PRT808

PRT808 is a brain-penetrant, orally bioavailable small molecule inhibitor of Protein Arginine Methyltransferase 5 (PRMT5), developed by Prelude Therapeutics. PRMT5 is an enzyme that catalyzes the symmetric dimethylation of arginine residues on histone and non-histone proteins, a process often upregulated in various cancers, including glioblastoma (GBM). By inhibiting PRMT5, PRT808 reduces symmetrical dimethylation (SDMA) protein marks, leading to splicing aberrations in oncogenes and regulatory factors, induction of apoptosis, and inhibition of cell proliferation. Research has demonstrated its efficacy in genetically and epigenetically diverse patient-derived glioma stem cells (GSCs), regardless of MTAP status, though sensitivity may be influenced by p53 mutation status.