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PF-5274857

Cat. No. M2447
PF-5274857 Structure
Size Price Availability Quantity
5mg USD 220 In stock
10mg USD 370 In stock
25mg USD 500 In stock
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Quality Control
  • Current batch:
  • Purity >99%
  • COA
  • MSDS
Biological Activity

PF-5274857 is a novel Smo antagonist that specifically binds to Smo with a K(i) of 4.6 ± 1.1 nmol/L and completely blocks the transcriptional activity of the downstream gene Gli1 with an IC(50) of 2.7 ± 1.4 nmol/L in cells. The μ-opioid receptor is weakly inhibited by PF-5274857 with a dissociation constant of 36 μM subsequently determined in a functional assay. PF-5274857 was orally available and metabolically stable in vivo. PF-5274857 shows significant dose-dependent tumor growth inhibition (TGI) and induces tumor regression at high doses(>10 mg/kg). PF-5274857 is a potentially attractive clinical candidate for the treatment of tumor types including brain tumors and brain metastasis driven by an activated Hedgehog (Hh) signaling pathway. PF-5274857 is also able to cross the blood–brain barrier in rats within 4 hours post-dose.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 436.96
Formula C20H25ClN4O3S
CAS Number 1373615-35-0
Purity >99%
Solubility DMSO 80 mg/mL
Water 80 mg/mL
Storage at -20°C
References

Effective targeting of Hedgehog signaling in a medulloblastoma model with PF-5274857, a potent and selective Smoothened antagonist that penetrates the blood-brain barrier.
Rohner A, et al. Mol Cancer Ther. 2012 Jan;11(1):57-65. PMID: 22084163.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: PF-5274857 supplier, Hedgehog, inhibitors

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