T1-44

T1-44 is a selective small-molecule inhibitor of Protein Arginine Methyltransferase 5 (PRMT5). PRMT5 is an epigenetic enzyme that catalyzes the symmetric dimethylation of arginine residues on both histone and non-histone proteins, thereby regulating gene transcription, RNA splicing, and signal transduction pathways. Overexpression of PRMT5 is associated with poor prognosis in several malignancies, including pancreatic and prostate cancers. T1-44 works by blocking the enzymatic activity of PRMT5, which leads to the modulation of genes involved in cell migration, the extracellular matrix, and apoptosis. Preclinical studies have demonstrated that T1-44 can inhibit tumor invasion and improve survival in murine models of pancreatic cancer, particularly when used in combination with TGF-β signaling inhibitors like vactosertib. The compound was identified through research involving the University of Oxford and the GILO Foundation.