Uses
GSK3368715 trihydrochloride (EPZ019997) is an orally active, reversible, and S-adenosyl-L-methionine (SAM) uncompetitive type I protein arginine methyltransferases (PRMTs) inhibitor (IC50=3.1 nM (PRMT1), 48 nM (PRMT3), 1148 nM (PRMT4), 5.7 nM (PRMT6), 1.7 nM (PRMT8)). GSK3368715 trihydrochloride (EPZ019997) produces a shift in arginine methylation states, alters exon usage, and has strong anti-cancer activity[1].
Biological Activity
GSK3368715 is a potent inhibitor of type I protein arginine methyltransferases (PRMT) that inhibits PRMT1, 3, 4, 6 and 8 with Kiapp vaules ranging from 1.5 to 81 nM.
GSK3368715 is a potent, reversible, SAM uncompetitive inhibitor of type I PRMTs that produces a shift in arginine methylation states on hundreds of substrates from ADMA to MMA and SDMA. As a monotherapy, GSK3368715 induces anti-proliferative effects on cell lines from a broad range of hematological and solid tumor types in vitro.[1]
GSK3368715 has potent, anti-proliferative activity across cell lines representing a range of solid and hematological malignancies and can completely inhibit tumor growth or cause regressions of tumor models in vivo.[1]
in vivo
GSK3368715 trihydrochloride (EPZ019997) significantly effects on the growth of BxPC3 xenografts at all doses tested, reducing tumor growth by 78% and 97% in the 150- and 300-mg/kg dose groups, respectively[1].
IC 50
PRMT4: 1148 nM (IC50); PRMT3: 48 nM (IC50); PRMT1: 3.1 nM (IC50); PRMT6: 5.8 nM (IC50); PRMT8: 1.7 nM (IC50)
References
[1] Andrew Fedoriw, et al. Cancer Cell. 2019 Jul 8;36(1):100-114.e25.
