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PF-5274857
本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。
PF-5274857图片
CAS NO:1373615-35-0
包装与价格：
包装价格(元)
10mM (in 1mL DMSO)电议
5mg电议

产品介绍
PF-5274857 是一种有效的、选择性的、具有口服活性的脑渗透性 Smo 拮抗剂，IC50 为 5.8 nM，Ki 为 4.6 nM。 PF-5274857 具有研究肿瘤类型的潜力，包括由激活的 Hh 通路驱动的脑肿瘤和脑转移。
Cas No.1373615-35-0
化学名1-[4-[5-chloro-4-(3,5-dimethylpyridin-2-yl)pyridin-2-yl]piperazin-1-yl]-3-methylsulfonylpropan-1-one
Canonical SMILESCC1=CC(=C(N=C1)C2=CC(=NC=C2Cl)N3CCN(CC3)C(=O)CCS(=O)(=O)C)C
分子式C20H25ClN4O3S
分子量436.96
溶解度≥ 19.65mg/mL in DMSO
储存条件Store at -20°C
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping ConditionEvaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
产品描述

PF-5274857 is an inhibitor of hedgehog (Hh) signaling pathway and is identified as a potent and selective antagonist of Smoothened (Smo) with an IC50 of 5.8 nM.

Smoothened, a G protein-coupled receptor, is a component of the hedgehog signaling pathway and is conserved from flies to humans. This protein is the molecular target of the teratogen cyclopamine. SMO can act as an oncogene and the activation of SMO mutations leads to unregulated activation of the hedgehog pathway and cancer.

In MEF cells, treatment of PF-5274857 completely blocked Shh-induced Hh pathway activity, which was measured by the transcriptional activity of Smo downstream gene Gli1.

In vivo, PF-5274857 showed anti-tumor activity in a mouse medulloblastoma model with IC50 of 8.9 nM. PF-5274857 also shows significant dose-dependent tumor growth inhibition (TGI) and induces tumor regression. In skin tissue, downregulation of Gli1 and Gli2 is also observed with a similar time course by PF-52748571.

Reference:
1.   Rohner A, Spilker ME, Lam JL, 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.