Cyclopamine
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MedKoo CAT#: 401235

CAS#: 4449-51-8

Description: Cyclopamine, also known as 11-deoxojervine, is a naturally occurring chemical that belongs to the group of steroidal jerveratrum alkaloids. It is a teratogen isolated from the corn lily (Veratrum californicum) that causes usually fatal birth defects. It can prevent the fetal brain from dividing into two lobes (holoprosencephaly) and cause the development of a single eye (cyclopia). It does so by inhibiting the hedgehog signaling pathway (Hh). Cyclopamine is useful in studying the role of Hh in normal development, and as a potential treatment for certain cancers in which Hh is overexpressed. Cyclopamine was named for one-eyed lambs which were born to sheep which grazed on wild corn lily at a farm in Idaho.


Chemical Structure

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Cyclopamine
CAS# 4449-51-8

Theoretical Analysis

MedKoo Cat#: 401235
Name: Cyclopamine
CAS#: 4449-51-8
Chemical Formula: C27H41NO2
Exact Mass: 411.31
Molecular Weight: 411.620
Elemental Analysis: C, 78.78; H, 10.04; N, 3.40; O, 7.77

Price and Availability

Size Price Availability Quantity
50mg USD 450 2 weeks
100mg USD 650 2 weeks
500mg USD 1450 2 weeks
1g USD 2650 2 weeks
2g USD 4650 2 weeks
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Synonym: HSDB-3505; HSDB 3505; HSDB-3505; Cyclopamine; 11-Deoxojervine.

IUPAC/Chemical Name: (2'R,3S,3'R,3a'S,6aS,6bS,6'S,7a'R,11aS,11bR)-3',6',10,11b-tetramethyl-1,2,3,3a',4,4',5',6,6a,6b,6',7,7',7a',8,11,11a,11b-octadecahydro-3'H-spiro[benzo[a]fluorene-9,2'-furo[3,2-b]pyridin]-3-ol

InChi Key: QASFUMOKHFSJGL-LAFRSMQTSA-N

InChi Code: InChI=1S/C27H41NO2/c1-15-11-24-25(28-14-15)17(3)27(30-24)10-8-20-21-6-5-18-12-19(29)7-9-26(18,4)23(21)13-22(20)16(27)2/h5,15,17,19-21,23-25,28-29H,6-14H2,1-4H3/t15-,17+,19-,20-,21-,23-,24+,25-,26-,27-/m0/s1

SMILES Code: O[C@@H]1CC2=CC[C@]3([H])[C@]([C@@]2(C)CC1)([H])CC4=C(C)[C@@]5(O[C@@]6([H])[C@@]([C@H]5C)([H])NC[C@@H](C)C6)CC[C@@]34[H]

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: Cyclopamine is currently being investigated as a treatment agent in basal cell carcinoma, medulloblastoma, and rhabdomyosarcoma, tumors that result from excessive Hh activity, glioblastoma, and as a treatment agent for multiple myeloma. Studies suggest that cyclopamine acts as a primary inhibitor of the so-called "hedgehog" signal-transduction pathway in cells. This pathway named for the ligand for the signal protein, is used by cells to help them react to external chemical signals. The pathway carries out important functions in embryonic development and when it goes awry, deformities can occur. However, errant activation of the pathway can also trigger cancer in adult humans, leading to basal cell carcinoma, medulloblastoma, rhabdomyosarcoma, and prostate, pancreatic and breast cancers. A way of controlling the pathway using cyclopamine could turn this problem on its head and provide a way to treat cancer. Many anticancer drugs are paradoxically carcinogenic in healthy individuals. The cyclopamine derivative IPI-926 is in clinical trials for the treatment of various types of cancer.  [source: http://en.wikipedia.org/wiki/Cyclopamine).      

Product Data:
Biological target: Cyclopamine is a Hedgehog (Hh) pathway antagonist with an IC50 of 46 nM in the Hh cell assay.
In vitro activity: Finally, cyclopamine also significantly improved the tumor growth inhibition effect of i.v.-injected nanotherapeutics in pancreatic tumor xenograft mouse models. Reference: Biomaterials. 2016 Oct;103:12-21. https://pubmed.ncbi.nlm.nih.gov/27376555/
In vivo activity: The number of apoptotic cells in the BPH and cyclopamine rat groups were significantly reduced compared with the control group (P<0.05). Conversely, the number of apoptotic cells in the cyclopamine group was significantly increased (P<0.05) than that of the BPH group. These results suggested that cyclopamine could induce the apoptosis of epithelial cells in BPH rats. Reference: Int J Mol Med. 2020 Jul; 46(1): 311–319. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255449/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 10.0 24.29
DMF 2.0 4.86
Ethanol 17.4 42.34
Ethanol:PBS (pH 7.2) (1:3) 0.3 0.61

Preparing Stock Solutions

The following data is based on the product molecular weight 411.62 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Yuan YF, Zhu WX, Liu T, He JQ, Zhou Q, Zhou X, Zhang X, Yang J. Cyclopamine functions as a suppressor of benign prostatic hyperplasia by inhibiting epithelial and stromal cell proliferation via suppression of the Hedgehog signaling pathway. Int J Mol Med. 2020 Jul;46(1):311-319. doi: 10.3892/ijmm.2020.4569. Epub 2020 Apr 8. PMID: 32319534; PMCID: PMC7255449. 2. Song X, Zhang B, Taorong W, Wang G, Huang Y, Zhang Y, Liu M, Chen X. Effects of Cyclopamine on the Viability of Articular Chondrocytes in Rats with Adjuvant Arthritis in vitro. Ann Clin Lab Sci. 2020 Jan;50(1):85-91. PMID: 32161016. 3. Zhang B, Jiang T, Shen S, She X, Tuo Y, Hu Y, Pang Z, Jiang X. Cyclopamine disrupts tumor extracellular matrix and improves the distribution and efficacy of nanotherapeutics in pancreatic cancer. Biomaterials. 2016 Oct;103:12-21. doi: 10.1016/j.biomaterials.2016.06.048. Epub 2016 Jun 23. PMID: 27376555. 4. Li R, Cai L, Ding J, Hu CM, Wu TN, Hu XY. Inhibition of hedgehog signal pathway by cyclopamine attenuates inflammation and articular cartilage damage in rats with adjuvant-induced arthritis. J Pharm Pharmacol. 2015 Jul;67(7):963-71. doi: 10.1111/jphp.12379. Epub 2015 Feb 3. PMID: 25645065.
In vitro protocol: 1. Yuan YF, Zhu WX, Liu T, He JQ, Zhou Q, Zhou X, Zhang X, Yang J. Cyclopamine functions as a suppressor of benign prostatic hyperplasia by inhibiting epithelial and stromal cell proliferation via suppression of the Hedgehog signaling pathway. Int J Mol Med. 2020 Jul;46(1):311-319. doi: 10.3892/ijmm.2020.4569. Epub 2020 Apr 8. PMID: 32319534; PMCID: PMC7255449. 2. Song X, Zhang B, Taorong W, Wang G, Huang Y, Zhang Y, Liu M, Chen X. Effects of Cyclopamine on the Viability of Articular Chondrocytes in Rats with Adjuvant Arthritis in vitro. Ann Clin Lab Sci. 2020 Jan;50(1):85-91. PMID: 32161016.
In vivo protocol: 1. Zhang B, Jiang T, Shen S, She X, Tuo Y, Hu Y, Pang Z, Jiang X. Cyclopamine disrupts tumor extracellular matrix and improves the distribution and efficacy of nanotherapeutics in pancreatic cancer. Biomaterials. 2016 Oct;103:12-21. doi: 10.1016/j.biomaterials.2016.06.048. Epub 2016 Jun 23. PMID: 27376555. 2. Li R, Cai L, Ding J, Hu CM, Wu TN, Hu XY. Inhibition of hedgehog signal pathway by cyclopamine attenuates inflammation and articular cartilage damage in rats with adjuvant-induced arthritis. J Pharm Pharmacol. 2015 Jul;67(7):963-71. doi: 10.1111/jphp.12379. Epub 2015 Feb 3. PMID: 25645065.

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1: Lee ST, Welch KD, Panter KE, Gardner DR, Garrossian M, Chang CW. Cyclopamine: from cyclops lambs to cancer treatment. J Agric Food Chem. 2014 Jul 30;62(30):7355-62. doi: 10.1021/jf5005622. Epub 2014 Apr 22. PMID: 24754790.


2: Iovine V, Mori M, Calcaterra A, Berardozzi S, Botta B. One Hundred Faces of Cyclopamine. Curr Pharm Des. 2016;22(12):1658-81. doi: 10.2174/1381612822666160112130157. PMID: 26759083.


3: Ma H, Li HQ, Zhang X. Cyclopamine, a naturally occurring alkaloid, and its analogues may find wide applications in cancer therapy. Curr Top Med Chem. 2013;13(17):2208-15. doi: 10.2174/15680266113139990153. PMID: 23978132.


4: Heretsch P, Tzagkaroulaki L, Giannis A. Cyclopamine and hedgehog signaling: chemistry, biology, medical perspectives. Angew Chem Int Ed Engl. 2010 May 3;49(20):3418-27. doi: 10.1002/anie.200906967. PMID: 20429080.


5: Miller SJ, Yu TC. Cyclopamine as a potential therapeutic agent for treatment of tumors related to hedgehog pathway mutations. Dermatol Surg. 2002 Feb;28(2):187. doi: 10.1046/j.1524-4725.2002.01179.x. PMID: 11860435.


6: Kuenzli S, Sorg O, Saurat JH. Cyclopamine, hedgehog and psoriasis. Dermatology. 2004;209(2):81-3. doi: 10.1159/000079588. PMID: 15316158.


7: Chen JK. I only have eye for ewe: the discovery of cyclopamine and development of Hedgehog pathway-targeting drugs. Nat Prod Rep. 2016 May 4;33(5):595-601. doi: 10.1039/c5np00153f. PMID: 26787175; PMCID: PMC4856577.


8: Carballo GB, Matias D, Ribeiro JH, Pessoa LS, Arrais-Neto AM, Spohr TCLSE. Cyclopamine sensitizes glioblastoma cells to temozolomide treatment through Sonic hedgehog pathway. Life Sci. 2020 Sep 15;257:118027. doi: 10.1016/j.lfs.2020.118027. Epub 2020 Jul 2. PMID: 32622951.


9: Risso-Ballester J, Galloux M, Cao J, Le Goffic R, Hontonnou F, Jobart-Malfait A, Desquesnes A, Sake SM, Haid S, Du M, Zhang X, Zhang H, Wang Z, Rincheval V, Zhang Y, Pietschmann T, Eléouët JF, Rameix-Welti MA, Altmeyer R. A condensate- hardening drug blocks RSV replication in vivo. Nature. 2021 Jul;595(7868):596-599. doi: 10.1038/s41586-021-03703-z. Epub 2021 Jul 7. PMID: 34234347.


10: Meth MJ, Weinberg JM. Cyclopamine: inhibiting hedgehog in the treatment of psoriasis. Cutis. 2006 Sep;78(3):185-8. PMID: 17036662.


11: Chianese G, Lopatriello A, Sirignano C, Andreani A, Gambini A, De Combarieu E, Stornaiuolo M, Taglialatela-Scafati O. Hydroxylated cyclopamine analogues from Veratrum californicum and their hedgehog pathway inhibiting activity. Bioorg Med Chem. 2023 Apr 15;84:117265. doi: 10.1016/j.bmc.2023.117265. Epub 2023 Mar 27. PMID: 37001245.


12: da Costa Fernandes CJ, Ferreira MR, Zambuzzi WF. Cyclopamine targeting hedgehog modulates nuclear control of the osteoblast activity. Cells Dev. 2023 Jun;174:203836. doi: 10.1016/j.cdev.2023.203836. Epub 2023 Mar 25. PMID: 36972848.


13: Turner MW, Cruz R, Mattos J, Baughman N, Elwell J, Fothergill J, Nielsen A, Brookhouse J, Bartlett A, Malek P, Pu X, King MD, McDougal OM. Cyclopamine bioactivity by extraction method from Veratrum californicum. Bioorg Med Chem. 2016 Aug 15;24(16):3752-7. doi: 10.1016/j.bmc.2016.06.017. Epub 2016 Jun 14. PMID: 27338657; PMCID: PMC4955791.


14: Yuan YF, Zhu WX, Liu T, He JQ, Zhou Q, Zhou X, Zhang X, Yang J. Cyclopamine functions as a suppressor of benign prostatic hyperplasia by inhibiting epithelial and stromal cell proliferation via suppression of the Hedgehog signaling pathway. Int J Mol Med. 2020 Jul;46(1):311-319. doi: 10.3892/ijmm.2020.4569. Epub 2020 Apr 8. PMID: 32319534; PMCID: PMC7255449.


15: Gould A, Missailidis S. Targeting the hedgehog pathway: the development of cyclopamine and the development of anti-cancer drugs targeting the hedgehog pathway. Mini Rev Med Chem. 2011 Mar;11(3):200-13. doi: 10.2174/138955711795049871. PMID: 21222574.


16: Bar EE, Stearns D. New developments in medulloblastoma treatment: the potential of a cyclopamine-lovastatin combination. Expert Opin Investig Drugs. 2008 Feb;17(2):185-95. doi: 10.1517/13543784.17.2.185. PMID: 18230052.


17: Song X, Zhang B, Taorong W, Wang G, Huang Y, Zhang Y, Liu M, Chen X. Effects of Cyclopamine on the Viability of Articular Chondrocytes in Rats with Adjuvant Arthritis in vitro. Ann Clin Lab Sci. 2020 Jan;50(1):85-91. PMID: 32161016.


18: Zhang B, Jiang T, Shen S, She X, Tuo Y, Hu Y, Pang Z, Jiang X. Cyclopamine disrupts tumor extracellular matrix and improves the distribution and efficacy of nanotherapeutics in pancreatic cancer. Biomaterials. 2016 Oct;103:12-21. doi: 10.1016/j.biomaterials.2016.06.048. Epub 2016 Jun 23. PMID: 27376555.


19: Zhang T, Li Y, Song Y, Chen X, Li J, Peng Q, He J, Fei X. Curcumin- and Cyclopamine-Loaded Liposomes to Enhance Therapeutic Efficacy Against Hepatic Fibrosis. Drug Des Devel Ther. 2020 Dec 23;14:5667-5678. doi: 10.2147/DDDT.S287442. PMID: 33380787; PMCID: PMC7767702.


20: Welch KD, Panter KE, Lee ST, Gardner DR, Stegelmeier BL, Cook D. Cyclopamine-induced synophthalmia in sheep: defining a critical window and toxicokinetic evaluation. J Appl Toxicol. 2009 Jul;29(5):414-21. doi: 10.1002/jat.1427. PMID: 19301244.