Cyclopamine

Catalog #:

IN0029

IN0029-5mg	USD100.0
IN0029-10mg	USD150.0
IN0029-25mg	USD250.0
IN0029-50mg	USD420.0

Synonyms: Cyclopamine, 11-deoxojervine

IUPAC Name:

(2'R,3S,3'R,3'aS,6'S,6aS,6bS,7'aR,11aS,1 1bR)-1,2,3,3'a,4,4',5',6,6',6a,6b,7,7',7'a,8,11,11a,11b- Octadecahydro-3',6',10,11b-tetramethylspiro[9H-benzo [a]fluorene-9,2'(3'H)-furo[3,2-b]pyridin]-3-ol

Functional Activity:

Cyclopamine is an inhibitor of the hedgehog signaling pathway (HH) via interrupting the balance of the active and inactive forms of the Smoothened protein. This signaling pathway is important in embryonic development and when it goes awry, deformities can occur. However, errant activation of the pathway can also trigger cancer in adult humans.

Cyclopamine is a lipophilic compound extracted from the lily Veratrum californicum. It antagonizes Smo activity by binding to its heptahelical bundle. Thus, it can block pathway activation resulting in any of the two upstream events of Smo, i.e., either from PTCH mutations or from Hh ligand over-expression. Cyclopamine is currently being investigated as a treatment agent in basal cell carcinoma, medulloblastoma, and rhabdomyosarcoma, tumors connected to excessive Hh activity,etc.

In preclinical models of rodent and human prostate cancer, cyclopamine can inhibit tumor growth as well as tumor progression. Administration of cyclopamine causes both down-regulation of proliferation and initiation of apoptosis, with consequent reduction in tumor size. Administration of cyclopamine in a lethal, metastatic rodent model of prostate cancer completely abrogates systemic metastases and dramatically improves survival.

Technical Data:

M.Wt: 411.63

Formula: C₂₇H₄₁ NO₂

Solubility: Soluble to 5 mM in ethanol

Purity: >98%

Storage: Dessicate at -20 °C for 2 years

CAS No.: 4449-51-8

Related Products by Target:

GDC-0449

References for Cyclopamine:

1. Wilson, S. R., Strand, M. F., Krapp, A., Rise, F., Petersen, D., and Krauss, S. Hedgehog antagonist cyclopamine isomerizes to less potent forms when acidified. J Pharm Biomed Anal, 52: 707-713.

2. Mimeault, M., Johansson, S. L., Henichart, J. P., Depreux, P., and Batra, S. K. Cytotoxic effects induced by docetaxel, gefitinib, and cyclopamine on side population and nonside population cell fractions from human invasive prostate cancer cells. Mol Cancer Ther, 9: 617-630.

3. Hamon, F., Renoux, B., Chadeneau, C., Muller, J. M., and Papot, S. Study of a cyclopamine glucuronide prodrug for the selective chemotherapy of glioblastoma. Eur J Med Chem, 45: 1678-1682.

4. Kawahara, T., Kawaguchi-Ihara, N., Okuhashi, Y., Itoh, M., Nara, N., and Tohda, S. Cyclopamine and quercetin suppress the growth of leukemia and lymphoma cells. Anticancer Res, 29: 4629-4632, 2009.

5. Heretsch, P., Rabe, S., and Giannis, A. Synthesis of all diastereomers of the piperidine--alkaloid substructure of cyclopamine. Org Lett, 11: 5410-5412, 2009.

6. Giannis, A., Heretsch, P., Sarli, V., and Stossel, A. Synthesis of cyclopamine using a biomimetic and diastereoselective approach. Angew Chem Int Ed Engl, 48: 7911-7914, 2009.

7. Winkler, J. D., Isaacs, A., Holderbaum, L., Tatard, V., and Dahmane, N. Design and synthesis of inhibitors of Hedgehog signaling based on the alkaloid cyclopamine. Org Lett, 11: 2824-2827, 2009.

Certificate of Analysis/MSDS is available upon request with lot number