca, BioPharmaceut R&D, Res & Early Dev, RIA, S-43183 Gothenburg, Sweden

[4] Pharmaron Beijing Co Ltd, BDA, 6 Taihe Rd, Beijing 100176, Peoples R China

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2020年 / 63卷 / 01期

关键词：

INDUCED PROTEIN-DEGRADATION; INHIBITORS; RAF;

D O I：

10.1021/acs.jmedchem.9b00810

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

PROteolysis TArgeting Chimeras (PROTACs) targeting the degradation of MEK have been designed based on allosteric MEK inhibitors. Inhibition of the phosphorylation of ERK1/2 was less effective with the PROTACs than a small-molecule inhibitor; the best PROTACs, however, were more effective in inhibiting proliferation of A375 cells than an inhibitor.

引用

页码：157 / 162

页数：6

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