WAY 316606 (hydrochloride)

WAY 316606 hydrochloride is an inhibitor of the secreted protein sFRP-1, an endogenous antagonist of the secreted glycoprotein Wnt. The affinity of WAY-316606 for sFRP-1 is determined using the FP binding assay with IC₅₀ of 0.5 μM^[1]. IC50 & Target:IC50: 0.5 μM (sFRP-1)^[1] In Vitro:The EC₅₀ of WAY-316606 for Wnt-Luciferase Activity from U2-OS Cells is 0.65 μM^[1].
WAY-316606 binds to secreted frizzled-related protein (sFRP)-1 inhibitor with a K_D of 0.08 μM and inhibits sFRP-1 with an EC₅₀ of 0.65 μM. WAY-316606 also binds to sFRP-2, albeit over 10 times weaker with a K_D of 1 μM. Using a fluorescence polarization binding assay that employs a fluorescent probe compound and purified human sFRP-1 protein in a competitive-binding format, the IC₅₀ for WAY-316606 is 0.5 μM^[2]. In Vivo:WAY-316606 increases bone formation when tested in a neonatal murine calvarial assay. WAY-316606 increases total bone area up to 60% in a dose-dependent manner with an EC₅₀ of about 1 nM. WAY-316606 has good aqueous solubility, moderate to low inhibition of cytochrome p450 isozymes (3A4, 2D6, 2C9) and good stability in rat and human liver microsomes (t_1/2>60 min in each species)^[1].
In female Sprague-Dawley rats, WAY-316606 exhibits high plasma clearance (77 mL/min/kg, greater than hepatic blood flow) following a single intravenous bolus dose (2 mg/kg), which results in a rapid decline of drug exposure in the plasma despite the route of administration^[2].