Cyclopamine-KAAD

Biological Activity

Cyclopamine-KAAD (Cyc-KAAD), a cell-permeable derivative of cyclopamine, acts as a potent antagonist of Hedgehog signaling by targeting Smoothened (Smo) protein. Compared with the parental compound, Cyc-KAAD has 10-20-fold higher potency in inhibition of β-galactosidase expression in p2^Ptch-/-cells with similar or lower toxicity, as well as exhibits greater potency in suppression of ShhNp-induced pathway activity ^[1]. Cyc-KAAD decreases the expression of Gli1 and PTCH1, thus resulting in inhibition of cell growth and induction of apoptosis both in advanced gastric cancer cells ^[2] and esophageal cancer cells ^[3]. Cyc-KAAD also markedly inhibits cell proliferation and causes significant attenuation in invasiveness and motility of human hepatocellular carcinoma (HCC) cells, which demonstrates that blockade of the Hh signaling pathway may be a potential target of new therapeutic strategy for HCC ^[4-5]. Cyc-KAAD facilitates TRAIL-mediated apoptosis at the level of the intrinsic and extrinsic apoptotic pathways in malignant glioma cells ^[6].

Chemical Properties

Cas No.: 306387-90-6	M. Wt.: 697.99
Formula: C44H63N3O4	Purity: ≥80%(HPLC)
Synonym: Cyc-KAAD, KAAD-cyclopamine
Chemical Name: 3-Keto-N-aminoethyl-N’-aminocaproyldihydrocinnamoyl cyclopamine
Appearance: Pale yellow solid
Solubility: Soluble in DMSO (5 mg/mL) or EtOH (1 mg/mL)
Storage: Store solid at -20 ºC for the stability of two years, protect from light.

The appropriate working concentration of Cyclopamine-KAAD depends on cell types, cell culture properties and specific applications. It is recommended that researchers start with optimal experiments for first use.