PF-5274857

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Chemical Structure| 1373615-35-0 同义名 : -
CAS号 : 1373615-35-0
货号 : A427005
分子式 : C20H25ClN4O3S
纯度 : 98%
分子量 : 436.955
MDL号 : MFCD22420827
存储条件：

Pure form Sealed in dry, store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(274.63 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Smoothened (Smo) is a G-protein-coupled receptor that plays a pivotal role within the Hedgehog (HH) signaling pathway, which links to the formation of basal cell carcinoma, medulloblastoma, and other cancers. PF-5274857 is a highly selective SMO antagonist with IC50 values of 5.8 nM. In vitro, PF-5274857 specifically bound to Smo with Ki value of 4.6 nM. In addition, PF-5274857 completely inhibited Shh-induced Hh pathway activity with IC50 value of 2.7 nM measured by the transcriptional activity of Smo downstream gene Gli1 in MEF cells. In vivo, Oral administration of PF-5274857 at 1, 5, 10 and 30 mg/kg once daily for 6 days in the Ptch+/- p53+/- medulloblastoma allograft mice model with tumor group inhibition (TGI) of 39%, 80%, 119% and 133%, respectively. The above result suggested that PF-5274857 significant dose-dependent TGI and induced tumor regression at dose more than 10 mg/kg. PF-5274857 inhibited Gli1 mRNA transcription with IC50 values of 8.9 nM in the Ptch+/- p53+/- medulloblastoma allograft mice model. Oral administration of PF-5274857 at 30 mg/kg improved the survival rate in primary Ptch+/- p53-/- medulloblastoma mice. In addition, subcutaneous administration of PF-5274857 at 10 mg/kg showed approximately 40% of unbound PF527857 in the plasma was able to cross the blood-brain barrier in rats within 4 hours postdose[2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.29mL

0.46mL

0.23mL

11.44mL

2.29mL

1.14mL

22.89mL

4.58mL

2.29mL
参考文献

[1]Zhou WJ, Chen J, et al. [Inhibition of Cigarettes Smoke-induced Epithelial to Mesenchymal Transition by the SMO Inhibitor PF-5274857 in Beas-2b Epithelial Cells] . Sichuan Da Xue Xue Bao Yi Xue Ban. 2016 Jul;47(4):485-490. Chinese.

[2]Rohner A, Spilker M E, Lam J L, 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. Molecular Cancer Therapeutics, 2012, 11(1): 57-65.