DS-437

DS-437 is a dual inhibitor of protein arginine methyltransferase 5 (PRMT5) and PRMT7 (IC50s = 5.9 and 6 µM, respectively). It is selective for PRMT5 and PRMT7 over a panel of 29 additional protein, DNA, and RNA methyltransferases at 50 µM, but also inhibits DNMT3A and DNMT3B (IC50s = 52 and 62 µM, respectively). DS-437 (2.5 and 10 µM) inhibits symmetrical arginine dimethylation of FOXP3 in HEK293T cells, as well as symmetrical arginine dimethylation of p60 and the ribonucleoproteins SmD1/D3 and SmB/B' in MDA-MB-231 cells in a concentration-dependent manner. It inhibits the ability of regulatory T cells (Tregs) to suppress effector T cell (Teff) proliferation in vitro in human and murine Treg suppression assays. DS-437 (10 mg/kg five times per week) reduces tumor growth in a CT26Her2 murine colon cancer model when administered in combination with the anti-p185erbB2/neu antibody 4D5.Formal Name: 5'-S-[2-[[(ethylamino)carbonyl]amino]ethyl]-5'-thio-adenosine. CAS Number: 1674364-87-4. Molecular Formula: C15H23N7O4S. Formula Weight: 397.5. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: soluble. SMILES: O=C(NCC)NCCSC[C@@H]1[C@@H](O)[C@@H](O)[C@@](N2C3=NC=NC(N)=C3N=C2)([H])O1. InChi Code: InChI=1S/C15H23N7O4S/c1-2-17-15(25)18-3-4-27-5-8-10(23)11(24)14(26-8)22-7-21-9-12(16)19-6-20-13(9)22/h6-8,10-11,14,23-24H,2-5H2,1H3,(H2,16,19,20)(H2,17,18,25)/t8-,10-,11-,14-/m1/s1. InChi Key: CACMCLIHCDTJHL-IDTAVKCVSA-N.