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    Smoothened Agonist (SAG)
    Smoothened Agonist (SAG)

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V1338
    CAS #: 912545-86-9Purity ≥98%

    Description: Smoothened Agonist (SAG), a benzothiophene analog, is a potent and cell-permeable Smoothened (Smo) agonist with EC50 of 3 nM in Shh-LIGHT2 cells. SAG potently activates the Hedgehog signaling pathway in Shh-light 2 cells (EC50 ~ 3 nM). SAG induces pathway activation independently of Ptch proteins. The Smoothened receptor (SMO) mediates signal transduction in the hedgehog pathway, which is implicated in normal development and carcinogenesis. SMO antagonists can suppress the growth of some tumors. 

    References: Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14071-6; Neurosci Lett. 2010 Sep 27;482(2):81-5.

    Related CAS #: 912545-86-9 (free base); 2095432-58-7 (HCl)   

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    Molecular Weight (MW)490.06
    FormulaC28H28ClN3OS 
    CAS No.912545-86-9
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 71 mg/mL (134.8 mM)
    Water: N/A
    Ethanol: 40 mg/mL (75.9 mM)
    Other info

    Chemical Name: 3-chloro-N-((1r,4r)-4-(methylamino)cyclohexyl)-N-(3-(pyridin-4-yl)benzyl)benzo[b]thiophene-2-carboxamide

    SMILES Code: O=C(C1=C(Cl)C2=CC=CC=C2S1)N([[email protected]]3CC[[email protected]](NC)CC3)CC4=CC=CC(C5=CC=NC=C5)=C4 

    Exact Mass: 489.16416 

    Synonyms

    SAG free base; SAG; SAG (cyclopamine antagonist);SAG (Smo agonist)


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    In Vitro

    In vitro activity: SAG regulates Smo activity by binding directly to the Smo heptahelical bundle. SAG induces Smo-dependent signaling through Gli in a GRK2-dependent way. SAG also (1 nM) induces proliferation of neuronal and glial precursors without affecting the differentiation pattern of newly produced cells.


    Cell Assay: SAG acts downstream of Ptch1 in the Hh pathway and counteracts cyclopamine inhibition of Smo. SAG induces firefly luciferase expression in Shh-LIGHT2 cells with an EC50 of 3 nM and then inhibits expression at higher concentrations. In Smo-expressing Cos-1 cells, SAG yields an apparent dissociation constant (KD) of 59 nM for the SAG/Smo complex.

    In VivoIn the adult rat hippocampus, the intracerebroventricular administration of SAG (2.5 nM) significantly increases the number of newly generated cells and extends survival of hippocampal cells. In mice, SAG (20 μg/g, i.p.) effectively prevents GC-induced neonatal cerebellar developmental abnormalities.
    Animal modelRats and mice
    Formulation & DosageRats: 2.5 nM, intracerebroventricular administration; Mice: 20 μg/g, i.p.
    References

    Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14071-6; Neurosci Lett. 2010 Sep 27;482(2):81-5.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

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