BiochemProbe — Life Science Research Reagents

PF-05274857 hydrochloride salt form · hydrochloride · Parent PF-5274857

PF-5274857 hydrochloride 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-05274857 hydrochloride structure

CAS No.: 1613439-62-5

Download structure (.mol)

Pack sizes & pricing

Size Price SKU Stock
25 mg USD 498.00 BP-02143A-25mg In stock Get quote
50 mg USD 800.00 BP-02143A-50mg In stock Get quote
100 mg USD 1,280.00 BP-02143A-100mg In stock Get quote
250 mg USD 2,550.00 BP-02143A-250mg In stock Get quote
500 mg USD 4,080.00 BP-02143A-500mg In stock Get quote
1 g Inquire BP-02143A-1g In stock Inquire

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Description

PF-5274857 hydrochloride 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 hydrochloride 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
O=C(N1CCN(C2=NC=C(Cl)C(C3=NC=C(C)C=C3C)=C2)CC1)CCS(=O)(C)=O.Cl
InChIKey
GULNFUQAVPTTQV-UHFFFAOYSA-N

Specifications

MW (average)
473.4160
Formula
C20H26Cl2N4O3S
CAS No.
1613439-62-5
Physical state
Solid
Color
Pale 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
Please store the product under the recommended conditions in the Certificate of Analysis.

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 Jan;11(1):57-65.

Same target

Search Smo

Same research area

Search Cancer