The discovery of carboline analogs as potent MAPKAP-K2 inhibitors

…, A Abeywardane, D Andersen, M Emmanuel…

Index: Wu, Jiang-Ping; Wang, Ji; Abeywardane, Asitha; Andersen, Denise; Emmanuel, Michel; Gautschi, Elda; Goldberg, Daniel R.; Kashem, Mohammed A.; Lukas, Susan; Mao, Wang; Martin, Leslie; Morwick, Tina; Moss, Neil; Pargellis, Christopher; Patel, Usha R.; Patnaude, Lori; Peet, Gregory W.; Skow, Donna; Snow, Roger J.; Ward, Yancey; Werneburg, Brian; White, Andre Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 16 p. 4664 - 4669

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Citation Number: 53

Abstract

The discovery of a series of potent, carboline-based MK2 inhibitors is described. These compounds inhibit MK2 with IC50s as low as 10nM, as measured in a DELFIA assay. An X- ray crystal structure reveals that they bind in a region near the p-loop and the hinge region of MK2a.