product name SANT-1
Description: SANT-1 is a potent and selective Sonic hedgehog (Shh) enzyme inhibitor with potential anticancer activities. SANT-1 directly binds to Smoothened (Smo) receptor with Kd of 1.2 nM and inhibits Smo agonist effects with IC50 of 20 NM. Sonic hedgehog (Shh) is expressed in AML biopsies and is essential for the drug resistance of cancer stem cells of AML.
References: Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14071-6; PLoS One. 2009;4(4):e5182.
373.49
Formula
C23H27N5
CAS No.
304909-07-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 21 mg/mL (56.2 mM)
Water: <1 mg/mL
Ethanol: 20 mg/mL (53.5 mM)
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19426263
| In Vitro |
In vitro activity: SANT-1 inhibits wild type and oncogenic Smo with equal potency. SANT-1 counteracts SAG-induced pathway activation in Shh-LIGHT2 cells. SANT-1 is able to block BODIPY-cyclopamine binding to Smo-expressing cells, but SANT-1 is unable to inhibit completely this association to background levels. This suggests that their interactions with Smo may alter its affinity for cyclopamine rather than compete directly for cyclopamine binding. SANT-1 blocks pathway activation in SmoA1-LIGHT2 cells with potencies similar to those observed in the Shh-LIGHT2 assay. SANT-1 has disparate inhibitory activities in the Shh-LIGHT2 and BODIPY-cyclopamine assays and is unusually potent at blocking SAG-mediated pathway activation. SANT-1 efficiently inhibited cyclopamine- and jervine- induced translocation of Smo to the primary cilium. SANT-1 inhibits PKA stimulation of Smo trafficking to the proximal cilium. When combined HDAC inhibitor SAHA, SANT-1 is able to suppress cellular proliferation and colony formation of Gemcitabine-resistant pancreatic adenocarcinoma cell lines Panc-1 and BxPC-3. Kinase Assay: Cell Assay: In tumor pancreas cancer cell line, SANT-1 inhibited Panc-1 cell lines with an IC50 value of 100 µM after incubation. In addition, a combination application of SANT-1 and SAHA (histone deacetylase inhibitor) enhancement the anti-tumor effectives of treatment as a result of their cooperative suppression of the Hh pathway activity |
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| Formulation & Dosage | |
| References | Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14071-6; PLoS One. 2009;4(4):e5182. |
