GSK3368715 (EPZ019997, GSK-3368715) dihydrochloride is a potent, reversible and SAM uncompetitive type I PRMT inhibitor with Kiapp of 1.5 to 81 nM for PRMT1, 3, 4, 6, and 8.
GSK3368715 (EPZ019997, GSK-3368715) dihydrochloride is a potent, reversible and SAM uncompetitive type I PRMT inhibitor with Kiapp of 1.5 to 81 nM for PRMT1, 3, 4, 6, and 8.
GSK3368715 displays minimal inhibition against a panel of lysine methyltransferases, and no inhibition against type II and type III PRMTs.
GSK3368715 displays time-dependent inhibition of all the type I PRMTs except PRMT3, binds in the peptide site directly adjacent to the SAM pocket.
GSK3368715 demonstrated anti-proliferative activity against all cancer cell lines and primary patient samples; produces synergistic cancer cell growth inhibition when combined with PRMT5 inhibitor GSK3203591.
GSK3368715 induced an interferon gene signature, amplified responses to interferon and innate immune signaling pathways, and decreased expression of the immunosuppressive cytokine VEGF.
