|1-[4-(5'-氯-3,5-二甲基[2,4'-联吡啶]-2'-基)-1-哌嗪基]-3-(甲基磺酰基)-丙-1-酮|CsnPharm

CAS No.: 1373615-35-0

PF-5274857 Catalog No. CSN15911

Synonyms: PF-5274857

PF-5274857 is a potent and selective Smoothened (Smo) antagonist, inhibits Hedgehog (Hh) signaling with IC50 and Ki of 5.8 nM and 4.6 nM, respectively, and can penetrate the blood–brain barrier.

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400-920-2911

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实验方案

技术信息

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].
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.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.2886 mL
- 11.4428 mL
- 22.8856 mL
- 5 mM
- 0.4577 mL
- 2.2886 mL
- 4.5771 mL
- 10 mM
- 0.2289 mL
- 1.1443 mL
- 2.2886 mL

技术信息

CAS号

1373615-35-0

储存条件

粉末: Sealed in dry,Store in freezer, under -20°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C20H25ClN4O3S

运输

蓝冰

分子量

436.96

别名

PF-5274857

溶解度

DMSO	92.0 mg/mL (210.5 mM)
Ethanol	Insoluble

动物实验配方

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