Chaetocin

The methylation of histones by histone methyltransferases (HMT) is an important mechanism by which gene expression is stably altered during cellular differentiation and embryonic development. Chaetocin is a fungal mycotoxin that inhibits the HMT SU(VAR)3-9 (IC50 = 0.8 µM). It inhibits other Lys9-specific HMTs, including G9a (IC50 = 2.5 µM) and DIM5 (IC50 = 3 µM). Selectivity for Lys9-HMTs is indicated by higher IC50 values (>90 µM) for Lys20-specific PRSET7, Lys27-specific EZH2, and Lys4-specific SET7/9. Chaetocin potently induces cellular oxidative stress, selectively killing cancer cells and rapidly-proliferating primary cells. Chaetocin's effects on oxidative stress are, at least in part, due to its capacity to act as a competitive and selective substrate for thioredoxin reductase-1 (Km = 4.6 µM). Chaetocin is useful both in epigenetic studies as an HMT inhibitor and in cancer research.Formal Name: 2,2',3S,3'S,5aR,5'aR,6,6'-octahydro-3,3'-bis(hydroxymethyl)-2,2'-dimethyl-[10bR,10'bR(11aS,11'aS)-bi-3,11a-epidithio-11aH-pyrazino[1',2':1,5]pyrrolo[2,3-b]indole]-1,1',4,4'-tetrone. CAS Number: 28097-03-2. Molecular Formula: C30H28N6O6S4. Formula Weight: 696.8. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMSO: 25 mg/ml. SMILES: O=C1[C@](CO)(SS2)N(C)C([C@]32N1[C@@H](NC4=CC=CC=C45)[C@]5([C@@]6(C7=CC=CC=C7N8)[C@H]8N(C([C@](CO)(SS9)N(C)C%10=O)=O)[C@]%109C6)C3)=O. InChi Code: InChI=1S/C30H28N6O6S4/c1-33-21(39)27-11-25(15-7-3-5-9-17(15)31-19(25)35(27)23(41)29(33,13-37)45-43-27)26-12-28-22(40)34(2)30(14-38,46-44-28)24(42)36(28)20(26)32-18-10-6-4-8-16(18)26/h3-10,19-20,31-32,37-38H,11-14H2,1-2H3/t19-,20-,25+,26+,27+,28+,29+,30+/m1/s1. InChi Key: PZPPOCZWRGNKIR-PNVYSBBASA-N.