PF-5274857CAS号: 1373615-35-0分子式: C20H25ClN4O3S分子量: 436.96描述纯度储存/保存方法别名可溶性/溶解性靶点In vitro(体外研究)In vivo(体内研究)参考文献
产品描述 | |
描述 |
PF-5274857的Ki为4.6 nM. PF-5274857可以完全抑制 Shh诱导的Hh通路活性,通过在MEF细胞中测量Smo下游基因 Gli1 的转录活性可知IC50为2.7nM。PF-5274857可以结合 Smo,IC50 为 5.8 nM. PF-5274857对μ-阿片受体可以微弱抑制,在随后的一项功能分析中测得解离常数为36μM |
纯度 |
>98%
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储存/保存方法 |
Store at -20℃ for one year(Powder);Store at 2-4℃ for two weeks;Store at -20℃ for six months after dissolution.
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基本信息 | |
别名 |
PF5274857;PF 5274857
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可溶性/溶解性 |
DMSO :93 mg/mL (212.83 mM)
Water :93 mg/mL (212.83 mM) |
生物活性 | |
靶点 |
Smoothened,Smoothened
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In vitro(体外研究) |
PF-5274857 completely inhibits Shh-induced Hh pathway activity with IC50 of 2.7 nM measured by the transcriptional activity of Smo downstream gene Gli1 in MEF cells. The μ-opioid receptor is weakly inhibited by PF-5274857 with a dissociation constant of 36 μM subsequently determined in a functional assay.
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In vivo(体内研究) |
PF-5274857 shows significant dose-dependent tumor growth inhibition (TGI) and induces tumor regression at high doses(>10 mg/kg)., PF-5274857 downregulates Gli1, Gli2, Ptch1, and Ptch2 gene expression levels to various degrees with maximal effects being achieved between 6 and 12 hours post-dose (Gli1 is the most sensitive gene), whereas PF-5274857 has little effect on Smo levels. In skin tissue, downregulation of Gli1 and Gli2 is also observed with a similar time course by PF-5274857. The model-derived drug concentration for half maximal inhibition of the tumor Gli1 mRNA production rate (IC50) by PF-5274857 is determined to be 8.9 nM in the Ptch+/−p53+/− medulloblastoma allograft mice, which mathematically corresponds to tumor regression of 119% TGI after 6 days of plasma exposure at this concentration. In the Ptch+/−p53−/− medulloblastoma allograft mice, the IC50 value is estimated to be 3.5 nM, consistent with the Ptch+/−p53+/− results. PF-5274857 is also able to cross the blood–brain barrier in rats within 4 hours post-dose.
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参考文献 | |
参考文献 |
Effective targeting of Hedgehog signaling in a medulloblastoma model with PF-5274857, a potent and selective Smoothened antagonist that penetrates the blood-brain barrier.
Rohner A,et al. Mol Cancer Ther. 2012 Jan;11(1):57-65. PMID: 分子结构图
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