Fig. 6: PRT382, a selective inhibitor of PRMT5.

a Chemical structure of tool compound PRT382, an in vitro and in vivo PRMT5 inhibitor. Structural comparison is shown between recently developed PRMT5 inhibitors EZP015666 (SAM non-competitive) and JNJ-64619178, LLY-283, and PF-06855800 (SAM-competitive). b Selectivity of PRT382 for PRTM5 in contrast to other methyltransferases and PRMT family members. Circle size represents percent inhibition at 10 μM. c Filtration binding assays in the presence of recombinant human PRMT5/MEP50 and histone H2A. Plot is representative of n = 3 experiments. d Reducing sDMA assay in the Granta-519 lymphoma cell line. Plot is representative of N = 3 experiments. e Anti-proliferative activity, measured as IC₅₀, of PTR382 against a leukemia and lymphoma immortalized cell lines. f Dose-dependent proliferation decrease with a panel of B-lymphoma cell lines (n = 3 independent experiments) upon PRMT5 inhibition with increasing doses of PRT382 for 72 h as measured by MTS assay. g PRT382 was formulated in 0.5% carboxymethylcellulose sodium salt + 0.5% Tween80 as a 1 mg/mL suspension for 10 mg/kg and was administered in a 10 mL/kg dose volume by oral gavage to CD-1 mice. Blood was collected at indicated time points and analyzed by LC-MS/MS. In vivo delivery of PRT382 at 10, 30, and 100 mg/kg was well-tolerated in WT CD-1 mice and led to peak plasma levels of 12, 32, and 75 µM, respectively (n = 3 biologically independent animals per group). Blood concentrations are reported as the mean +/−SD. Source data are provided as a Source Data file.