prt811

PRT811 is a potent, selective, orally bioavailable, and brain-penetrant small molecule inhibitor of protein arginine methyltransferase 5 (PRMT5). It acts as a SAM-competitive inhibitor, binding to PRMT5 and inhibiting its enzymatic activity. PRMT5 catalyzes symmetric arginine dimethylation of protein substrates involved in histone modification, transcription regulation, and spliceosome assembly. Overexpression of PRMT5 is associated with tumor cell growth and poor clinical outcomes. PRT811 has demonstrated broad antiproliferative activity in preclinical models across glioblastoma multiforme (GBM), breast cancer, lung cancer, and melanoma. Clinically, it has shown preliminary efficacy in patients with recurrent high-grade glioma (especially IDH-mutant) and advanced/metastatic uveal melanoma during phase 1 trials. The drug was originally developed by Prelude Therapeutics and later licensed worldwide to Pathos AI for further development.