GSK-503 was designed by performing high-throughput screening for EZH2 methyltransferase inhibiting compounds followed by chemical optimization.In a melanoma mouse model, conditional Ezh2 ablation as much as treatment with the preclinical EZH2 inhibitor GSK503 stabilizes the disease through inhibition of growth and virtually abolishes metastases formation without affecting normal melanocyte biology.GSK-503 inhibits the methyltransferase activity of WT and mutant EZH2 with similar potency and is structurally related to GSK-126 and GSK-343. GSK-503 was > 200 fold selective over EZH1 (Kappi=636nM) and > 4000 fold selective over other histone methyltransferases.
|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.
The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors.
Zingg D, et al. Nat Commun. 2015 Jan 22;6:6051. PMID: 25609585.
|Related Histone Methyltransferase Products|
MI-503 is a potent and selective Menin-MLL inhibitor with IC50 of 14.7 nM.
MI-463 is a highly potent and orally bioavailable small molecule inhibitor of the Menin-MLL interaction, with an IC50 value of 15.3 nM.
MI-2 (Menin-MLL Inhibitor 2) is a potent menin-MLL interaction inhibitor with IC50 of 446±28 nM.
WDR5-0103 is a small molecule that binds a peptide-binding pocket on WDR5 (Kd = 450 nM), inhibiting the catalytic activity of the MLL core complex in vitro (IC50 = 39 µM).
MS023 is a potent and selective, cell-active inhibitor of type I PRMTs with IC50s of 4-119 nM.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.