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环巴胺(Cyclopamine)

Hedgehog 通路抑制剂;抑制 Smoothened (SMO)

产品号 #(选择产品)

产品号 #72072_C

Hedgehog 通路抑制剂;抑制 Smoothened (SMO)

总览

环巴胺是一种类固醇生物碱,可在Hedgehog通路激活剂Smoothened的作用位点抑制该通路。环巴胺与G蛋白偶联受体Smoothened的七螺旋束结合,并阻止其向下游信号传导 (Chen et al.)。

维持
·降低大鼠神经祖细胞和小鼠神经球的增殖 (Lai et al.; Palma and Ruiz i Altaba)。
·降低小鼠乳球的增殖 (Liu et al.)。

分化
·促进人胚胎干细胞向胰腺细胞分化 (D'Amour et al.)。

癌症研究
·抑制人和小鼠髓母细胞瘤细胞以及人胶质母细胞瘤细胞的生长 (Bar et al.; Berman et al.)。

别名
11-Deoxojervine,Jervine
 
细胞类型
癌细胞及细胞系,内胚层,PSC衍生,乳腺细胞,神经干/祖细胞,胰腺细胞,多能干细胞
 
种属
人,小鼠,非人灵长类,其它细胞系,大鼠
 
应用
分化
 
研究领域
癌症,神经科学,干细胞生物学
 
CAS 编号
4449-51-8
 
化学式
C₂₇H₄₁NO₂
 
分子量
411.6 克/摩尔
 
纯度
≥ 95 %
 
通路
Hedgehog
 
靶点
SMO
 

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
Cyclopamine
Catalog #
72074, 72072
Lot #
All
Language
English
Document Type
Safety Data Sheet
Product Name
Cyclopamine
Catalog #
72074, 72072
Lot #
All
Language
English

应用领域

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相关材料与文献

技术资料 (4)

文献 (3)

A Novel IL6 Antibody Sensitizes Multiple Tumor Types to Chemotherapy Including Trastuzumab-Resistant Tumors. Zhong H et al. Cancer research 2016 JAN

Abstract

Elevated levels of the proinflammatory cytokine IL6 are associated with poor survival outcomes in many cancers. Antibodies targeting IL6 and its receptor have been developed for chronic inflammatory disease, but they have not yet been shown to clearly benefit cancer patients, possibly due to antibody potency or the settings in which they have been tested. In this study, we describe the development of a novel high-affinity anti-IL6 antibody, MEDI5117, which features an extended half-life and potent inhibitory effects on IL6 biologic activity. MEDI5117 inhibited IL6-mediated activation of STAT3, suppressing the growth of several tumor types driven by IL6 autocrine signaling. In the same models, MEDI5117 displayed superior preclinical activity relative to a previously developed anti-IL6 antibody. Consistent with roles for IL6 in promoting tumor angiogenesis, we found that MEDI5117 inhibited the growth of endothelial cells, which can produce IL6 and support tumorigenesis. Notably, in tumor xenograft assays in mice, we documented the ability of MEDI5117 to enhance the antitumor activities of chemotherapy or gefitinib in combination treatment regimens. MEDI5117 also displayed robust activity on its own against trastuzumab-resistant HER2(+) tumor cells by targeting the CD44(+)CD24(-) cancer stem cell population. Collectively, our findings extend the evidence of important pleiotropic roles of IL6 in tumorigenesis and drug resistance, and offer a preclinical proof of concept for the use of IL6 antibodies in combination regimens to heighten therapeutic responses and overcome drug resistance.
Cyclopamine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma. Bar EE et al. Stem cells (Dayton, Ohio) 2007 OCT

Abstract

Brain tumors can arise following deregulation of signaling pathways normally activated during brain development and may derive from neural stem cells. Given the requirement for Hedgehog in non-neoplastic stem cells, we investigated whether Hedgehog blockade could target the stem-like population in glioblastoma multiforme (GBM). We found that Gli1, a key Hedgehog pathway target, was highly expressed in 5 of 19 primary GBM and in 4 of 7 GBM cell lines. Shh ligand was expressed in some primary tumors, and in GBM-derived neurospheres, suggesting a potential mechanism for pathway activation. Hedgehog pathway blockade by cyclopamine caused a 40%-60% reduction in growth of adherent glioma lines highly expressing Gli1 but not in those lacking evidence of pathway activity. When GBM-derived neurospheres were treated with cyclopamine and then dissociated and seeded in media lacking the inhibitor, no new neurospheres formed, suggesting that the clonogenic cancer stem cells had been depleted. Consistent with this hypothesis, the stem-like fraction in gliomas marked by both aldehyde dehydrogenase activity and Hoechst dye excretion (side population) was significantly reduced or eliminated by cyclopamine. In contrast, we found that radiation treatment of our GBM neurospheres increased the percentage of these stem-like cells, suggesting that this standard therapy preferentially targets better-differentiated neoplastic cells. Most importantly, viable GBM cells injected intracranially following Hedgehog blockade were no longer able to form tumors in athymic mice, indicating that a cancer stem cell population critical for ongoing growth had been removed. Disclosure of potential conflicts of interest is found at the end of this article.
Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. D'Amour KA et al. Nature biotechnology 2006 NOV

Abstract

Of paramount importance for the development of cell therapies to treat diabetes is the production of sufficient numbers of pancreatic endocrine cells that function similarly to primary islets. We have developed a differentiation process that converts human embryonic stem (hES) cells to endocrine cells capable of synthesizing the pancreatic hormones insulin, glucagon, somatostatin, pancreatic polypeptide and ghrelin. This process mimics in vivo pancreatic organogenesis by directing cells through stages resembling definitive endoderm, gut-tube endoderm, pancreatic endoderm and endocrine precursor--en route to cells that express endocrine hormones. The hES cell-derived insulin-expressing cells have an insulin content approaching that of adult islets. Similar to fetal beta-cells, they release C-peptide in response to multiple secretory stimuli, but only minimally to glucose. Production of these hES cell-derived endocrine cells may represent a critical step in the development of a renewable source of cells for diabetes cell therapy.

更多信息

更多信息
Molecular Weight 411.6 g/mol
种属 Human, Mouse, Non-Human Primate, Other, Rat
Alternative Names 11-Deoxojervine, Jervine
Cas Number 4449-51-8
Chemical Formula C₂₇H₄₁NO₂
纯度 ≥ 95%
Target SMO
Pathway Hedgehog
质量保证:

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