Design, Synthesis, and Biological Evaluation of MEK PROTACs

  • J Med Chem. 2020 Jan 9;63(1):157-162. doi: 10.1021/acs.jmedchem.9b00810.
Stefan Vollmer ,  Danen Cunoosamy ,  Huafei Lv  1 ,  Huanxi Feng  1 ,  Xia Li  1 ,  Ziyang Nan  1 ,  Wenzhen Yang  1 ,  Matthew W D Perry
Affiliations
  • 1. Pharmaron Beijing Company, Limited , No. 6 Taihe Road, BDA , Beijing 100176 , P.R. China.
PMID: 31804822 DOI: 10.1021/acs.jmedchem.9b00810
Abstract

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.

Products