Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.

Article Details

Citation

Copy to clipboard

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

Glasdegib

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Glasdegib	Smoothened homolog	Protein	Humans	Yes	Inhibitor	Details