PF-5274857 free base · Synonyms: PF 5274857 · PF5274857

PF-5274857 is a potent, selective, orally active and brain-penetrant antagonist of Smo.

For research use only. Not for human or veterinary use.

Target Smo

Research area Cancer

Purity >98% Stock Inquire

Data Sheet SDS COA

PF-5274857 structure

CAS No.: 1373615-35-0

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
500 mg	USD 450.00	BP-02143-500mg	In stock	Get quote
1 g	USD 720.00	BP-02143-1g	In stock	Get quote
2 g	USD 1,120.00	BP-02143-2g	In stock	Get quote
3 g	USD 1,350.00	BP-02143-3g	In stock	Get quote
5 g	USD 2,800.00	BP-02143-5g	In stock	Get quote

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Description

PF-5274857 is a potent, selective, orally active and brain-penetrant antagonist of Smo, with an IC50 of 5.8 nM and Ki of 4.6 nM. PF-5274857 has potential for research of tumor types including brain tumors and brain metastasis driven by an activated Hh pathway .

Biological activity

In Vitro PF-5274857 completely inhibits Shh-induced Hh pathway activity with an IC50 of 2.7±1.4 nM measured by the transcriptional activity of Smo downstream gene Gli1 in MEF cells. PF-5274857 shows less than 20% inhibition against a broad panel of protein kinases at 1 μM. In Vivo PF-5274857 (1-30 mg/kg; p.o. once daily for 6 days) shows robust antitumor efficacy and correlation between PK and PD in medulloblastoma allograft mice models. PF-5274857 (10 mg/kg; i.h.) in the plasma is able to cross the blood-brain barrier in rats within 4 hours postdose. PF-5274857 (10-100 mg/kg; p.o. once daily for 4 days) is able to target Smo in the brain leading to the downregulation of Hh pathway activity in the brain tumor. PF-5274857 (30 mg/kg; p.o. once daily for 34 days) increases the survival rates of primary Ptch+/? p53?/? medulloblastoma mice. PF-5274857 (5-30 mg/kg; p.o.) exhibits the apparent volume of distribution of 5.6±0.5 L/kg and the half-life (T1/2) of 1.7±0.1 hours.

Identifiers

SMILES: CC1=CN=C(C(C)=C1)C1=CC(=NC=C1Cl)N1CCN(CC1)C(=O)CCS(C)(=O)=O
InChIKey: BBVNTTZIOTWDSV-UHFFFAOYSA-N

Specifications

MW (average): 436.9560
Formula: C₂₀H₂₅ClN₄O₃S
CAS No.: 1373615-35-0
Physical state: Solid
Color: Light yellow to yellow
Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage: Powder -20℃ 3 years; 4℃ 2 years; In solvent -20℃ 1 year;

Solubility

Soluble in DMSO/H2O

Documents

References

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

Same research area

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