An inhibitor of type I PRMTs
GSK3368715 is an inhibitor of type I protein arginine methyltransferases (PRMTs; IC50s = 3.1, 162, 38, 4.7, and 39 nM for PRMT1, 3, 4, 6, and 8, respectively).1 It is selective for type I PRMTs over PRMT5, 7, and 9 (IC50s = >20,408, >40,000, and >15,000 nM, respectively), as well as 20 additional methyltransferases and a panel of ion channels, receptors, and transporters at 10 ?M. GSK3368715 (5 ?M) inhibits the growth of patient-derived diffuse large B cell lymphoma (DLBCL) cells. In vivo, GSK3368715 (9.375-150 mg/kg) reduces tumor volume in Toledo DLBCL and BxPC-3 pancreatic adenosarcoma mouse xenograft models. It also reduces tumor growth in ACHN renal carcinoma and MDA-MB-468 breast cancer mouse xenograft models and a pancreatic adenocarcinoma patient-derived xenograft (PDX) mouse model when administered at doses of 150 and 300 mg/kg, respectively.
1.Fedoriw, A., Rajapurkar, S.R., O'Brien, S., et al.Anti-tumor activity of the type I PRMT inhibitor, GSK3368715, synergizes with PRMT5 inhibition through MTAP lossCancer Cell36(1)100-114.e125(2019)
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