Biological Activity
epz020411 is an inhibitor of prmt6.prmt6, a member of the protein arginine methyltransferasefamily, comprises 45 enzymes. the post-translational modifications of prmt6 are important regulators of rna processing, transcriptional regulation, and signal transduction.
in vitro
in biochemical assays, epz020411 was found to be over 100-fold selective for prmt6/8/1 compared to other histone methyltransferases, such as prmt3, prmt4, prmt5 and prmt7. in addition, epz020411 treatment led to a dose-dependent decrease in h3r2 methylation, while treatment with its prmt6-inactive analog did not generate an ic50 at concentrations up to 20 μm [1].
in vivo
animal study found that male sd rats i.v. administered a single dose of epz020411 at 1 mg/kg showed a moderate clearance of 19.7 ml/min/kg, with a volume of distribution at steady state of 11.1 l/kg, and a mean terminal half-life of 8.54 h. following 5 mg/kg s.c. dosing, a good bioavailability of 65.6 was observed, resulting in epz020411 unbound concentration remaining over the prmt6 ic50 for more than 12 h [1].
References
[1] mitchell lh, et al. aryl pyrazoles as potent inhibitors of arginine methyltransferases: identification of the first prmt6 toolcompound. acs med chem lett. 2015 apr 6;6(6):655-659.
