Stemolecule™ KAAD-Cyclopamine

Stemolecule KAAD-Cyclopamine is a sonic hedgehog antagonist known to target Smoothened¹. Hedgehog signaling is involved in embryogenesis as well as cancer progression². KAAD-Cyclopamine has been utilized to halt the migration or proliferation of a variety of cancer cells (e.g., esophageal, gastrointestinal, hepatic and pancreatic cancer)^3-6.

Product Name: Stemolecule KAAD-Cyclopamine

Catalog Number: 04-0028

Size: 100 µg

Alternate Name(s): N-[2-[(3'R,7'aR)-3',6',10,11b-tetramethyl-3-oxospiro[1,2,4,6,6a,6b,7,8, 11,11a-decahydrobenzo[a]fluorene-9,2'-3,3a,5,6,7,7a-hexahydrofuro[3, 2-b]pyridine]-4'-yl]ethyl]-6-(3-phenylpropanoylamino)hexanamide

Chemical Formula: C₄₄H₆₃N₃O₄

Molecular Weight: 697.99

CAS Number: 306387-90-6

Purity: Greater than 95% by TLC analysis

Formulation: Pale yellow solid

Solubility: For a 10 mM concentrated stock solution of KAAD-Cyclopamine, reconstitute the compound by adding 14.3 µL of DMSO to the entire contents of the vial. If precipitate is observed, warm the solution to 37 °C for 2 to 5 minutes. For cell culture, the media should be prewarmed prior to adding the reconstituted compound. Note: for most cells, the maximum tolerance to DMSO is less than 0.5%. This molecule is soluble in DMSO at 10 mM, ethanol at 1.4 mM, and methanol at 1.4 mM.

Storage and Stability: Store powder at 4 °C protected from light. Information about the stability of Stemolecules in solution is largely not available. As a general guideline, we recommend that stock solution be freshly made and stored in aliquots at −20 °C, protected from light. The effect of storage of stock solutions should be verified for each application.

Quality Control: The purity of KAAD-Cyclopamine was determined by TLC analysis. The accurate mass was determined by mass spectrometry. Cellular toxicity of KAAD-Cyclopamine was tested on mouse embryonic stem cells.

Documents

Specification Sheets:

• 04-0028 Specifications Sheet

Safety Data Sheets:

• 04-0028 Safety Data Sheet

References

1. Pasca di Magliano, M., and Hebrok, M. Hedgehog signalling in cancer formation and maintenance. Nat Rev Cancer 3: 903-911 (2003).
2. Jiang, J., and Hui, C.C. Hedgehog signaling in development and cancer. Dev Cell 15: 801-812 (2008).
3. Ma, X., Chen, K., Huang, S., Zhang, X., Adegboyega, P.A., Evers, B.M., Zhang, H., and Xie, J. Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas. Carcinogenesis 26: 1698-1705 (2005).
4. Ma, X., Sheng, T., Zhang, Y., Zhang, X., He, J., Huang, S., Chen, K., Sultz, J., Adegboyega, P.A., Zhang, H., and Xie, J. Hedgehog signaling is activated in subsets of esophageal cancers. Int J Cancer 118: 139-148 (2006).
5. Sicklick, J.K., Li, Y.X., Jayaraman, A., Kannangai, R., Qi, Y., Vivekanandan, P., Ludlow, J.W., Owzar, K., Chen, W., Torbenson, M.S., and Diehl, A.M. Dysregulation of the Hedgehog pathway in human hepatocarcinogenesis. Carcinogenesis 27: 748-757 (2006).
6. Cheng, W.T., Xu, K., Tian, D.Y., Zhang, Z.G., Liu, L.J., and Chen, Y. Role of Hedgehog signaling pathway in proliferation and invasiveness of hepatocellular carcinoma cells. Int J Oncol 34: 829-836 (2009).

Additional Publicatons

• Rajaei B; Massumi M; Wheeler M. Glucose‐Responsiveness of Pancreatic β‐Like (GRP β‐L) Cells Generated from Human Pluripotent Stem Cells. Current Protoclos Human Genetics 100:e71 (2019).
• Ogaki S; Morooka M; Otera K; Kume S. A cost-effective system for differentiation of intestinal epithelium from human induced pluripotent cells. Sci Rep5:17297 (2015).
• Toivonen S; Lundin K; Balboa D; Ustinov J; Tamminen K; Palgi J; Trokovic R; Tuuri T; Otonkoski T. Activin A and Wnt-dependent specification of human definitive endoderm cells. Exp Cell Res319:2535 (2013).