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HPI-1

Hedgehog通路抑制剂

产品号 #(选择产品)

产品号 #72492_C

Hedgehog通路抑制剂

总览

HPI-1 是一种 Hedgehog (HH) 通路抑制剂,可抑制 Sonic HH 信号传导 (IC₅₀ = 1.5 µM),且对 WNT 信号传导 (IC₅₀ ≥ 30 µM) 不产生显著影响 (Hyman 等人)。HPI-1 可抑制由 Fused 抑制因子缺失或 Gli 过表达引起的 HH 激活,提示其作用于 GLI 蛋白的翻译后修饰或 GLI 与辅因子的相互作用(Hyman et al.)。

维持和自我更新
·在培养的小脑颗粒神经元前体细胞中,通过抑制致癌平滑(SMO)突变体SMOM2介导的增殖,证明了Hedgehog通路的重要性(Hyman et al.)。

癌症研究
·抑制 MDA-MB-231 乳腺癌细胞的生长(Kwon et al.)。

细胞类型
癌细胞及细胞系,神经干/祖细胞
 
种属
人,小鼠,非人灵长类,其它细胞系,大鼠
 
应用
培养
 
研究领域
癌症,神经科学
 
化学式
C₂₇H₂₉NO₆ • XH₂O
 
纯度
> 95%
 
通路
Hedgehog
 
靶点
GLI
 

产品说明书及文档

请在《产品说明书》中查找相关支持信息和使用说明,或浏览下方更多实验方案。

Document Type
Product Name
Catalog #
Lot #
Language
Product Name
HPI-1 (Hydrate)
Catalog #
72492
Lot #
All
Language
English
Document Type
Safety Data Sheet
Product Name
HPI-1 (Hydrate)
Catalog #
72492
Lot #
All
Language
English

相关材料与文献

技术资料 (3)

文献 (2)

Gli1 enhances migration and invasion via up-regulation of MMP-11 and promotes metastasis in ERα negative breast cancer cell lines. Kwon Y-J et al. Clinical & experimental metastasis 2011 JUN

Abstract

Gli1 is an established oncogene and its expression in Estrogen Receptor (ER) α negative and triple negative breast cancers is predictive of a poor prognosis; however, the biological functions regulated by Gli1 in breast cancer have not been extensively evaluated. Herein, Gli1 was over-expressed or down-regulated (by RNA interference and by expression of the repressor form of Gli3) in the ERα negative, human breast cancer cell lines MDA-MB-231 and SUM1315. Reduced expression of Gli1 in these two cell lines resulted in a decrease in migration and invasion. Gli1 over-expression increased the migration and invasion of MDA-MB-231 cells with a corresponding increase in expression of MMP-11. Silencing MMP-11 in MDA-MB-231 cells that over-expressed Gli1 abrogated the Gli1-induced enhancement of migration and invasion. Sustained suppression of Gli1 expression decreased growth of MDA-MB-231 in vitro by increasing apoptosis and decreasing proliferation. In addition, silencing of Gli1 reduced the numbers and sizes of pulmonary metastases of MDA-MB-231 in an in vivo experimental metastasis assay. In summary, Gli1 promotes the growth, survival, migration, invasion and metastasis of ERα negative breast cancer. Additionally, MMP-11 is up-regulated by Gli1 and mediates the migration and invasion induced by Gli1 in MDA-MB-231.
Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade. Hyman JM et al. Proceedings of the National Academy of Sciences of the United States of America 2009 AUG

Abstract

Inappropriate activation of the Hedgehog (Hh) signaling pathway has been implicated in a diverse spectrum of cancers, and its pharmacological blockade has emerged as an anti-tumor strategy. While nearly all known Hh pathway antagonists target the transmembrane protein Smoothened (Smo), small molecules that suppress downstream effectors could more comprehensively remediate Hh pathway-dependent tumors. We report here four Hh pathway antagonists that are epistatic to the nucleocytoplasmic regulator Suppressor of Fused [Su(fu)], including two that can inhibit Hh target gene expression induced by overexpression of the Gli transcription factors. Each inhibitor has a unique mechanism of action, and their phenotypes reveal that Gli processing, Gli activation, and primary cilia formation are pharmacologically targetable. We further establish the ability of certain compounds to block the proliferation of cerebellar granule neuron precursors expressing an oncogenic form of Smo, and we demonstrate that Hh pathway inhibitors can have tissue-specific activities. These antagonists therefore constitute a valuable set of chemical tools for interrogating downstream Hh signaling mechanisms and for developing chemotherapies against Hh pathway-related cancers.

更多信息

更多信息
种属 Human, Mouse, Non-Human Primate, Other, Rat
Chemical Formula C₂₇H₂₉NO₆ • XH₂O
纯度 > 95%
Target GLI
Pathway Hedgehog
质量保证:

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