MEK inhibitors: The chemistry and biological activity of U0126, its analogs, and cyclization products

Autor: Santella Joseph B, John Wityak, Ruth R. Wexler, Robert A. Copeland, Pitts William J, Deborah A. Stradley, Frank W. Hobbs, Peggy Scherle, Elizabeth J. Manos, A. Christine Tabaka, Jung-Hui Sun, Kurumi Y. Horiuchi, James M. Trzaskos, William Eric Frietze, Ronald L. Magolda, Duncia John, Andrea J. Daulerio, Richard E. Olson, C. Anne Higley, Christopher A. Teleha, Richard A. Earl, F.Wayne Rankin, Margaret F. Favata, Karl F. Blom, George L. Trainor
Rok vydání: 1998
Předmět:
Zdroj: Bioorganic & Medicinal Chemistry Letters. 8:2839-2844
ISSN: 0960-894X
DOI: 10.1016/s0960-894x(98)00522-8
Popis: 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 microM for MEK 1 and 0.06 microM 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.
Databáze: OpenAIRE