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Results: Treatment with 50 to 100 nanomolar (nM) of MLN9708 resulted in time-dependent and dose-dependent cytotoxicity in all cell lines. The IC50 values were 38nM, 52nM, and 41nM for Jurkat, Hut78, and HH, respectively, and 39nM, 60nM, and 117nM for L540, L1236, and L428, respectively. MLN9708 resulted in dose-dependent increase in apoptosis by Annexin-V/PI (p? http://www.selleckchem.com/products/jq1.html with N-acetyl cysteine (NAC) abrogated apoptosis, oxidative stress, and MYC degradation. Additionally, MLN9708 treatment induced several changes in the MAPK signalling pathway. In TCL, it increased pERK and p-p38, whereas pJNK was decreased. Using shRNAs (with MLN9708), ERK and p38 KO had minimal effect in the TCL lines, however JNK KO resulted in increased cell death in Jurkat and Hut78 cells. In HL, ERK and JNK shRNA had minimal effect, whereas p38 KO increased the cytotoxic effect of MLN9708 in all HL cell lines. Finally, in vivo experiments with SCID tumour xenografts showed significant inhibition of tumour growth (p? http://www.selleck.cn/products/AP24534.html as significantly improved survival (p? http://www.selleckchem.com/products/Rapamycin.html HL cell lines and in vivo xenograft models. In all cell lines, MLN9708 down-regulated MYC and cell death was redox-dependent. Further, in TCL, the cytotoxic effect of MLN9708 was mediated through JNK, whereas p38 was the dominant pathway in HL-related cell death. 031 PHARMACOLOGIC INHIBITION OF MALT1 BY DISTINCT PHENOTHIAZINES FOR A TARGET-DIRECTED THERAPY OF ABC-DLBCL D. Nagel,1 S. Spranger,2 M. Vincendeau,1 M. Grau,3 S. Raffegerst,2 B. Kloo,1 D. Hlahla,1 M. Neuenschwander,4 J. von Kries,4 K. Hadian,5 B. Doerken,6 P. Lenz,3 G. Lenz,6 D. J. Schendel,2 D. Krappmann.1 1Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum Muenchen, Neuherberg, Germany; 2Institute of Molecular Immunology, Helmholtz Zentrum Muenchen, Muenchen, Germany; 3Department of Physics, Philipps-University Marburg, Marburg, Germany; 4Screening Unit, Leibniz Institut fuer Molekulare Pharmakologie, Berlin, Germany; 5Assay Development and Screening Platform, Helmholtz Zentrum Muenchen, Neuherberg, Germany; 6Molecular Research Center, Department of Hematology, Oncology and Tumorimmunology, Charite Universitaetsmedizin, Berlin, Germany.