Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
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Munchhof MJ, Li Q, Shavnya A, Borzillo GV, Boyden TL, Jones CS, LaGreca SD, Martinez-Alsina L, Patel N, Pelletier K, Reiter LA, Robbins MD, Tkalcevic GT
Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
ACS Med Chem Lett. 2011 Dec 21;3(2):106-11. doi: 10.1021/ml2002423. eCollection 2012 Feb 9.
- PubMed ID
- 24900436 [ View in PubMed]
- Abstract
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 1 that resulted in the identification of Smoothened inhibitor 1-((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.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Glasdegib Smoothened homolog Protein Humans YesInhibitorDetails