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.
MeSH terms
-
Cell Line, Tumor
-
Drug Design
-
Humans
-
Interleukin-6 / metabolism
-
MAP Kinase Kinase 1 / metabolism*
-
MAP Kinase Kinase 2 / metabolism*
-
Protein Kinase Inhibitors / chemical synthesis
-
Protein Kinase Inhibitors / pharmacology*
-
Proteolysis / drug effects*
-
Sulfonamides / chemical synthesis
-
Sulfonamides / pharmacology*
-
Von Hippel-Lindau Tumor Suppressor Protein / metabolism
Substances
-
IL6 protein, human
-
Interleukin-6
-
Protein Kinase Inhibitors
-
Sulfonamides
-
Von Hippel-Lindau Tumor Suppressor Protein
-
MAP2K2 protein, human
-
MAP Kinase Kinase 1
-
MAP Kinase Kinase 2
-
MAP2K1 protein, human
-
VHL protein, human