Domain architecture of histone lysine methyltransferases (a, b), protein arginine methyltransferases (c), and histone demethylases (d) of different species

homologs of human proteins (see ) were searched using the Comparative Database from the BROAD Institute (). Corresponding proteins were identified by a search () and domain architectures of proteins were analyzed by the Simple Modular Architecture Research Tool (SMART; ). The number of amino acids of proteins is shown. Accession numbers are given in and .<p><b>Copyright information:</b></p><p>Taken from "Histone modifications and chromatin dynamics: a focus on filamentous fungi"</p><p></p><p>Fems Microbiology Reviews 2008;32(3):409-439.</p><p>Published online 25 Jan 2008</p><p>PMCID:PMC2442719.</p><p>© 2008 The Authors; Journal compilation © 2008 Federation of European Microbiological Societies Published by Blackwell Publishing Ltd</p

Docking results for compounds 8a-8d in HDAC1.

<p>Due to the meta-substitution of the sulfonamide linker the terminal group of the inhibitors is not able to favorably interact with the rim of the pocket. The molecular surface is displayed and contoured according to the hydrophobic potential (magenta = hydrophilic, green = hydrophobic).</p

Compounds 9a-9d inhibit HDAC6 over HDAC1.

<p>Dose response curves of <b>9a-9d</b> comparative inhibition of HDAC6 vs. HDAC1 activity using purified enzymes for in vitro assays measuring deacetylation of histone substrates. Assays were performed in parallel for both enzymes.</p

A, B: <i>9b and 9c strongly alter cell cycle distribution of cancer cells</i>.

<p>HCC4017 lung cancer cells show defects in S-phase progression and accumulation in G2/M after treatment with <b>9b</b> (in A) or <b>9c</b> (in B), as indicated. Cell cycle histograms were collected on PI stained samples of floating and adherent cells, on a FACs Calibur.</p

Induction of GPF and inhibitory activity against partially purified HDAC1.

<p>NS = not soluble,—negative, *The mean values of at least two independent experiments in which duplicate determinations were taken.</p

Differential response of cancers to 9c and 9d.

<p><b>A</b>, GI50 values across the NCI-60 cell line panel in response to <b>9c</b>. <b>B</b>, GI50 values across the NCI-60 cell line panel in response to <b>9d.</b></p

Docking poses of compounds 9a-d in the HDAC6 catalytic domain.

<p>Inhibitors are colored in cyan. The zinc ion is shown as a brown ball. Hydrogen bonds between HDAC6 and inhibitors are shown as blue lines and distances are given in Å. On the right side the molecular surface is displayed and contoured according to the hydrophobic potential (magenta = hydrophilic, green = hydrophobic).</p

1,3,4-Oxadiazole-Containing Histone Deacetylase Inhibitors: Anticancer Activities in Cancer Cells

We describe 1,3,4-oxadiazole-containing hydroxamates (<b>2</b>) and 2-aminoanilides (<b>3</b>) as histone deacetylase inhibitors. Among them, <b>2t</b>, <b>2x</b>, and <b>3i</b> were the most potent and selective against HDAC1. In U937 leukemia cells, <b>2t</b> was more potent than SAHA in inducing apoptosis, and <b>3i</b> displayed cell differentiation with a potency similar to MS-275. In several acute myeloid leukemia (AML) cell lines, as well as in U937 cells in combination with doxorubicin, <b>3i</b> showed higher antiproliferative effects than SAHA