SAG dihydrochloride is a potent Smoothened (Smo) receptor agonist (EC50=3 nM; Kd=59 nM). SAG dihydrochloride activates the Hedgehog signaling pathway and counteracts Cyclopamine (HY-17024) inhibition of Smo[2].IC50 & Target: EC50: 3 nM (Smo)In Vitro: SAG (0.1 nM-100 μM; 30 h) induces firefly luciferase expression in Shh-LIGHT2 cells with an EC50 of 3 nM and then inhibits expression at higher concentrations.
SAG (1-1000 nM; 1 h) competes for the binding of BODIPY-cyclopamine to Smo-expressing Cos-1 cells, yielding an apparent dissociation constant (Kd) of 59 nM for the SAG/Smo complex.
SAG (100 nM) inhibits the inhibitory effect of ShhN-induced pathway activation by Robotnikinin[2].
SAG (250 nM; 48 h) significantly increases SMO mRNA and protein expression in MDAMB231 cells.
SAG (250 nM; 24 and 48 h) increases CAXII mRNA expression in MDAMB231 cells at 24h in normoxic and hypoxic conditions in MDAMB231 cells.
SAG (250 nM; 24 h) increases MDAMB231 cells migration.In Vivo: SAG (1.0 mM) induces more osteogenesis mainly at the defect borders and a significant increase in BV/TV at the eight week timepoint in CD-1 mice.
SAG (15-20 mg/kg; i.p.) induces pre-axial polydactyly prevalently in a dose-dependent manner in mice.