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PF-5274857

Cat. No. M2447
PF-5274857 Structure
Size Price Availability Quantity
5mg USD 100  USD100 In stock
10mg USD 140  USD140 In stock
25mg USD 300  USD300 In stock
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Quality Control & Documentation
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.

Chemical Information
Molecular Weight 436.96
Formula C20H25ClN4O3S
CAS Number 1373615-35-0
Solubility (25°C) DMSO 80 mg/mL
Water 80 mg/mL
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
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 Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 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 Compound A of 10 mg/kg.

References

[1] Rohner A, et al. Mol Cancer Ther. Effective targeting of Hedgehog signaling in a medulloblastoma model with PF-5274857, a potent and selective Smoothened antagonist that penetrates the blood-brain barrier.

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Keywords: PF-5274857 supplier, Hedgehog, inhibitors, activators


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