Cyclopamine
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Cyclopamine是一种天然存在的、特异性的甾体生物碱类Hedgehog (Hh)信号小分子抑制剂。在人乳腺癌细胞中,cyclopamine有效抑制肿瘤生长,具有显著的抗侵袭、抗增殖和抗雌激素效力[1][2]。在FXR-bla(法尼醇X受体-β-内酰胺酶)实验中,cyclopamine的EC50值为10.57 μM[3]。
Hh信号通路在胚胎发育和肿瘤发生中起关键作用[4]。Hh信号通路在人体各种组织中调控细胞增殖和分化,它与许多人体恶性肿瘤中异常的细胞存活相关,从BCCs和髓母细胞瘤到小细胞肺癌、胃肠癌、乳腺癌和前列腺癌[1]。
在MCF-7细胞和MDA-MB-231细胞中,用cyclopamine(10或20 μM)处理,并孵育0-10天,与对照细胞相比,在第3天和第6天,cyclopamine显著减少细胞的增殖率(P<0.01)。在MCF-7细胞中,cyclopamine显著诱导G1期细胞周期停滞(P<0.01),适度减少S期细胞百分比,从22%减少到16%(P<0.01)。在MDA-MB-231细胞中,cyclopamine显著增加G1期细胞数量。与对照相比,cyclopamine处理的MCF-7和MDA-MB-231细胞的侵袭率明显下降[2]。
用cyclopamine处理胚胎后导致明显的外部缺陷,包括独眼、长鼻、小眼球、胸部前凸、缺肢和体型减小。胃肠器官检查显示严重缺陷,包括更短的肠管长度和前肠源性器官中间充质细胞的数量。在十二指肠、胃和背侧胰腺中均发现异位结构[5]。
参考文献:
[1]. Marc J. Meth and Jeffrey M. Weinberg. Cyclopamine: Inhibiting Hedgehog in the Treatment of Psoriasis. Continuing Medical Education, 2006, 78: 185-188.
[2]. Jun Che, Fu-Zheng Zhang, Chao-Qian Zhao, et al. Cyclopamine is a novel Hedgehog signaling inhibitor with significant anti?proliferative, anti?invasive and anti?estrogenic potency in human breast cancer cells. Oncology Letters, 2013, 5: 1417-1421.
[3]. Chia-Wen Hsu, Jinghua Zhao, Ruili Huang, et al. Quantitative High-Throughput Profiling of Environmental Chemicals and Drugs that Modulate Farnesoid X Receptor. Scientific Reports, 2014, 4: 6437.
[4]. Robert J. Lipinski, Paul R. Hutson, Paul W. Hannam, et al. Dose- and Route-Dependent Teratogenicity, Toxicity, and Pharmacokinetic Profiles of the Hedgehog Signaling Antagonist Cyclopamine in the Mouse. Toxicological Sciences, 2008, 104(1):189-197.
[5]. Seung K. Kim and Douglas A. Melton. Pancreas development is promoted by cyclopamine, a Hedgehog signaling inhibitor. Proc. Natl. Acad. Sci. USA, 1998, 95: 13036-13041.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 411.62 |
Cas No. | 4449-51-8 |
Formula | C27H41NO2 |
Synonyms | 11-Deoxojervine |
Solubility | insoluble in EtOH; insoluble in H2O; ≥6.86 mg/mL in DMSO |
Chemical Name | (3S,3'R,3'aS,6'S,6aS,6bS,7'aR,9R,11aS,11bR)-3',6',10,11b-tetramethylspiro[2,3,4,6,6a,6b,7,8,11,11a-decahydro-1H-benzo[a]fluorene-9,2'-3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine]-3-ol |
SDF | Download SDF |
Canonical SMILES | CC1CC2C(C(C3(O2)CCC4C5CC=C6CC(CCC6(C5CC4=C3C)C)O)C)NC1 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验: [1] | |
细胞系 |
AA/C1、RG/C2、CaCo2、HT29和SW480细胞 |
制备方法 |
该化合物在DMSO中的溶解度小于10 mM,若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。 |
反应条件 |
细胞产量抑制:20 μM,48小时;凋亡诱导:10 μM,48小时(通过PARP表达测量) |
实验结果 |
在所测试的所有人结肠直肠肿瘤细胞系中,Cyclopamine以剂量依赖性方式显著降低细胞产量。Cyclopamine还显著诱导每种细胞系的凋亡。CaCo2细胞系对环巴胺诱导的细胞凋亡特别敏感。 |
动物实验: [2] | |
动物模型 |
C57BL/6J小鼠 |
给药剂量 |
腹腔注射,160 mg/kg/day,持续31小时。 |
实验结果 |
在测试动物中,Cyclopamine显示致畸潜力。受影响的胚胎略小于正常同窝出生,并表现出轻微的口鼻钝化以及唇裂和腭裂。胚胎表现出单侧和双侧完全裂口,裂口延伸到原发和继发上腭。面部裂缝通常伴有开放的眼睑缺陷,在其中一个胚胎中存在前肢联合。 |
注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。 |
References: [1] Qualtrough D, Buda A, Gaffield W, et al. Hedgehog signalling in colorectal tumour cells: induction of apoptosis with cyclopamine treatment. International journal of cancer, 2004, 110(6): 831-837. [2] Lipinski R J, Hutson P R, Hannam P W, et al. Dose-and route-dependent teratogenicity, toxicity, and pharmacokinetic profiles of the hedgehog signaling antagonist cyclopamine in the mouse. Toxicological sciences, 2008, 104(1): 189-197. |
Description | Purmorphamine is a blocker of BODIPY-cyclopamine binding to Smo with IC50 of ~ 1.5 μM and also is an inducer of osteoblast differentiation with EC50 of 1 μM. | |||||
Targets | Smoothened (Smo) | |||||
IC50 | 46 nM |
质量控制和MSDS
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