In vitro: GNE-477 (Compound 8) has improved potency in the MCF7.1 cell proliferation assay with an EC50 of 143 nM.
In vivo: GNE-477 also exhibits stasis in a PC3 tumor growth inhibition study. In an experiment evaluating the tumor growth inhibition of a PC3 tumor xenograft over 14 days, stasis is achieved at a 20 mg/kg QD dose and significant inhibition is observed with doses as low as 1 mg/kg QD. GNE-477 is generally well tolerated during this study as demonstrated by acceptable levels of weight loss comparable to that observed with the animals in the vehicle cohort.
|Formulation||0.5% methylcellulose/0.2% Tween-80|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||9.2 mg/mL in DMSO|
Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor.
Heffron TP, et al. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2408-11. PMID: 20346656.
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