Accueil>>Signaling Pathways>> Proteases>> Endogenous Metabolite>>Cyclopamine

Cyclopamine (Synonyms: 11-Deoxojervine)

Catalog No.GC13441

La cyclopamine est un antagoniste de la voie Hedgehog (Hh) avec une CI50 de 46 nM dans le test des cellules Hh. La cyclopamine est également un inhibiteur sélectif de Smo.

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Cyclopamine Chemical Structure

Cas No.: 4449-51-8

Taille Prix Stock Qté
10mM (in 1mL DMSO)
38,00 $US
En stock
5mg
38,00 $US
En stock
10mg
44,00 $US
En stock
25mg
73,00 $US
En stock
500mg
1 112,00 $US
En stock
1g
1 998,00 $US
En stock

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Sample solution is provided at 25 µL, 10mM.

Product has been cited by 1 publications

Product Documents

Quality Control & SDS

View current batch:

Protocol

Cell experiment: [1]

Cell lines

AA/C1, RG/C2, CaCo2, HT29 and SW480 cells

Preparation method

The solubility of this compound in DMSO is <10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reaction Conditions

20 μM, 48 hours for cell yield inhibition 10 μM, 48 hours for apoptosis induction (measured by PARP expression)

Applications

Treatment of cyclopamine significantly reduced cell yield in all the tested human colorectal tumour cell lines with a dose-dependent manner. Cyclopamine also remarkably induced apoptosis in each of the cell lines. The CaCo2 cell line showed particular sensitivity to cyclopamine-induced apoptosis.

Animal experiment: [2]

Animal models

C57BL/6J mice

Dosage form

Intraperitoneal injection, 160 mg/kg/day for 31 hours.

Applications

Cyclopamine showed teratogenic potential in the tested animals. Affected embryos were slightly smaller than normal littermates and exhibited mild blunting of the snout as well as cleft lip and palate. Embryos exhibited unilateral and bilateral complete cleft lip with clefts extending into the primary and secondary palate. Facial clefts were often accompanied by open eyelid defects and in one embryo by forelimb syndactyly.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

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.

Background

Cyclopamine is a naturally occurring Hedgehog (Hh)?specific small?molecule signaling steroidal alkaloid inhibitor, causes a profound inhibition of tumor growth, has significant anti?invasive, anti?proliferative and anti?estrogenic potency in human breast cancer cells [2] [1]. The EC50 of cyclopamine is 10.57 μM, it was identified by an FXR-bla (farnesoid X receptor- b-lactamase) assay [3].

Hh signaling pathway plays a critical role in embryonic development and tumorigenesis [4]. Hh signaling pathway shows saliency in regulating cellular proliferation and differentiation in a wide array of human tissues. It is related to aberrant cell survival in numerous human malignancies, ranging from BCCs and medulloblastomas to small cell lung, gastrointestinal, breast and prostate tumors [1].

Treated with cyclopamine (10 or 20 μM) only and incubated for time periods ranging from 0 to10 days, MCF-7 cells and MDA?MB?231 cells displayed a significant reduction in proliferation rate compared with the control cells on days 3 and 6 (P<0.01). In the MCF?7 cells, cyclopamine significantly induced cell accumulation in the G1 phase (P<0.01) and a modest decrease in the S population percentage, from 22 to 16% (P<0.01). In the MDA?MB?231 cells, cyclopamine caused a significant increase in G1 cells. The invasion rate of cyclopamine?treated MCF?7 and MDA?MB?231cells significantly decreased compared with the CK [2].

Embryoes exposed to cyclopamine resulted in visible external defects, including cyclopia, proboscis formation, microphthalmia, thoracic lordosis, amelia and decreased body size. Examination of gastrointestinal organs revealed severe deficits, including less length of the gut tube and mesenchymal cell numbers in foregut-derived organs. Ectopic structures in duodenum, stomach, and dorsal pancreas were also found [5].

References:
[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.

Chemical Properties

Cas No. 4449-51-8 SDF
Synonymes 11-Deoxojervine
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
Canonical SMILES CC1CC2C(C(C3(O2)CCC4C5CC=C6CC(CCC6(C5CC4=C3C)C)O)C)NC1
Formula C27H41NO2 M.Wt 411.62
Solubility ≥ 6.9mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 2.4294 mL 12.1471 mL 24.2943 mL
5 mM 0.4859 mL 2.4294 mL 4.8589 mL
10 mM 0.2429 mL 1.2147 mL 2.4294 mL
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Average Rating: 5 ★★★★★ (Based on Reviews and 5 reference(s) in Google Scholar.)

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