Anti-Histone H3 monoclonal antibody, clone O308/13

Histone lysine N-methyltransferase 2D (KMT2D), an important methyltransferase that is involved in the methylation of lysine 4 in histone H3 (H3K4) and related to the development of prostate cancer. Hypermethylation of H3K4 is shown in prostate cancer (PCa). However, KMT2D inhibitors have not yet been developed. This article aims to design small molecule inhibitors targeting KMT2D_SET to prevent PCa cell proliferation and migration. Twenty-four inhibitors were firstly designed according to a virtual screening of computers, and shown different degrees of binding to KMT2D_SET. Compounds 1 and 16 showed high binding affinities to KMT2D, with KD values of 147 +/- 32.9 mu M and 176 +/- 37.9 mu M, respectively. In addition, they exerted strong inhibitory activity against the PCa cell lines PC-3 and DU145, with IC50 values of 1.1 +/- 0.06 mu M, 1.5 +/- 0.06 mu M and 1.8 +/- 0.1 mu M, 2.3 +/- 0.2 mu M, respectively. Furthermore, these two compounds significantly suppressed the migration of PCa cells. (C) 2020 Elsevier Inc. All rights reserved.

The phytotoxicities of TBECH diastereomers to plants at the biochemical and molecular levels were investigated in a hydroponic study by using maize as a model plant. The results showed that TBECH could induce the production of two species of reactive oxygen species (ROS), O-2(center dot-) and H2O2, in maize tissues. The accumulation of ROS was the highest when maize was exposed to beta-TBECH. TBECH enhanced the phosphorylation of plant histone, and the contents of gamma-H2AX in maize followed the order beta-TBECH > alpha beta-TBECH > gamma delta-TBECH > gamma-TBECH. Transcriptome profiling revealed that antioxidant enzyme genes (AEGs) were over-expressed in maize when stressed by technical grade TBECH. The RT-PCR detection further validated that three typical AEGs, including CAT, SOD, and POD genes, were time-dependent and selectively expressed under the influence of TBECH diastereomers. Molecular compositions of maize root exudates characterized by FT-ICR-MS were significantly different among the four groups of TBECH diastereomer treatments. TBECH diastereomers specifically affected the chemical diversity and abundance of root exudates. New insights into the biochemical effects of TBECH on plants are provided in this work, which is helpful to deepening the understanding of their stereo-selectivity. (C) 2020 Elsevier B.V. All rights reserved.