Journal: Neuromolecular medicine

Article Title: The Effect of Histone Deacetylase Inhibitors Panobinostat or Entinostat on Motor Recovery in Mice After Ischemic Stroke

doi: 10.1007/s12017-021-08647-1

Figure Lengend Snippet: Schematic representation of the study design. Pano 3.0 3 mg/kg panobinostat; Pano 10.0 10 mg/kg panobinostat; Entino 1.7 1.7 mg/kg entinostat; Entino 5.0 5.0 mg/kg entinostat; R randomization

Article Snippet: Panobinostat and entinostat (products P180500 and E559300, Toronto Research Chemicals) were administered intraperitoneally at 5 ml/kg volume ( Al Shoyaib et al. 2019 ), every other day (~ 3 h before the dark cycle started), starting from post-stroke day 5 to 15.

Techniques:

Journal: Neuromolecular medicine

Article Title: The Effect of Histone Deacetylase Inhibitors Panobinostat or Entinostat on Motor Recovery in Mice After Ischemic Stroke

doi: 10.1007/s12017-021-08647-1

Figure Lengend Snippet: Panobinostat or entinostat does not substantially affect the number of inhibitory interneurons in ipsilateral AGm. Top left panel, panobinostat- or entinostat-treated mice have comparable number of parvalbumin-positive (PV+) neurons in ipsilateral (I) and contralateral (C) medial premotor area (AGm, medial agranular cortex) (n = 6 per group; p > 0.05 for I vs. C comparisons within each experimental group). Top right panel, comparable number of DAPI-stained nuclei was documented within the same subareas of AGm in experimental groups. Bottom panel, a representative immunofluorescence confocal microscopy image of a mouse brain section on day 42 after stroke. PV signal is depicted in green and cell nuclei (stained with DAPI) in blue. Note that the representative Cresyl violet-stained brain section is shown to illustrate the imaged medial premotor area (red boxes). Pano 3.0 3 mg/kg panobinostat; Pano 10.0 10 mg/kg panobinostat; Entino 1.7 1.7 mg/kg entinostat; Entino 5.0 5.0 mg/kg entinostat

Article Snippet: Panobinostat and entinostat (products P180500 and E559300, Toronto Research Chemicals) were administered intraperitoneally at 5 ml/kg volume ( Al Shoyaib et al. 2019 ), every other day (~ 3 h before the dark cycle started), starting from post-stroke day 5 to 15.

Techniques: Staining, Immunofluorescence, Confocal Microscopy

Journal: Neuromolecular medicine

Article Title: The Effect of Histone Deacetylase Inhibitors Panobinostat or Entinostat on Motor Recovery in Mice After Ischemic Stroke

doi: 10.1007/s12017-021-08647-1

Figure Lengend Snippet: Voluntary running distance and speed. Daily running distance (panel a) and total average running (panel b) of mice in experimental groups. Mice treated with panobinostat and entinostat covered similar distance of running compared to vehicle-treated animals. Panel c, speed of running in experimental groups did not differ significantly during the last three weeks of the study. Panel d, compared to their baseline body weight values, sham and stroke (sp = 0.032 and 0.0016, respectively) and 5 mg/kg entinostat-treated animals (ep = 0.025) gained 2–2.5 g weight by completion of the study. Vehicle and 1.7 mg/kg entinostat-treated animals (vp = 0.014 and ep < 0.001, respectively) lost ~ 2 g during the same period. N = 12/group in all panels; Pano 3.0 3 mg/kg panobinostat; Pano 10.0 10 mg/kg panobinostat; Entino 1.7 1.7 mg/kg entinostat; Entino 5.0 5.0 mg/kg entinostat

Article Snippet: Panobinostat and entinostat (products P180500 and E559300, Toronto Research Chemicals) were administered intraperitoneally at 5 ml/kg volume ( Al Shoyaib et al. 2019 ), every other day (~ 3 h before the dark cycle started), starting from post-stroke day 5 to 15.

Techniques:

Journal: Neuromolecular medicine

Article Title: The Effect of Histone Deacetylase Inhibitors Panobinostat or Entinostat on Motor Recovery in Mice After Ischemic Stroke

doi: 10.1007/s12017-021-08647-1

Figure Lengend Snippet: Lack of effect on motor recovery with panobinostat or entinostat treatment in grid-walking test. Panels a and b, following photothrombotic stroke mice treated with different doses of panobinostat or entinostat did not exhibit improvement in the affected forelimb motor function (i.e., number of footfaults; **p < 0.001 for sham vs. vehicle within day comparisons, n = 12/group). Panel c, no functional deficit was observed in the unaffected (i.e., ipsilateral) forepaw of mice in experimental groups (p > 0.05 for all within group and within day comparisons). Pano 3.0 3 mg/kg panobinostat; Pano 10.0 10 mg/kg panobinostat; Entino 1.7 1.7 mg/kg entinostat; Entino 5.0 5.0 mg/kg entinostat

Article Snippet: Panobinostat and entinostat (products P180500 and E559300, Toronto Research Chemicals) were administered intraperitoneally at 5 ml/kg volume ( Al Shoyaib et al. 2019 ), every other day (~ 3 h before the dark cycle started), starting from post-stroke day 5 to 15.

Techniques: Functional Assay

Journal: Neuromolecular medicine

Article Title: The Effect of Histone Deacetylase Inhibitors Panobinostat or Entinostat on Motor Recovery in Mice After Ischemic Stroke

doi: 10.1007/s12017-021-08647-1

Figure Lengend Snippet: Unaffected motor recovery with panobinostat or entinostat treatment in cylinder test. Panels a and b, the affected forelimb motor function of mice treated with panobinostat or entinostat was similar to that of vehicle-treated animals after photothrombotic stroke (**p < 0.001 for sham vs. vehicle within day comparisons; n = 12/group). Pano 3.0 3 mg/kg panobinostat; Pano 10.0 10 mg/kg panobinostat; Entino 1.7 1.7 mg/kg entinostat; Entino 5.0 5.0 mg/kg entinostat

Article Snippet: Panobinostat and entinostat (products P180500 and E559300, Toronto Research Chemicals) were administered intraperitoneally at 5 ml/kg volume ( Al Shoyaib et al. 2019 ), every other day (~ 3 h before the dark cycle started), starting from post-stroke day 5 to 15.

Techniques:

Journal: Neuromolecular medicine

Article Title: The Effect of Histone Deacetylase Inhibitors Panobinostat or Entinostat on Motor Recovery in Mice After Ischemic Stroke

doi: 10.1007/s12017-021-08647-1

Figure Lengend Snippet: Infarct location and volume. Left panel, volumetric assessment of brain infarction did not reveal statistically significant differences among experimental groups on day 42 after stroke (n = 6 per group; p > 0.05, vehicle vs. other groups). Right panel, a representative Cresyl Violet-stained mouse brain on day 42 after stroke, indicating location of infarction in the primary motor cortex. Pano 3.0 3 mg/kg panobinostat; Pano 10.0 10 mg/kg panobinostat; Entino 1.7 1.7 mg/kg entinostat; Entino 5.0 5.0 mg/kg entinostat

Article Snippet: Panobinostat and entinostat (products P180500 and E559300, Toronto Research Chemicals) were administered intraperitoneally at 5 ml/kg volume ( Al Shoyaib et al. 2019 ), every other day (~ 3 h before the dark cycle started), starting from post-stroke day 5 to 15.

Techniques: Staining

Journal: Neuromolecular medicine

Article Title: The Effect of Histone Deacetylase Inhibitors Panobinostat or Entinostat on Motor Recovery in Mice After Ischemic Stroke

doi: 10.1007/s12017-021-08647-1

Figure Lengend Snippet: Inhibition of brain histone deacetylases after peripheral administration of panobinostat or entinostat. Following photothrombotic stroke, mice were treated with panobinostat (3, 10 and 30 mg/kg) or entinostat (1.7, 5 and 15 mg/kg) every other day starting on post-stroke day 5 and one day after the last dosing animals were euthanized to obtain the peri-infarct cortical tissue (post-stroke day 16) for Western Blotting. Left and right panels, representative immunoblotting experiments documenting acetylation status of histone 3 after panobinostat (left panel) or entinostat (right panel) treatments. Pano 3.0 3 mg/kg panobinostat; Pano 10.0 10 mg/kg panobinostat; Pano 30.0 30 mg/kg panobinostat; Entino 1.7 1.7 mg/kg entinostat; Entino 5.0 5.0 mg/kg entinostat; Entino 15.0 15 mg/kg entinostat

Article Snippet: Panobinostat and entinostat (products P180500 and E559300, Toronto Research Chemicals) were administered intraperitoneally at 5 ml/kg volume ( Al Shoyaib et al. 2019 ), every other day (~ 3 h before the dark cycle started), starting from post-stroke day 5 to 15.

Techniques: Inhibition, Western Blot

Journal: EBioMedicine

Article Title: Multiply spliced HIV RNA is a predictive measure of virus production ex vivo and in vivo following reversal of HIV latency

doi: 10.1016/j.ebiom.2021.103241

Figure Lengend Snippet: Detection of MS RNA is associated with detection of plasma HIV RNA following administration of the HDACi panobinostat to PLWH on ART. (a) US, MS, and plasma HIV were measured and the percentage of participants positive for each RNA measure are shown for timepoints prior to panobinostat and ( b ) on panobinostat treatment. ( c ) The proportion of participants with a positive plasma HIV RNA according to the amount of MS RNA. ( d ) Amount of MS RNA in samples collected at time points prior to and following panobinostat where plasma HIV RNA was detected or not . For d, data are shown as median +/- IQR. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001 .

Article Snippet: For the prospective panobinostat clinical trial, HIV RNA was normalized to the 18s housekeeping gene using the 18s Taqman gene Expression Assay (Life Technologies, cat # 4331182) and HIV RNA is presented as copies per 10^6 18s copies, as previously described.

Techniques: Clinical Proteomics

Journal: EBioMedicine

Article Title: Multiply spliced HIV RNA is a predictive measure of virus production ex vivo and in vivo following reversal of HIV latency

doi: 10.1016/j.ebiom.2021.103241

Figure Lengend Snippet: Correlation between SN RNA and either US or MS RNA 3 days post-stimulation with LRAs. ( a ) Spearman correlation coefficients and 95% confidence intervals are shown for comparisons between SN RNA and US or MS RNA in total and resting CD4+ T cells after adjustment for repeated measures from the same donor using raw and fold change data following stimulation with LRAs. ( b ) Scatter plots are shown for the fold change from DMSO and the raw values of each parameter quantified in total (closed) and resting (open) CD4+ T cells. The Spearman correlation coefficients (r) and p values after controlling for multiple observations per donor are shown. Each donor is shown as a different symbol and each LRA a different color. Gray = DMSO, blue = vorinostat, purple = romidepsin, green = panobinostat, orange = JQ1, PMA+PHA = red. * p < 0.05; ** p < 0.01; *** p < 0.001, **** p < 0.0001.

Article Snippet: For the prospective panobinostat clinical trial, HIV RNA was normalized to the 18s housekeeping gene using the 18s Taqman gene Expression Assay (Life Technologies, cat # 4331182) and HIV RNA is presented as copies per 10^6 18s copies, as previously described.

Techniques:

Journal: The EMBO Journal

Article Title: HDAC6-dependent deacetylation of SAE2 enhances SUMO1 conjugation for mitotic integrity

doi: 10.1038/s44318-025-00532-y

Figure Lengend Snippet: ( A ) Western blot, representative of three, of acetyl-K164-SAE2 (mouse monoclonal) following anti-FLAG immunoprecipitation from U2OS cells and U2OS cells expressing FLAG-SAE2 in unsynchronised cells or cells treated with nocodazole for 17 h before washing and releasing into mitosis for 10 min. HDAC inhibitors, Panobinostat (HDAC class I, II, and IV), ACY-738 (HDAC6), and RGFP966 (HDAC3), were applied to cells in the last 2 h of nocodazole synchronisation at 2.5 µM and reapplied upon the release. An antibody specific for phosphorylated-Ser10 on histone 3 is used as a marker of mitosis. Quantification of the relative abundance of acetyl-K164-SAE2 relative to the total abundance of SAE2 immunoprecipitated. Error bars = SEM; N = 3 biological repeats. *** P < 0.001, ** P < 0.01, * P < 0.05, ns = not significant P > 0.05. Vehicle vs Nocodazole P = 0.0002, Nocodazole vs Pan-HDACi P = 0.0143, Nocodazole vs HDAC6i P = 0.0019, Nocodazole vs HDAC3i P = 0.9494. Statistical significance was calculated using one-way ANOVA. ( B ) Western blot analysis of a FLAG-SAE2 co-immunoprecipitation with HDAC6 from U2OS, in the context of an asynchronous cell population or following a 16 h nocodazole-treatment and mitotic shake-off. Replicated twice in the laboratory. ( C ) Western blot of acK164-SAE2 following anti-FLAG immunoprecipitation from U2OS cells and U2OS cells expressing FLAG-SAE2 in asynchronous cells treated with indicated combinations of inhibitors against the histone acetyltransferases p300 (A-485), TIP60 (NU9056), NAT10 (Remodelin Hydrobromide), and GCN5 (Butyrolactone). Inhibitors were added for 2 h at 2.5 µM. Replicated three times in the laboratory.

Article Snippet: Panobinostat , SignalChem , H83-904G.

Techniques: Western Blot, Immunoprecipitation, Expressing, Marker

Journal: Cancer chemotherapy and pharmacology

Article Title: Panobinostat penetrates the blood–brain barrier and achieves effective brain concentrations in a murine model

doi: 10.1007/s00280-021-04313-2

Figure Lengend Snippet: Pharmacokinetic experimental design. The figure provides an overview of drug administration and subsequent experimental steps of this study. Twelve mice were administered 15 mg/kg panobinostat intravenously at time-point 0. Three mice from each treatment group were killed at each time-point of 1, 2, 4, and 7 h after injection. Once killed, brain tissue and plasma samples were obtained, processed and analyzed by liquid chromatography–mass spectroscopy to determine drug concentrations, and then analyzed for pharmacokinetic parameters. Figure created with BioRender.com. Abbreviations: TVI tail vein injection, LC–MS liquid chromatography–mass spectroscopy, PK pharmacokinetic

Article Snippet: Panobinostat [2-hydroxypropanoic acid, compound with 2-(E)-Nhydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl] amino]methyl] phenyl]-2-propenamide] was purchased from Cayman Chemical Company (Ann Arbor, MI, USA).

Techniques: Injection, Liquid Chromatography, Mass Spectrometry, Liquid Chromatography with Mass Spectroscopy

Journal: Cancer chemotherapy and pharmacology

Article Title: Panobinostat penetrates the blood–brain barrier and achieves effective brain concentrations in a murine model

doi: 10.1007/s00280-021-04313-2

Figure Lengend Snippet: Pharmacokinetic profile of panobinostat. Pharmacokinetic profile of panobinostat in brain and plasma. a Time–concentration curve of panobinostat concentrations in brain and plasma. Mean concentrations (ng/mL) of panobinostat in the plasma (circle) were 27.3 ± 2.5 at 1 h, 7.56 ± 1.8 at 2 h, 1.48 ± 0.56 at 4 h, and 2.33 ± 1.18 at 7h. Mean concentrations (ng/g) of panobinostat in the brain (square) were 60.5 ± 6.1 at 1 h, 42.9 ± 5.4 at 2 h, 33.2 ± 6.1 at 4 h, and 28.1 ± 4.3 at 7 h. b Brain:Plasma concentration ratios of panobinostat over time. Ratios of brain panobinostat concentration to plasma panobinostat concentration were 2.22 at 1 h, 5.67 at 2 h, 22.43 at 4 h, and 12.06 at 7 h. c Plasma and brain area under the curve (AUC) profile for panobinostat in plasma and brain. The AUC from hour 1 to hour 7 of plasma (black) was 95.0 h.ng/mL and brain (gray) was 250 h.ng/g. d Observed and model predicted (median) plasma and brain concentrations of panobinostat in mice. The estimated Cmax in plasma and brain with a 15 mg/kg IV dose is 131.7 ng/mL and 72.4 ng/g, respectively. Figures created with GraphPad Prism. Abbreviations: Cmax = maximum concentration, IV intravenous

Article Snippet: Panobinostat [2-hydroxypropanoic acid, compound with 2-(E)-Nhydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl] amino]methyl] phenyl]-2-propenamide] was purchased from Cayman Chemical Company (Ann Arbor, MI, USA).

Techniques: Concentration Assay