SGC0946

DOT1L is a protein methyltransferase (PMT). It is the only enzyme known to methylate histone 3 at lysine 79 (H3K79), where it catalyzes mono-, di-, and trimethylation. Proper DOT1L function is necessary for transcriptional activation of many genes, DNA damage repair, and cell cycle regulation. SGC0946 is a potent inhibitor of DOT1L (IC50 = 0.3 nM) developed by the Structural Genomics Consortium (SGC). It is over 100-fold selective over other PMTs. It is active in cells, reducing H3K79 dimethylation in A431 and MCF10A cells (IC50s = 2.6 and 8.8 nM, respectively). SGC0946 is a brominated analog of EPZ004777, an S-adenosylmethionine-competitive inhibitor of DOT1L. Both SGC0946 and EPZ004777 selectively kill mixed lineage leukemia (MLL) cells, in which DOT1L is aberrantly localized via interaction with an oncogenic MLL fusion protein. The negative control, SGC0649, for SGC0956 is also available exclusively through the SGC. You can submit a request to receive the negative control here.Formal Name: 5-bromo-7-[5-deoxy-5-[[3-[[[[4-(1,1-dimethylethyl)phenyl]amino]carbonyl]amino]propyl](1-methylethyl)amino]-beta-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine. CAS Number: 1561178-17-3. Molecular Formula: C28H40BrN7O4. Formula Weight: 618.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 10 mg/ml, DMSO: 10 mg/ml, Ethanol: 10 mg/ml, Ethanol:PBS (pH 7.2) (1:4): 0.2 mg/ml. lambdamax: 242, 280 nm. SMILES: CC(C)(C)C1=CC=C(NC(NCCCN(C(C)C)C[C@@H]2[C@@H](O)[C@@H](O)[C@H](N3C(N=CN=C4N)=C4C(Br)=C3)O2)=O)C=C1. InChi Code: InChI=1S/C28H40BrN7O4/c1-16(2)35(12-6-11-31-27(39)34-18-9-7-17(8-10-18)28(3,4)5)14-20-22(37)23(38)26(40-20)36-13-19(29)21-24(30)32-15-33-25(21)36/h7-10,13,15-16,20,22-23,26,37-38H,6,11-12,14H2,1-5H3,(H2,30,32,33)(H2,31,34,39)/t20-,22-,23-,26-/m1/s1. InChi Key: IQCKJUKAQJINMK-HUBRGWSESA-N.