GSK3326595

GSK3326595 is an inhibitor of protein arginine methyltransferase 5 (PRMT5). It inhibits methylation of peptides derived from the PRMT5 substrates histone H4 and H2A, SmD3, FUBP1, and HNRNPH1 by the PRMT5/MEP50 complex with IC50 values ranging from 5.9 to 19.7 nM and is more than 4,000-fold selective for PRMT5/MEP50 over a panel of 20 methyltransferases. GSK3326595 (200 nM) induces alternative splicing of MDM4 in Z-138, MCF-7, JM1, and DOHH-2 cells and increases p53 and p21 protein levels in Z-138 cells in a concentration-dependent manner. GSK3326595 inhibits growth and symmetric dimethyl arginine (SDMA) methylation in several lymphoma and breast cancer cell lines. It also reduces tumor growth in a Z-138 mouse xenograft model when administered at doses of 25, 50, and 100 mg/kg twice per day.Formal Name: 6-[(1-acetyl-4-piperidinyl)amino]-N-[(2S)-3-(3,4-dihydro-2(1H)-isoquinolinyl)-2-hydroxypropyl]-4-pyrimidinecarboxamide. CAS Number: 1616392-22-3. Molecular Formula: C24H32N6O3. Formula Weight: 452.6. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Soluble. lambdamax: 249 nm. SMILES: O=C(C1=CC(NC2CCN(C(C)=O)CC2)=NC=N1)NC[C@H](O)CN3CC4=CC=CC=C4CC3. InChi Code: InChI=1S/C24H32N6O3/c1-17(31)30-10-7-20(8-11-30)28-23-12-22(26-16-27-23)24(33)25-13-21(32)15-29-9-6-18-4-2-3-5-19(18)14-29/h2-5,12,16,20-21,32H,6-11,13-15H2,1H3,(H,25,33)(H,26,27,28)/t21-/m0/s1. InChi Key: JLCCNYVTIWRPIZ-NRFANRHFSA-N.