Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 3, Issue 2, Pages 106-111Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ml2002423
Keywords
Smoothened; Hedgehog signaling pathway; PF-04449913
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Inhibitors of the Hedgehog signaling pathway have generated a great deal of interest in the oncology area due to the mounting evidence of their potential to provide promising therapeutic options for patients. Herein, we describe the discovery strategy to overcome the issues inherent in lead structure I that resulted in the identification of Smoothened inhibitor 14(2R,4R)-2-(1H-benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (PF-04449913, 26), which has been advanced to human clinical studies.
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