GSK3368715

GSK3368715 is a first-in-class, orally active, reversible inhibitor of type I protein arginine methyltransferases (PRMTs), with potent anti-proliferative activity across a range of solid and hematological malignancies. It acts as an S-adenosylmethionine (SAM)-uncompetitive inhibitor that binds to the protein substrate binding pocket of type I PRMTs, including PRMT1, PRMT3, PRMT4, PRMT6, and PRMT8. Inhibition leads to reduced intracellular asymmetric dimethylarginine (ADMA) levels and accumulation of monomethylarginine (MMA) and symmetric dimethylarginine (SDMA). Preclinical studies demonstrated strong anti-tumor effects in multiple cancer models. The drug was developed for oncology indications but clinical development was terminated due to safety concerns related to thromboembolic events[2][5][7].