| Autor: |
Kim Malesky, Victoria Dinkel, Bruno Alicke, Hillary L. Sturgis, Simon Mathieu, Ignacio Aliagas, Sumeet Rana, Kyung Song, Brandon S. Willis, Bonnie Liu, Nikole Randolph, Yingqing Ran, Scott Savage, Wendy B. Young, Edna F. Choo, Ellen R. Laird, Steve Wenglowsky, Stephen E. Gould, Bainian Feng, Michael Shrag, Joachim Rudolph, Li Ren, Kateri A. Ahrendt, Nicholas J. Raddatz, Walter C. Voegtli, Tyler Risom, LeAnn T. Selby, Jonas Grina, Zhaoyang Wen, Susan L. Gloor, Janet Gunzner-Toste, Wen-I Wu, Alexandre J. Buckmelter, Brad Newhouse, Richard Woessner, Stefan Gross, Joshua D. Hansen, Georgia Hatzivassiliou |
| Rok vydání: |
2010 |
| Předmět: |
|
| Zdroj: |
ACS medicinal chemistry letters. 2(5) |
| ISSN: |
1948-5875 |
| Popis: |
The V600E mutation of B-Raf kinase results in constitutive activation of the MAPK signaling pathway and is present in approximately 7% of all cancers. Using structure-based design, a novel series of pyrazolopyridine inhibitors of B-Raf(V600E) was developed. Optimization led to the identification of 3-methoxy pyrazolopyridines 17 and 19, potent, selective, and orally bioavailable agents that inhibited tumor growth in a mouse xenograft model driven by B-Raf(V600E) with no effect on body weight. On the basis of their in vivo efficacy and preliminary safety profiles, 17 and 19 were selected for further preclinical evaluation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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