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Protein arginine methyltransferases (PRMTs) target nuclear and cytoplasmic substrates and can alter protein actions and gene expression. PRMT5, which can methylate histones H2A, H3, and H4, ribonucleoproteins, and other proteins, is upregulated in several human cancers, including lymphomas. Moreover, suppression of PRMT5 expression induces lymphoma cell death. EPZ015666 is a potent, orally bioavailable inhibitor of PRMT5 (Ki = 5 nM). It displays more than 20,000-fold selectivity for PRMT5 over other PMTs. EPZ015666 acts by blocking the association of PRMT5 with methylosome protein 50, which is necessary for the formation of an active methyltransferase complex. EPZ015666 (100 mg/kg twice daily) blocks the growth of mantle cell lymphoma Z-138 xenografts, without significant body weight loss, in mice.Formal Name: N-[(2S)-3-(3,4-dihydro-2(1H)-isoquinolinyl)-2-hydroxypropyl]-6-(3-oxetanylamino)-4-pyrimidinecarboxamide. CAS Number: 1616391-65-1. Synonyms: GSK3235025. Molecular Formula: C20H25N5O3. Formula Weight: 383.4. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml, Ethanol: 10 mg/ml. lambdamax: 246, 304 nm. SMILES: O=C(NC[C@H](O)CN1CCC(C=CC=C2)=C2C1)C3=CC(NC4COC4)=NC=N3. InChi Code: InChI=1S/C20H25N5O3/c26-17(10-25-6-5-14-3-1-2-4-15(14)9-25)8-21-20(27)18-7-19(23-13-22-18)24-16-11-28-12-16/h1-4,7,13,16-17,26H,5-6,8-12H2,(H,21,27)(H,22,23,24)/t17-/m0/s1. InChi Key: ZKXZLIFRWWKZRY-KRWDZBQOSA-N.
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