PF-5274857

- Overview
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    Background
    
    PF-5274857 is an inhibitor of hedgehog (Hh) signaling pathway and is identified as a potent and selective antagonist of Smoothened (Smo) with an IC50 of 5.8 nM.
    Smoothened, a G protein-coupled receptor, is a component of the hedgehog signaling pathway and is conserved from flies to humans. This protein is the molecular target of the teratogen cyclopamine. SMO can act as an oncogene and the activation of SMO mutations leads to unregulated activation of the hedgehog pathway and cancer.
    In MEF cells, treatment of PF-5274857 completely blocked Shh-induced Hh pathway activity, which was measured by the transcriptional activity of Smo downstream gene Gli1.
    In vivo, PF-5274857 showed anti-tumor activity in a mouse medulloblastoma model with IC50 of 8.9 nM. PF-5274857 also shows significant dose-dependent tumor growth inhibition (TGI) and induces tumor regression. In skin tissue, downregulation of Gli1 and Gli2 is also observed with a similar time course by PF-52748571.
- Properties
  - Categories
    
    Smo antagonist, potent and selective
    
    Alternative Name
    
    1-[4-[5-chloro-4-(3,5-dimethylpyridin-2-yl)pyridin-2-yl]piperazin-1-yl]-3-methylsulfonylpropan-1-one
    
    CAS Number
    
    1373615-35-0
    
    Molecular Formula
    
    C20H25ClN4O3S
    
    Molecular Weight
    
    436.96
    
    Appearance
    
    A solid
    
    Purity
    
    98.00%
    
    Solubility
    
    insoluble in EtOH; ≥17.6 mg/mL in H2O with ultrasonic; ≥19.65 mg/mL in DMSO
    
    Storage
    
    Store at -20°C
    
    SMILES
    
    CC1=CC(=C(N=C1)C2=CC(=NC=C2Cl)N3CCN(CC3)C(=O)CCS(=O)(=O)C)C
    
    * For Research Use Only