MEK inhibitors: the chemistry and biological activity of U0126, its analogs, and cyclization products
JV Duncia, JB Santella III, CA Higley, WJ Pitts… - Bioorganic & medicinal …, 1998 - Elsevier
JV Duncia, JB Santella III, CA Higley, WJ Pitts, J Wityak, WE Frietze, FW Rankin, JH Sun…
Bioorganic & medicinal chemistry letters, 1998•ElsevierIn search of antiinflammatory drugs with a new mechanism of action, U0126 was found to
functionally antagonize AP-1 transcriptional activity via noncompetitive inhibition of the dual
specificity kinase MEK with an IC50 of 0.07 μM for MEK 1 and 0.06 μM for MEK 2. U0126
can undergo isomerization and cyclization reactions to form a variety of products, both
chemically and in vivo, all of which exhibit less affinity for MEK and lower inhibition of AP-1
activity than parent, U0126.
functionally antagonize AP-1 transcriptional activity via noncompetitive inhibition of the dual
specificity kinase MEK with an IC50 of 0.07 μM for MEK 1 and 0.06 μM for MEK 2. U0126
can undergo isomerization and cyclization reactions to form a variety of products, both
chemically and in vivo, all of which exhibit less affinity for MEK and lower inhibition of AP-1
activity than parent, U0126.
In search of antiinflammatory drugs with a new mechanism of action, U0126 was found to functionally antagonize AP-1 transcriptional activity via noncompetitive inhibition of the dual specificity kinase MEK with an IC50 of 0.07 μM for MEK 1 and 0.06 μM for MEK 2. U0126 can undergo isomerization and cyclization reactions to form a variety of products, both chemically and in vivo, all of which exhibit less affinity for MEK and lower inhibition of AP-1 activity than parent, U0126.
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