PRT382 (PRT-382) is a potent, selective and SAM-competitive PRMT5 inhibitor with IC50 of 2.8 nM in filtration binding assays with recombinant human PRMT5/MEP50 and histone H2A as the protein substrate.
PRT382 displays no significant activity against 38 other methyltransferases (e.g DNMTs, MLL1-4 complexes, EZH1 and EZH2 complexes, NRMTs, NSD, SUVs, SMYs, SETs, PRDM9), and other members of the PRMT family.
PRT382 exhibits an IC50 of 27 nM in a reducing sDMA assay in the Granta-519 lymphoma cell line.
PRT382 demonstrated anti-proliferative efficacy in the leukemia and lymphoma cell lines CCMCL-1, JVM-2, U-2932, RL, and KARPAS-422 with IC50 values of 0.01-0.5 uM.
PRT382 demonstrated low clearance and high oral bioavailability in mice, rats, and dogs (F% = 70–80%), and high AUC levels (1175 h*kg*ng/mL/mg) in mice.|
PRT382 demonstrated anti-proliferative potency in HG3 and Mec-1 cells when compared to SAM-competitive PRMT5 inhibitor compounds JNJ-64619178, LLY-283, and PF-06855800.
PRT382 (10 mg/kg, 0.5% methylcellulose) displayed antileukemic activity in an aggressive model of CLL/RT.