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Description: Glasdegib (formerly known as PF-04449913; PF4449913; PF04449913; PF-4449913) is a novel, potent, and orally bioavailable small-molecule inhibitor of Smoothened (Smo) in the Hedgehog (Hh) signaling pathway with potential antitumor activity. It inhibits Smoothened (Smo) with an IC50 of 5 nM. The Hh signaling pathway plays an important role in cellular growth, differentiation and repair. Constitutive activation of Hh pathway signaling has been observed in various types of cancers. Glasdegib significantly reduces medulloblastoma growth in a Ptch1+/-p53+/- allograft model at doses that decreased murine Shh target gene expression. In stromal co-culture experiments, FACS analysis demonstrates a significant reduction in BC LSC by PF-04449913 when compared with normal progenitors.
References: ACS Med Chem Lett. 2011 Dec 21;3(2):106-11.
Related CAS#: 2030410-25-2 (Maleate); 1095173-27-5 (free base); 1095173-64-0 (HCl); 1352568-48-9 (2HCl)
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
In vitro activity: In vitro microsomal assays, PF-04449913 have high clearance in rat and low clearance in dog and human, without inhibiting any of the major cytochrome P450 isoforms.
Kinase Assay: Glasdegib (formerly known as PF-04449913) is a novel potent, and orally bioavailable small-molecule inhibitor of Smoothened (Smo) in the Hedgehog (Hh) signaling pathway with IC50 of 5 nM. The Hh signaling pathway plays an important role in cellular growth, differentiation and repair. Constitutive activation of Hh pathway signaling has been observed in various types of cancers. Glasdegib significantly reduces medulloblastoma growth in a Ptch1+/-p53+/- allograft model at doses that decreased murine Shh target gene expression. In stromal co-culture experiments, FACS analysis demonstrates a significant reduction in BC LSC by PF-04449913 when compared with normal progenitors.
Cell Assay: In the Hedgehog (Hh) signaling pathway, the combination of Hh ligands and their receptor Patched leads to the activation of smoothened and subsequently activation of three transcription factors Gli1, Gli2 and Gli3. It then leads to the proliferation of cells. As an antagonist of smoothened, PF-04449913 is developed for treatment of cancer.
Purity ≥98%
COA
MSDS
Selective shh inhibition reduces lsc burden in stromal co-cultures. J Transl Med. 2015 Mar 21;13:98.
Shh inhibition induces cycling of dormant leukemic progenitors. J Transl Med. 2015 Mar 21;13:98.
PF-04449913 induced cell cycle activation enhances TKI sensitivity. J Transl Med. 2015 Mar 21;13:98.
GLI2 induces cell cycle arrest in leukemic progenitors. J Transl Med. 2015 Mar 21;13:98.
SHH pathway deregulation in chronic myeloid leukemia progression. J Transl Med. 2015 Mar 21;13:98.