Journal: Molecules

Article Title: Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents

doi: 10.3390/molecules20033898

Figure Lengend Snippet: Hydroxamic acid based HDAC inhibitors in clinical trials.

Article Snippet: Molecular dynamics simulations of chemically diverse HDAC inhibitors (SAHA, PCI-34051 and C16) and the HDAC isoforms (8, 10 and 11) of the three different classes of zinc-dependent enzyme were also done [ ].

Techniques: In Vitro

Journal: Molecules

Article Title: Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents

doi: 10.3390/molecules20033898

Figure Lengend Snippet: Benzamide, short chain fatty acid and cyclic peptide based HDAC inhibitors in clinical trials.

Article Snippet: Molecular dynamics simulations of chemically diverse HDAC inhibitors (SAHA, PCI-34051 and C16) and the HDAC isoforms (8, 10 and 11) of the three different classes of zinc-dependent enzyme were also done [ ].

Techniques: In Vitro

Journal: Molecules

Article Title: Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents

doi: 10.3390/molecules20033898

Figure Lengend Snippet: Natural product HDAC inhibitors and their sources.

Article Snippet: Molecular dynamics simulations of chemically diverse HDAC inhibitors (SAHA, PCI-34051 and C16) and the HDAC isoforms (8, 10 and 11) of the three different classes of zinc-dependent enzyme were also done [ ].

Techniques:

Journal: Molecules

Article Title: Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents

doi: 10.3390/molecules20033898

Figure Lengend Snippet: Structures of thioester- and epoxide-based HDAC inhibitors.

Article Snippet: Molecular dynamics simulations of chemically diverse HDAC inhibitors (SAHA, PCI-34051 and C16) and the HDAC isoforms (8, 10 and 11) of the three different classes of zinc-dependent enzyme were also done [ ].

Techniques:

Journal: Molecules

Article Title: Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents

doi: 10.3390/molecules20033898

Figure Lengend Snippet: Structure of representative HDAC inhibitors and their pharmacophores. The cap group, linker and the zinc binding domain (ZBD) are colored green, red and blue, respectively.

Article Snippet: Molecular dynamics simulations of chemically diverse HDAC inhibitors (SAHA, PCI-34051 and C16) and the HDAC isoforms (8, 10 and 11) of the three different classes of zinc-dependent enzyme were also done [ ].

Techniques: Binding Assay

Journal: Molecules

Article Title: Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents

doi: 10.3390/molecules20033898

Figure Lengend Snippet: Multiple anti-tumor pathways activated by HDACi. Extrinsic and intrinsic refer to two apoptosis pathways, and HR and NHEJ refer to two DBS repair pathways.

Article Snippet: Molecular dynamics simulations of chemically diverse HDAC inhibitors (SAHA, PCI-34051 and C16) and the HDAC isoforms (8, 10 and 11) of the three different classes of zinc-dependent enzyme were also done [ ].

Techniques:

Journal: Pharmaceuticals

Article Title: Therapeutic Efficacy of Novel HDAC Inhibitors SPA3052 and SPA3074 against Intestinal Inflammation in a Murine Model of Colitis

doi: 10.3390/ph15121515

Figure Lengend Snippet: DAI score during 14 days of DSS administration in DSS. DAI was counted with the assessment of percentage of weight loss, stool consistency and fecal bleeding; Abbreviations: DAI = disease activity index; CON = control; DSS = dextran sulfate sodium; SAHA = suberoylanilide hydroxamic acid; All data represented mean ± S.E.M; n = 7–12 mice per group; abc Means with different superscripts are significantly different based on the Duncan’s multiple range tests ( p < 0.05).

Article Snippet: The pan-HDAC inhibitor SAHA was purchased from TCI Co. Ltd. (Tokyo Chemical Industry Co., Tokyo, Japan).

Techniques: Activity Assay, Control

Journal: Pharmaceuticals

Article Title: Therapeutic Efficacy of Novel HDAC Inhibitors SPA3052 and SPA3074 against Intestinal Inflammation in a Murine Model of Colitis

doi: 10.3390/ph15121515

Figure Lengend Snippet: Final body weight and colon length.

Article Snippet: The pan-HDAC inhibitor SAHA was purchased from TCI Co. Ltd. (Tokyo Chemical Industry Co., Tokyo, Japan).

Techniques:

Journal: Pharmaceuticals

Article Title: Therapeutic Efficacy of Novel HDAC Inhibitors SPA3052 and SPA3074 against Intestinal Inflammation in a Murine Model of Colitis

doi: 10.3390/ph15121515

Figure Lengend Snippet: Representative images of H&E staining of colon sections. Black arrowheads and red arrowheads indicate leukocytes in mucosa and leukocytes in submucosa, respectively. Red dashed line area indicates loss of surface epithelium black dashed line area indicates mucosa devoid of crypts. Green arrowheads indicate goblet cells. Abbreviations: CON = control; DSS = dextran sulfate sodium; SAHA = suberoylanilide hydroxamic acid.

Article Snippet: The pan-HDAC inhibitor SAHA was purchased from TCI Co. Ltd. (Tokyo Chemical Industry Co., Tokyo, Japan).

Techniques: Staining, Control

Journal: Pharmaceuticals

Article Title: Therapeutic Efficacy of Novel HDAC Inhibitors SPA3052 and SPA3074 against Intestinal Inflammation in a Murine Model of Colitis

doi: 10.3390/ph15121515

Figure Lengend Snippet: Histological scores.

Article Snippet: The pan-HDAC inhibitor SAHA was purchased from TCI Co. Ltd. (Tokyo Chemical Industry Co., Tokyo, Japan).

Techniques:

Journal: Pharmaceuticals

Article Title: Therapeutic Efficacy of Novel HDAC Inhibitors SPA3052 and SPA3074 against Intestinal Inflammation in a Murine Model of Colitis

doi: 10.3390/ph15121515

Figure Lengend Snippet: Protein expression of occludin was measured by Western blot; Abbreviations: CON = control; DSS = dextran sulfate sodium; SAHA = suberoylanilide hydroxamic acid; GAPDH= glyceraldehyde-3-Phosphate dehydrogenase; All data represented mean ± SEM.; n = 7–12 mice per group; ### p < 0.001 compared to the CON group; * p < 0.05 compared to the DSS group.

Article Snippet: The pan-HDAC inhibitor SAHA was purchased from TCI Co. Ltd. (Tokyo Chemical Industry Co., Tokyo, Japan).

Techniques: Expressing, Western Blot, Control

Journal: Pharmaceuticals

Article Title: Therapeutic Efficacy of Novel HDAC Inhibitors SPA3052 and SPA3074 against Intestinal Inflammation in a Murine Model of Colitis

doi: 10.3390/ph15121515

Figure Lengend Snippet: Protein expression of ( a ) SOCS1, ( b ) SOCS3, ( c ) phosphorylated-Akt and Akt, ( d ) phosphorylated-ERK1/2 and ERK1/2, ( e ) phosphorylated-IκBα and IκBα in colon tissue were measured by Western blot; Abbreviations: CON = control; DSS = dextran sulfate sodium; SAHA = suberoylanilide hydroxamic acid; SOCS = suppressor of cytokine signaling; ERK= extracellular signal-regulated kinase; GAPDH = glyceraldehyde-3-Phosphate dehydrogenase; All data represented mean ± S.E.M.; n = 7–12 mice per group; # p < 0.05, ## p < 0.01, ### p < 0.001 compared to the CON group; * p < 0.05, ** p < 0.01 compared to the DSS group.

Article Snippet: The pan-HDAC inhibitor SAHA was purchased from TCI Co. Ltd. (Tokyo Chemical Industry Co., Tokyo, Japan).

Techniques: Expressing, Western Blot, Control

Journal: Pharmaceuticals

Article Title: Therapeutic Efficacy of Novel HDAC Inhibitors SPA3052 and SPA3074 against Intestinal Inflammation in a Murine Model of Colitis

doi: 10.3390/ph15121515

Figure Lengend Snippet: Relative mRNA expressions of IL-4 and IL-13 in colon tissue were measured by real-time PCR analysis; Abbreviations: CON = control; DSS = dextran sulfate sodium; SAHA = suberoylanilide hydroxamic acid; IL = interleukin; GAPDH = glyceraldehyde-3-Phosphate dehydrogenase; All data represented mean ± SEM.; n = 7–12 mice per group; ### p < 0.001 compared to the CON group; * p < 0.05, ** p < 0.01 compared to the DSS group.

Article Snippet: The pan-HDAC inhibitor SAHA was purchased from TCI Co. Ltd. (Tokyo Chemical Industry Co., Tokyo, Japan).

Techniques: Real-time Polymerase Chain Reaction, Control

Journal: Pharmaceuticals

Article Title: Therapeutic Efficacy of Novel HDAC Inhibitors SPA3052 and SPA3074 against Intestinal Inflammation in a Murine Model of Colitis

doi: 10.3390/ph15121515

Figure Lengend Snippet: Chemical structure of the SPA3052 and SPA3074. SPA3052: (Z)-1-phenyl-7-(4-methoxyphenyl)-2,3,7-trithiahepta-4-ene-7-oxide; SPA3074: (Z)-9-(3-Methoxylphenyl)-4,5,9-trithianona-6-ene- 9-oxide; SAHA: suberoylanilide hydroxamic acid.

Article Snippet: The pan-HDAC inhibitor SAHA was purchased from TCI Co. Ltd. (Tokyo Chemical Industry Co., Tokyo, Japan).

Techniques:

Journal: Pharmaceuticals

Article Title: Therapeutic Efficacy of Novel HDAC Inhibitors SPA3052 and SPA3074 against Intestinal Inflammation in a Murine Model of Colitis

doi: 10.3390/ph15121515

Figure Lengend Snippet: Experimental design of the experiments with the administration of SAHA, SPA3052, and SPA3074. Ten weeks old male C57BL/6N mice were used for the experiments. Two cycles of 1.5% DSS administration in performed for colitis induction. Supply of experimental compounds is maintained in the concentration of 50 mg/kg for whole experimental days; n = 7–12 mice per group.

Article Snippet: The pan-HDAC inhibitor SAHA was purchased from TCI Co. Ltd. (Tokyo Chemical Industry Co., Tokyo, Japan).

Techniques: Concentration Assay

Journal: International Journal of Molecular Sciences

Article Title: High-Throughput Screening for CEBPD-Modulating Compounds in THP-1-Derived Reporter Macrophages Identifies Anti-Inflammatory HDAC and BET Inhibitors

doi: 10.3390/ijms22063022

Figure Lengend Snippet: HTS for CEBPD -modulating compounds and identification of hits. ( a ) A schematic drawing of the developed screening assay in THP-1 reporter Mϕ using SEAP reporter. ( b , c ) Here, we show the hit-contained screening plate from the LOPAC ® ( b ) and the hit-containing screening plate from the ENZO ® ( c ) compound libraries. The primary screening data from all plates is summarized in . PMA-differentiated THP-1 reporter Mϕ were not treated (M0), pre-treated with 0.001% ( v / v ) DMSO (solvent control), 10 μM compound from LOPAC ® (b) and ENZO ® (c) libraries, or 0.5 μM TSA for 1 h and stimulated (M1) with 0.1 µg/mL LPS + 20 ng/mL IFN-γ for 24 h for SEAP assay (read 1 and 2). Hit compounds (I-BET151, Ro 11-1464, and SAHA) showing a strong activatory effect on SEAP secretion were identified in areas >3 SDs (m + 3 × SD, black line) of an average signal (m, read line), calculated for the corresponding “M1, DMSO” condition. For read 2, CV was calculated for M0 and M1 DMSO controls (b: 48.9% and 27.7%, respectively; c: 36.6% and 44.4%, respectively). The corresponding Z´-factor was −0.4 (b) and −1.3 (c). RLU: relative luminescence units.

Article Snippet: In conclusion, this study identified the BET inhibitors I-BET151 and Ro 11-1464 as well as the HDAC inhibitors SAHA and TSA from LOPAC ® and ENZO ® libraries as potent CEBPD -modulating compounds in LPS- and IFN-γ-stimulated THP-1 reporter Mφ.

Techniques: Screening Assay, Solvent, Control, SEAP Assay

Journal: International Journal of Molecular Sciences

Article Title: High-Throughput Screening for CEBPD-Modulating Compounds in THP-1-Derived Reporter Macrophages Identifies Anti-Inflammatory HDAC and BET Inhibitors

doi: 10.3390/ijms22063022

Figure Lengend Snippet: The effect of HDAC inhibitors SAHA and TSA on SEAP secretion and mRNA expression. In ( a ), PMA-differentiated THP-1 reporter Mϕ were pre-treated with 10 μM SAHA or 0.5 μM TSA for 1 h and stimulated with 0.1 µg/mL LPS + 20 ng/mL IFN-γ for 24 h for SEAP assay (mean ± SD, n = 3 with 2 wells per condition). Changes in SEAP enzymatic activity were analyzed relative to M1 DMSO control via Brown–Forsythe and Welch ANOVA test with Dunnett’s correction for multiple comparisons; n.s.: not significant; * p < 0.05. In ( b – f ), PMA-differentiated THP-1 reporter Mϕ were pre-treated with 10 μM SAHA or 0.5 μM TSA for 1 h and stimulated with 0.1 µg/mL LPS + 20 ng/mL IFN-γ for 4 h for mRNA expression analysis of reporter CEBPD::SEAP ( b ), endogenous CEBPD ( c ), IL-6 ( d ), CCL2 ( e ), and IL-1ß ( f ) (median and range, n = 3 with 2 wells per condition). mRNA expression analysis was performed via qRT-PCR (ΔΔCt method) using RPL37A as an internal reference gene. Fold change in mRNA expression is displayed relative to M0 control, set as 1. The compound-mediated changes in mRNA expression were analyzed relative to M1 DMSO control via ordinary one-way ANOVA (for normally distributed data and equal SDs), Brown–Forsythe and Welch ANOVA test with Dunnett’s correction (for normally distributed data and different SDs), or Kruskal-Wallis test with Dunn´s correction for multiple comparisons (for non-normally distributed data). * p < 0.05; ** p < 0.005; *** p < 0.001.

Article Snippet: In conclusion, this study identified the BET inhibitors I-BET151 and Ro 11-1464 as well as the HDAC inhibitors SAHA and TSA from LOPAC ® and ENZO ® libraries as potent CEBPD -modulating compounds in LPS- and IFN-γ-stimulated THP-1 reporter Mφ.

Techniques: Expressing, SEAP Assay, Activity Assay, Control, Quantitative RT-PCR

Journal: International Journal of Molecular Sciences

Article Title: High-Throughput Screening for CEBPD-Modulating Compounds in THP-1-Derived Reporter Macrophages Identifies Anti-Inflammatory HDAC and BET Inhibitors

doi: 10.3390/ijms22063022

Figure Lengend Snippet: Fold change (mean ± SD) for mRNA expression in SAHA-pre-treated and TSA-pre-treated target cells compared to M0 controls ( compare Figure 6 ).

Article Snippet: In conclusion, this study identified the BET inhibitors I-BET151 and Ro 11-1464 as well as the HDAC inhibitors SAHA and TSA from LOPAC ® and ENZO ® libraries as potent CEBPD -modulating compounds in LPS- and IFN-γ-stimulated THP-1 reporter Mφ.

Techniques: Expressing