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

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Inhibitors of Signaling Pathways That Block Reversal of HIV-1 Latency

doi: 10.1128/AAC.01744-18

Figure Lengend Snippet: Kinase inhibitors identified in the screen that blocked the latency-reversing activity of prostratin, panobinostat, or JQ-1 a

Article Snippet: Prostratin, panobinostat, and JQ1 were acquired from Sigma (St. Louis, MO), Selleckchem, and BPS Bioscience (San Diego, CA), respectively.

Techniques: Activity Assay, Inhibition

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Inhibitors of Signaling Pathways That Block Reversal of HIV-1 Latency

doi: 10.1128/AAC.01744-18

Figure Lengend Snippet: Characterization of PF-3758309, danusertib, AZ628, and P276-00 in 24ST1NLESG cells a , b

Article Snippet: Prostratin, panobinostat, and JQ1 were acquired from Sigma (St. Louis, MO), Selleckchem, and BPS Bioscience (San Diego, CA), respectively.

Techniques:

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Inhibitors of Signaling Pathways That Block Reversal of HIV-1 Latency

doi: 10.1128/AAC.01744-18

Figure Lengend Snippet: Characterization of CDK inhibitors in the in 24ST1NLESG cells a

Article Snippet: Prostratin, panobinostat, and JQ1 were acquired from Sigma (St. Louis, MO), Selleckchem, and BPS Bioscience (San Diego, CA), respectively.

Techniques:

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Inhibitors of Signaling Pathways That Block Reversal of HIV-1 Latency

doi: 10.1128/AAC.01744-18

Figure Lengend Snippet: Characterization of mTOR inhibitors in the in 24ST1NLESG cells a

Article Snippet: Prostratin, panobinostat, and JQ1 were acquired from Sigma (St. Louis, MO), Selleckchem, and BPS Bioscience (San Diego, CA), respectively.

Techniques: