PLASMA PHARMACOKINETICS AND METABOLISM OF THE HISTONE DEACETYLASE INHIBITOR TRICHOSTATIN A AFTER INTRAPERITONEAL ADMINISTRATION TO MICE

Sanderson, L.; Taylor, G.W.; Aboagye, E.O.; Alao, J.P.; Latigo, J.R.; Coombes, R.C.; Vigushin, D.M.

doi:10.1124/dmd.104.000638

Cited by 95Histone Deacetylase Inhibitors ResearchPharmacogenetics and Drug MetabolismAnalytical Methods in Pharmaceuticals

PLASMA PHARMACOKINETICS AND METABOLISM OF THE HISTONE DEACETYLASE INHIBITOR TRICHOSTATIN A AFTER INTRAPERITONEAL ADMINISTRATION TO MICE

Sanderson, L., Taylor, G.W., Aboagye, E.O., Alao, J.P., Latigo, J.R., Coombes, R.C., Vigushin, D.M.·2004·Drug Metabolism and Disposition

DOI 10.1124/dmd.104.000638

Open this paper in CoChat — free account

Abstract

Trichostatin A is a potent and specific histone deacetylase inhibitor with promising antitumor activity in preclinical models. Plasma pharmacokinetics of trichostatin A were studied following single-dose intraperitoneal administration of 80 mg/kg (high dose) or 0.5 mg/kg (low dose) to female BALB/c mice. Plasma trichostatin A concentrations were quantified by high performance liquid chromatography (HPLC)-UV assay (high dose) or by HPLC-multiple reaction monitoring assay (low dose). Trichostatin A was rapidly absorbed from the peritoneum and detectable in plasma within 2 min. Cmax of 40 microg/ml and 8 ng/ml occurred within 5 min, followed by rapid exponential decay in plasma trichostatin A concentration with t1/2 of 6.3 min and 9.6 min (high and low doses, respectively). Phase I metabolites at the high dose were identified by simultaneous UV and positive ion electrospray mass spectrometry. Trichostatin A underwent extensive metabolism: primary metabolic pathways were N-demethylation, reduction of the hydroxamic acid to the corresponding trichostatin A amide, and oxidative deamination to trichostatic acid. N-Monomethyl trichostatin A amide was the major plasma metabolite. No didemethylated compounds were identified. Trichostatic acid underwent further biotransformation: reduction and beta-oxidation of the carboxylic acid, with or without N-demethylation, resulted in formation of dihydro trichostatic acid and dinor dihydro trichostatic acids. HPLC fractions corresponding to trichostatin A and N-demethylated trichostatin A exhibited histone deacetylase-inhibitory activity; no other fractions were biologically active. We conclude that trichostatin A is rapidly and extensively metabolized in vivo following intraperitoneal administration to mice, and N-demethylation does not compromise histone deacetylase-inhibitory activity.

Integrity signals

Registry

Crossref · 10.1124/dmd.104.000638

Cites

30 of 30 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

The short half-life of TSA does not make it a good candidate for in vivo use.
“The short half-life of TSA does not make it a good candidate for in vivo use (42), but more stable and more specific KDAC inhibitors have been developed and are contemplated for application in anticancer therapy (43, 44).”
From Identification of a Key Lysine Residue in Heat Shock Protein 90 Required for Azole and Echinocandin Resistance in Aspergillus fumigatus (2014) · cites this paper as [42]

Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A.
Yoshida, M., Kijima, M., Akita, M., & Beppu, T. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44885-x · Cited by 1,856 · see citing works
Histone acetylation and transcriptional regulatory mechanisms
Struhl, K. (1998) · Genes & Development · doi:10.1101/gad.12.5.599 · Cited by 1,815 · see citing works
Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors
Finnin, M. S., Donigian, J. R., Cohen, A., Richon, V. M., Rifkind, R. A., Marks, P. A., Breslow, R., & Pavletich, N. P. (1999) · Nature · doi:10.1038/43710 · Cited by 1,714 · see citing works
Histone Deacetylase Inhibitors: Inducers of Differentiation or Apoptosis of Transformed Cells
Marks, P. A., Richon, V. M., & Rifkind, R. A. (2000) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/92.15.1210 · Cited by 1,152 · see citing works
Role of the histone deacetylase complex in acute promyelocytic leukaemia
Lin, R. J., Nagy, L., Inoue, S., Shao, W., Miller, W. H., & Evans, R. M. (1998) · Nature · doi:10.1038/35895 · Cited by 1,060 · see citing works
What's Up and Down with Histone Deacetylation and Transcription?
Pazin, M. J., & Kadonaga, J. T. (1997) · Cell · doi:10.1016/s0092-8674(00)80211-1 · Cited by 820 · see citing works
Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes
Kim, M. S., Kwon, H. J., Lee, Y. M., Baek, J. H., Jang, J.-E., Lee, S.-W., Moon, E.-J., Kim, H.-S., Lee, S., Chung, H. Y., et al. (2001) · Nature Medicine · doi:10.1038/86507 · Cited by 732 · see citing works
Histone acetylases and deacetylases in cell proliferation
Kouzarides, T. (1999) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)80006-9 · Cited by 602 · see citing works
Histone acetylation: chromatin in action
Wade, P. A., Pruss, D., & Wolffe, A. P. (1997) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(97)01016-5 · Cited by 468 · see citing works
Trichostatin A is a histone deacetylase inhibitor with potent antitumor activity against breast cancer in vivo.
Vigushin, D. M., Ali, S., Pace, P., Mirsaidi, N., Ito, K., Adcock, I. M., & Coombes, R. C. (2001) · PubMed · Cited by 439 · see citing works
Self-citation
Histone deacetylase inhibitors modulate renal disease in the MRL-lpr/lpr mouse
Mishra, N., Reilly, C. M., Brown, D. R., Ruiz, P., & Gilkeson, G. S. (2003) · Journal of Clinical Investigation · doi:10.1172/jci16153 · Cited by 405 · see citing works
A new antifungal antibiotic, trichostatin.
Tsuji, N., Kobayashi, M., NAGASHIMA, K., Wakisaka, Y., & Koizumi, K. (1976) · The Journal of Antibiotics · doi:10.7164/antibiotics.29.1 · Cited by 341 · see citing works
Cardiac hypertrophy and histone deacetylase–dependent transcriptional repression mediated by the atypical homeodomain protein Hop
Kook, H., Lepore, J. J., Gitler, A. D., Lu, M. M., Yung, W. W.-M., Mackay, J. P., Zhou, R., Ferrari, V. A., Gruber, P. J., & Epstein, J. A. (2003) · Journal of Clinical Investigation · doi:10.1172/jci19137 · Cited by 332 · see citing works
Sinful repression
Wolffe, A. P. (1997) · Nature · doi:10.1038/387016a0 · Cited by 282 · see citing works
A decline in the levels of progesterone receptor coactivators in the pregnant uterus at term may antagonize progesterone receptor function and contribute to the initiation of parturition
Condon, J. C., Jeyasuria, P., Faust, J. M., Wilson, J. W., & Mendelson, C. R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1633616100 · Cited by 270 · see citing works
Triple post‐transcriptional control
Bechhofer, D. H. (1990) · Molecular Microbiology · doi:10.1111/j.1365-2958.1990.tb02051.x · Cited by 204 · see citing works
Effects of trichostatins on differentiation of murine erythroleukemia cells.
Yoshida, M., Nomura, S., & Beppu, T. (1987) · PubMed · Cited by 171 · see citing works
Histone deacetylase inhibitors are the potent inducer/enhancer of differentiation in acute myeloid leukemia: a new approach to anti-leukemia therapy.
Kosugi, H., Towatari, M., Hatano, S., Kitamura, K., Kiyoi, H., Kinoshita, T., Tanimoto, M., Murate, T., Kawashima, K., Saito, H., et al. (1999) · Leukemia · doi:10.1038/sj.leu.2401508 · Cited by 150 · see citing works
Histone deacetylase inhibitors as potential anti-skin cancer agents.
Saunders, N. A., Dicker, T., Popa, C., Jones, S. J. M., & Dahler, A. L. (1999) · PubMed · Cited by 137 · see citing works
Human mesenchymal stem cells support megakaryocyte and pro-platelet formation from CD34+ hematopoietic progenitor cells
Cheng, L., Qasba, P., Vanguri, P., & Thiede, M. A. (2000) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(200007)184:1 · Cited by 136 · see citing works
Structural specificity for biological activity of trichostatin a, a specific inhibitor of mammalian cell cycle with potent differentiation-inducing activity in friend leukemia cells.
Yoshida, M., Hoshikawa, Y., Koseki, K., Mori, K., & Beppu, T. (1990) · The Journal of Antibiotics · doi:10.7164/antibiotics.43.1101 · Cited by 101 · see citing works
Targeted Histone Deacetylase Inhibition for Cancer Therapy
Vigushin, D. M., & Coombes, R. C. (2004) · Current Cancer Drug Targets · doi:10.2174/1568009043481560 · Cited by 93 · see citing works
Self-citation
Major Phase I Biotransformation Pathways of Trichostatin A in Rat Hepatocytes and in Rat and Human Liver Microsomes
Elaut, G., Török, G., Vinken, M., Laus, G., Papeleu, P., Tourwé, D. A., & Rogiers, V. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.12.1320 · Cited by 47 · see citing works
Trichostatin C, a glucopyranosyl hydroxamate.
TSUJI, N., & Kobayashi, M. (1978) · The Journal of Antibiotics · doi:10.7164/antibiotics.31.939 · Cited by 43 · see citing works
Cardiac hypertrophy and histone deacetylase–dependent transcriptional repression mediated by the atypical homeodomain protein Hop
Kook, H., Lepore, J. J., Gitler, A. D., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319137 · Cited by 39 · see citing works
Histone deacetylase inhibitors modulate renal disease in the MRL-lpr/lpr mouse
Mishra, N., Reilly, C. M., Brown, D. R., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200316153 · Cited by 29 · see citing works
Histone acetylation and the control of the cell cycle
Magnaghi-Jaulin, L., Ait‐Si‐Ali, S., & Harel‐Bellan, A. (2000) · Springer eBooks · doi:10.1007/978-1-4615-4253-7_4 · Cited by 26 · see citing works
Properties of chicken erythrocyte histone deacetylase associated with the nuclear matrix
Li, W., Chen, H. Y., & Davie, J. (1996) · Biochemical Journal · doi:10.1042/bj3140631 · Cited by 26 · see citing works
Stereodefined and polyunsaturated inhibitors of histone deacetylase based on (2E,4E)-5-arylpenta-2,4-dienoic acid hydroxyamides
Marson, C. M., Serradji, N., Rioja, A. S., Gastaud, S. P., Alao, J. P., Coombes, R. C., & Vigushin, D. M. (2004) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2004.03.012 · Cited by 17 · see citing works
Self-citation
Effect of in vivo Histone Hyperacetylation on the State of Chromatin Fibers
Krajewski, W. A. (1999) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.1999.10508318 · Cited by 11 · see citing works

Flagged first, then by citations

Sorted by citations

Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy
Avila, A. M., Burnett, B. G., Taye, A. A., Gabanella, F., Knight, M. A., Hartenstein, P., Cizman, Z., Prospero, N. A. D., Pellizzoni, L., Fischbeck, K. H., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29562 · Cited by 350 · see citing works
Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects.
Myzak, M. C., Tong, P. S. L., Dashwood, W., Dashwood, R. H., & Ho, E. (2007) · PubMed · doi:10.3181/00379727-207-2320227 · Cited by 312 · see citing works
The Rebirth of Matrix Metalloproteinase Inhibitors: Moving Beyond the Dogma
Fields, G. B. (2019) · Cells · doi:10.3390/cells8090984 · Cited by 304 · see citing works
Epigenetic targeting of histone deacetylase: Therapeutic potential in Parkinson's disease?
Harrison, I. F., & Dexter, D. T. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.05.010 · Cited by 227 · see citing works
Class I Histone Deacetylase Inhibitor Entinostat Suppresses Regulatory T Cells and Enhances Immunotherapies in Renal and Prostate Cancer Models
Shen, L., Ciesielski, M. J., Ramakrishnan, S., Miles, K. M., Ellis, L., Sotomayor, P. C., Shrikant, P. A., Fenstermaker, R. A., & Пили, Р. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030815 · Cited by 205 · see citing works
Epigenetic Control of Sexual Differentiation of the Bed Nucleus of the Stria Terminalis
Murray, E. K., Hien, A., Vries, G. J. D., & Forger, N. G. (2009) · Endocrinology · doi:10.1210/en.2009-0458 · Cited by 166 · see citing works
Histone deacetylase inhibition attenuates diabetes-associated kidney growth: potential role for epigenetic modification of the epidermal growth factor receptor
Gilbert, R. E., Huang, Q., Thai, K., Advani, S. L., Lee, K., Yuen, D. A., Connelly, K. A., & Advani, A. (2011) · Kidney International · doi:10.1038/ki.2011.39 · Cited by 124 · see citing works
Importance of epigenetic mechanisms in visceral pain induced by chronic water avoidance stress
Tran, L., Chaloner, A., Sawalha, A. H., & van-Meerveld, B. G. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.09.016 · Cited by 124 · see citing works
Inhibition of histone deacetylase activity on specific embryonic tissues as a new mechanism for teratogenicity
Menegola, E., Renzo, F. D., Broccia, M. L., Prudenziati, M., Minucci, S., Massa, V., & Giavini, E. (2005) · Birth Defects Research Part B Developmental and Reproductive Toxicology · doi:10.1002/bdrb.20053 · Cited by 123 · see citing works
Epigenetic regulation of immune escape genes in cancer
Tomasi, T. B., Magner, W. J., & Khan, A. N. H. (2006) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-006-0164-4 · Cited by 117 · see citing works
Inhibition of histone deacetylase in utero causes sociability deficits in postnatal mice
Moldrich, R. X., Leanage, G., She, D. T., Dolan‐Evans, E., Nelson, M., Reza, N., & Reutens, D. C. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.09.049 · Cited by 111 · see citing works
HDAC inhibitors in experimental liver and kidney fibrosis
Beneden, K. V., Mannaerts, I., Pauwels, M., Branden, C. V. D., & van Grunsven, L. A. (2013) · Fibrogenesis & Tissue Repair · doi:10.1186/1755-1536-6-1 · Cited by 109 · see citing works
Hydroxamates: Relationships between Structure and Plasma Stability
Flipo, M., Charton, J., Hocine, A., Dassonneville, S., Deprez, B. P., & Deprez-Poulain, R. F. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm900648x · Cited by 105 · see citing works
The histone deacetylase inhibitor trichostatin A upregulates regulatory T cells and modulates autoimmunity in NZB/W F1 mice
Reilly, C. M., Thomas, M. R., Gogal, R. M., Olgun, S., Santo, A., Sodhi, R., Samy, E. T., Peng, S. L., Gilkeson, G. S., & Mishra, N. (2008) · Journal of Autoimmunity · doi:10.1016/j.jaut.2008.04.020 · Cited by 99 · see citing works
Histone deacetylase inhibitors (HDACIs). Structure—activity relationships: history and new QSAR perspectives
Pontiki, E. A., & Hadjipavlou‐Litina, D. (2010) · Medicinal Research Reviews · doi:10.1002/med.20200 · Cited by 89 · see citing works
Antimalarial Activity of the Anticancer Histone Deacetylase Inhibitor SB939
Sumanadasa, S. D. M., Goodman, C. D., Lucke, A. J., Skinner‐Adams, T. S., Sahama, I., Haque, A., Do, T. A., McFadden, G. I., Fairlie, D. P., & Andrews, K. T. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00030-12 · Cited by 86 · see citing works
Histone Deacetylase Inhibitors through Click Chemistry
Shen, J., Woodward, R., Kedenburg, J., Liu, X., Chen, M., Fang, L., Sun, D., & Wang, P. G. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm8005355 · Cited by 85 · see citing works
Metabolism as a key to histone deacetylase inhibition
Rajendran, P., Williams, D. E., Ho, E., & Dashwood, R. H. (2011) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2011.557713 · Cited by 75 · see citing works
Identification of a Key Lysine Residue in Heat Shock Protein 90 Required for Azole and Echinocandin Resistance in Aspergillus fumigatus
Lamoth, F., Juvvadi, P. R., Soderblom, E. J., Moseley, M. A., Asfaw, Y. G., & Steinbach, W. J. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02286-13 · Cited by 74 · see citing works
Hydroxamate, a Key Pharmacophore Exhibiting a Wide Range of Biological Activities
Bertrand, S., Hélesbeux, J., Larcher, G., & Duval, O. (2013) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/13895575113139990007 · Cited by 66 · see citing works
Coordination Chemistry Based Approach to Lipophilic Inhibitors of 1-Deoxy- d -xylulose-5-phosphate Reductoisomerase
Deng, L., Sundriyal, S., Rubio, V., Shi, Z.-Z., & Song, Y. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm9012592 · Cited by 65 · see citing works
Energy Metabolism in H460 Lung Cancer Cells: Effects of Histone Deacetylase Inhibitors
Amoêdo, N. D., Rodrigues, M. F., Pezzuto, P., Galina, A., da Costa, R. M., Almeida, F. C. L., El‐Bacha, T., & Rumjanek, F. D. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022264 · Cited by 61 · see citing works
Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis
Lamoth, F., Juvvadi, P. R., & Steinbach, W. J. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.00096 · Cited by 61 · see citing works
Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis
Beneden, K. V., Geers, C., Pauwels, M., Mannaerts, I., Wissing, K. M., Branden, C. V. D., & van Grunsven, L. A. (2013) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2013.05.013 · Cited by 58 · see citing works
Heat shock protein 90 (Hsp90): A novel antifungal target against Aspergillus fumigatus
Lamoth, F., Juvvadi, P. R., & Steinbach, W. J. (2014) · Critical Reviews in Microbiology · doi:10.3109/1040841x.2014.947239 · Cited by 57 · see citing works
Enhanced drug delivery to the reproductive tract using nanomedicine reveals therapeutic options for prevention of preterm birth
Zierden, H. C., Ortiz, J., DeLong, K., Yu, J., Li, G., Dimitrion, P. M., Bensouda, S., Laney, V. E. A., Bailey, A. M., Anders, N. M., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abc6245 · Cited by 56 · see citing works
Epigenetic Regulator CoREST Controls Social Behavior in Ants
Glastad, K. M., Graham, R. J., Ju, L., Roessler, J. M., Brady, C. M., & Berger, S. L. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.10.012 · Cited by 56 · see citing works
Selective inhibition of histone deacetylase 3 by novel hydrazide based small molecules as therapeutic intervention for the treatment of cancer
Pulya, S., Patel, T. K., Paul, M., Adhikari, N., Banerjee, S., Routholla, G., Biswas, S., Jha, T., & Ghosh, B. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114470 · Cited by 55 · see citing works
The pan HDAC inhibitor Givinostat improves muscle function and histological parameters in two Duchenne muscular dystrophy murine models expressing different haplotypes of the LTBP4 gene
Licandro, S. A., Crippa, L., Pomarico, R., Perego, R., Fossati, G., Leoni, F., & Steinkühler, C. (2021) · Skeletal Muscle · doi:10.1186/s13395-021-00273-6 · Cited by 50 · see citing works
Targeting histone deacetylases for the treatment of disease
Lawless, M. W., Norris, S., O'Byrne, K. J., & Gray, S. G. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00571.x · Cited by 49 · see citing works
Histone Deacetylase Inhibitors: A Therapeutic Key in Neurological Disorders?
Ziemka‐Nałęcz, M., Jaworska, J., Sypecka, J., & Zalewska, T. (2018) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nly073 · Cited by 50 · see citing works
Targeted deletion of NF-κB p50 diminishes the cardioprotection of histone deacetylase inhibition
Zhang, L., Zhao, Y., Cheng, G., Guo, T. L., Chin, Y. E., Liu, P. Y., & Zhao, T. (2010) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01015.2009 · Cited by 49 · see citing works
Antifungal Activity of Compounds Targeting the Hsp90‐Calcineurin Pathway Against Various Mould Species
Lamoth, F., Alexander, B. D., Juvvadi, P. R., & Steinbach, W. J. (2015) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dku549 · Cited by 47 · see citing works
Biocompatible Boron-Containing Prodrugs of Belinostat for the Potential Treatment of Solid Tumors
Zheng, S., Guo, S., Zhong, Q., Zhang, C., Liu, J., Yang, L., Zhang, Q., & Wang, G. (2018) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.7b00504 · Cited by 45 · see citing works
Histone deacetylase regulation of immune gene expression in tumor cells
Khan, A. N. H., & Tomasi, T. B. (2007) · Immunologic Research · doi:10.1007/s12026-007-0085-0 · Cited by 45 · see citing works
In Vivo Application of Histone Deacetylase Inhibitor Trichostatin‐A Impairs Murine Male Meiosis
Fenic, I., Hossain, H., Sonnack, V., Tchatalbachev, S., Thierer, F., Trapp, J., Failing, K., Edler, K. S., Bergmann, M., Jung, M., et al. (2008) · Journal of Andrology · doi:10.2164/jandrol.107.003848 · Cited by 44 · see citing works
Epigenetics in Liver Fibrosis: Could HDACs be a Therapeutic Target?
Clavería-Cabello, A., Colyn, L., Arechederra, M., Urmán, J., Berasain, C., Avila, M. A., & Fernández‐Barrena, M. G. (2020) · Cells · doi:10.3390/cells9102321 · Cited by 43 · see citing works
Increased uptake of [123I]meta-iodobenzylguanidine, [18F]fluorodopamine, and [3H]norepinephrine in mouse pheochromocytoma cells and tumors after treatment with the histone deacetylase inhibitors
Martiniova, L., Perera, S. M., Brouwers, F. M., Alesci, S., Abu-Asab, M. S., Marvelle, A. F., Kiesewetter, D. O., Thomasson, D. M., Morris, J. C., Květňanský, R., et al. (2010) · Endocrine Related Cancer · doi:10.1677/erc-10-0090 · Cited by 43 · see citing works
Transcriptional regulation of cholesterol 24-hydroxylase by histone deacetylase inhibitors
Shafaati, M., O’Driscoll, R., Björkhem, I., & Meaney, S. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.11.103 · Cited by 42 · see citing works
Effect of serum triiodothyronine on regulation of cardiac gene expression: role of histone acetylation
Danzi, S. E., Dubon, P., & Klein, I. L. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00182.2005 · Cited by 39 · see citing works
HDAC Dependent Transcriptional Repression of Bmp-7 Potentiates TGF-β Mediated Renal Fibrosis in Obstructive Uropathy
Manson, S. R., Song, J. B., Hruska, K. A., & Austin, P. F. (2013) · The Journal of Urology · doi:10.1016/j.juro.2013.06.110 · Cited by 37 · see citing works
Dynamic changes in histone deacetylases following kidney ischemia-reperfusion injury are critical for promoting proximal tubule proliferation
Hyndman, K. A., Kasztan, M., Mendoza, L. D., & Monteiro‐Pai, S. (2019) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00499.2018 · Cited by 33 · see citing works
A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy
Han, L., Wang, T., Wu, J., Yin, X., Fang, H., & Zhang, N. (2016) · International Journal of Nanomedicine · doi:10.2147/ijn.s118727 · Cited by 32 · see citing works
High-throughput identification of post-transcriptional utrophin up-regulators for Duchenne muscle dystrophy (DMD) therapy
Loro, E., Sengupta, K., Bogdanovich, S., Whig, K., Schultz, D., Huryn, D. M., & Khurana, T. S. (2020) · Scientific Reports · doi:10.1038/s41598-020-58737-6 · Cited by 31 · see citing works
Histone deacetylase in neuropathology
Gupta, R. V., Ambasta, R. K., & Kumar, P. (2020) · Advances in clinical chemistry · doi:10.1016/bs.acc.2020.09.004 · Cited by 28 · see citing works
Discovery and Mechanism of Natural Products as Modulators of Histone Acetylation
Salvador, L. A., & Luesch, H. (2012) · Current Drug Targets · doi:10.2174/138945012802008973 · Cited by 29 · see citing works
A Metabolic Screening Study of Trichostatin A (TSA) and TSA-Like Histone Deacetylase Inhibitors in Rat and Human Primary Hepatocyte Cultures
Elaut, G., Laus, G., Alexandre, E., Richert, L., Bachellier, P., Tourwé, D., Rogiers, V., & Vanhaecke, T. (2007) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.116202 · Cited by 26 · see citing works
Non-hydroxamate inhibitors of 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR): A critical review and future perspective
Kesharwani, S., & Sundriyal, S. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.113055 · Cited by 26 · see citing works
Inhibition of NF‐κB activation by the histone deacetylase inhibitor 4‐Me2N‐BAVAH induces an early G1 cell cycle arrest in primary hepatocytes
Papeleu, P., Wullaert, A., Elaut, G., Henkens, T., Vinken, M., Laus, G., Tourwé, D. A., Beyaert, R., Rogiers, V., & Vanhaecke, T. (2007) · Cell Proliferation · doi:10.1111/j.1365-2184.2007.00466.x · Cited by 23 · see citing works
Pharmacokinetics and metabolism of UK-383,367 in rats and dogs: A rationale for long-lived plasma radioactivity
Allan, G. A., Gedge, J. I., Nedderman, A. N. R., Roffey, S. J., Small, H. F., & Webster, R. (2006) · Xenobiotica · doi:10.1080/00498250600618177 · Cited by 22 · see citing works
A selenium-containing selective histone deacetylase 6 inhibitor for targeted in vivo breast tumor imaging and therapy
Tang, C. C., Du, Y., Liang, Q. Y., Cheng, Z., & Tian, J. (2019) · Journal of Materials Chemistry B · doi:10.1039/c9tb00383e · Cited by 20 · see citing works
Pharmacokinetics of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol and its active metabolite after oral and intravenous administration in rat
Zhang, X., Xu, J., Zhang, D., Gu, J., & Zhao, Y. (2009) · Xenobiotica · doi:10.1080/00498250902810951 · Cited by 20 · see citing works
Histone acetylation determines transcription of atypical protein kinases in rat neurons
Borodinova, A. A., Ma, K., Alekseeva, V. S., & Balaban, P. M. (2019) · Scientific Reports · doi:10.1038/s41598-019-40823-z · Cited by 19 · see citing works
Development of a Novel Ferrocenyl Histone Deacetylase Inhibitor for Triple-Negative Breast Cancer Therapy
Tang, C. C., Du, Y., Liang, Q. Y., Cheng, Z., & Tian, J. (2018) · Organometallics · doi:10.1021/acs.organomet.8b00354 · Cited by 18 · see citing works
Pharmacokinetic studies with PET
Bergström, M., & Långström, B. (2005) · Birkhäuser-Verlag eBooks · doi:10.1007/3-7643-7426-8_8 · Cited by 17 · see citing works
Synthetic Fosmidomycin Analogues with Altered Chelating Moieties Do Not Inhibit 1-Deoxy-D-xylulose 5-phosphate Reductoisomerase or Plasmodium falciparum Growth In Vitro
Chofor, R., Risseeuw, M., Pouyez, J., Johny, C., Wouters, J., Dowd, C. S., Couch, R. D., & Calenbergh, S. V. (2014) · Molecules · doi:10.3390/molecules19022571 · Cited by 17 · see citing works
In silico structure-based discovery of a SARS-CoV-2 main protease inhibitor
Wen, L., Tang, K., Chik, K. K., Chan, C. C.-Y., Tsang, J. O., Liang, R., Cao, J., Huang, Y., Luo, C., Cai, J., et al. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.59191 · Cited by 16 · see citing works
Histone modification–mediated epigenetic regulation in AKI-to-CKD transition: a cell-type-specific perspective
Chai, S., Zeng, Z., Shang, J., Xu, Y., Han, X., Ma, B., Lv, Z., & Wang, R. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-07350-0 · Cited by 14 · see citing works
Inhibition of the HIF-1 Survival Pathway as a Strategy to Augment Photodynamic Therapy Efficacy
de Keijzer, M. J., de Klerk, D. J., de Haan, L. R., van Kooten, R. T., Franchi, L. P., Dias, L. M., Kleijn, T. G., van Doorn, D. J., Heger, M., & on behalf of the Photodynamic Therapy Study Group (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2099-1_19 · Cited by 12 · see citing works
Trichostatin A blocks aldosterone‐induced Na+ transport and control of serum‐ and glucocorticoid‐inducible kinase 1 in cortical collecting duct cells
Mansley, M. K., Roe, A. J., Francis, S. L., Gill, J. H., Bailey, M. A., & Wilson, S. M. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14837 · Cited by 11 · see citing works
Histone deacetylase inhibition abolishes stress-induced spatial memory impairment
Vargas-López, V., Lamprea, M. R., & Múnera, A. (2016) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2016.08.009 · Cited by 11 · see citing works
Simple inhibitors of histone deacetylase activity that combine features of short-chain fatty acid and hydroxamic acid inhibitors
Tischler, J. L., Abuaita, B. H., Cuthpert, S. C., Fage, C. D., Murphy, K., Saxe, A., Furr, E. B., Hedrick, J., Meyers, J., Snare, D. J., et al. (2008) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756360701715703 · Cited by 11 · see citing works
Suberoylanilide hydroxamic acid suppresses hepatic stellate cells activation by HMGB1 dependent reduction of NF-κB1
Wang, W., Yan, M., Ji, Q., Lu, J., Ji, Y., & Ji, J. (2015) · PeerJ · doi:10.7717/peerj.1362 · Cited by 11 · see citing works
Contribution of Epigenetic Modifications to the Decline in Transgene Expression from Plasmid DNA in Mouse Liver
Zang, L., Nishikawa, M., Ando, M., Takahashi, Y., & Takakura, Y. (2015) · Pharmaceutics · doi:10.3390/pharmaceutics7030199 · Cited by 9 · see citing works
Nephrotoxicity of epigenetic inhibitors used for the treatment of cancer
Scholpa, N. E., Kolli, R. T., Moore, M., Arnold, R. D., Glenn, T. C., & Cummings, B. S. (2016) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2016.08.010 · Cited by 9 · see citing works
HDAC Inhibitors and Other Histone Modifying Natural Products as Emerging Anticancer Agents
Salvador, L. A., & Luesch, H. (2012) · Springer eBooks · doi:10.1007/978-1-4614-4654-5_4 · Cited by 7 · see citing works
HDAC inhibition leads to age-dependent opposite regenerative effect upon PTEN deletion in rubrospinal axons after SCI
Seira, O., Wang, W., Lee, S. C. L., Roskams, J., & Tetzlaff, W. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.02.006 · Cited by 7 · see citing works
Recent Insights Into Mechanism and Structure of MEP Pathway Enzymes and Implications for Inhibition Strategies
DeColli, A. A., Johnston, M. L., & Meyers, C. L. F. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.14710-9 · Cited by 6 · see citing works
Differential effects of HDAC inhibitors on PPN oscillatory activity in vivo
Bisagno, V., Bernardi, A., Blasco, S. S., Urbano, F. J., & García‐Rill, E. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107922 · Cited by 6 · see citing works
Ulleunganilines A–C, Trichostatin Analogues Bearing a Modified Side Chain from Streptomyces sp. 13F051
Hwang, G. J., Jang, M., Son, S., Lee, B., Jang, J., Lee, J., Ko, S., Hong, Y., Ahn, J. S., & Jang, J. (2021) · Journal of Natural Products · doi:10.1021/acs.jnatprod.1c00324 · Cited by 5 · see citing works
Trichostatin A
Beljanski, V. (2009) · xPharm: The Comprehensive Pharmacology Reference · doi:10.1016/b978-008055232-3.64490-3 · Cited by 4 · see citing works
Treatment of Status Epilepticus after Traumatic Brain Injury Using an Antiseizure Drug Combined with a Tissue Recovery Enhancer Revealed by Systems Biology
Kajevu, N., Lipponen, A., Andrade, P., Bañuelos‐Cabrera, I., Puhakka, N., Hämäläinen, E., Natunen, T., Hiltunen, M. O., & Pitkänen, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241814049 · Cited by 3 · see citing works
Total synthesis of the HDAC inhibitor (+)-( R )-trichostatin A via O -directed dialkylacetylene free radical hydrostannation with Ph 3 SnH/Et 3 B. The unusual inhibitory effect of a proximal α-OPv group on the course of a vinyl iodide Stille cross-coupling
Pan, K., Manaviazar, S., & Hale, K. J. (2025) · Organic & Biomolecular Chemistry · doi:10.1039/d4ob01848f · Cited by 3 · see citing works
Scaffold dependent histone deacetylase (HDAC) inhibitor induced re-equilibration of the subcellular localization and post-translational modification state of class I HDACs
Hanigan, T. W., Taha, T. Y., Aboukhatwa, S. M., Frasor, J. M., & Petukhov, P. A. (2017) · PLoS ONE · doi:10.1371/journal.pone.0186620 · Cited by 3 · see citing works
A NOVEL VALIDATED UHPLC METHOD FOR ESTIMATION OF ASSAY AND ITS RELATED SUBSTANCES OF TRICHOSTATIN-A
Rao, L. V., RAO, K. T., & Kandepi, V. V. K. M. (2020) · International Journal of Pharmacy and Pharmaceutical Sciences · doi:10.22159/ijpps.2020v12i7.37198 · Cited by 3 · see citing works
Non‐Hydroxamate Inhibitors of IspC Enzyme in the MEP Pathway: Structural Insights and Drug Development Potential
Zhou, Y., Wang, J., Sun, Y., Cheng, Y., & Wu, W. (2025) · Chemical Biology & Drug Design · doi:10.1111/cbdd.70086 · Cited by 2 · see citing works
Development of a D-μSPE method based on curcumin-modified magnetic reduced graphene oxide nanocomposite for the determination of Trichostatin A in a biological sample
Ghanbari, A., Es’haghi, Z., Khoshnood, R. S., & Beyramabadi, S. A. (2021) · International Journal of Environmental & Analytical Chemistry · doi:10.1080/03067319.2021.1897120 · Cited by 2 · see citing works
Upregulation of MHC I antigen processing machinery gene expression in breast cancer cells by Trichostatin A
Murtadha, A. H., Sharudin, N. A., Azahar, I. I. M., Has, A. T. C., & Mokhtar, N. F. (2024) · Molecular Biology · doi:10.31857/s0026898424010105 · Cited by 1 · see citing works
Upregulation of MHC I Antigen Processing Machinery Gene Expression in Breast Cancer Cells by Trichostatin A
Murtadha, A. H., Sharudin, N. A., Azahar, I. I. M., Has, A. T. C., & Mokhtar, N. F. (2023) · Molecular Biology · doi:10.1134/s0026893324010151 · Cited by 1 · see citing works
24s-Hydroxycholesterol. Studies on regulatory mechanisms behind its formation in the brain and its potential use as a marker for neurodegeneration
Shafaati, M. (2010) · Figshare
Estabelecimento e caracterização de modelo xenotransplantável de mastocitoma canino para estudo de antineoplásicos
Nagamine, M. K. (2011) · doi:10.11606/t.10.2011.tde-25062012-091331
Role of HDAC inhibition and environmental condition in altering phases of amphetamine self-administration
Arndt, D. L. (2016) · K-State Research Exchange (Kansas State University)
Additional file 8 of The pan HDAC inhibitor Givinostat improves muscle function and histological parameters in two Duchenne muscular dystrophy murine models expressing different haplotypes of the LTBP4 gene
Licandro, S. A., Crippa, L., Pomarico, R., Perego, R., Fossati, G., Leoni, F., & Steinkühler, C. (2021) · Figshare · doi:10.6084/m9.figshare.15041218
Additional file 4 of The pan HDAC inhibitor Givinostat improves muscle function and histological parameters in two Duchenne muscular dystrophy murine models expressing different haplotypes of the LTBP4 gene
Licandro, S. A., Crippa, L., Pomarico, R., Perego, R., Fossati, G., Leoni, F., & Steinkühler, C. (2021) · Figshare · doi:10.6084/m9.figshare.15041206
Additional file 5 of The pan HDAC inhibitor Givinostat improves muscle function and histological parameters in two Duchenne muscular dystrophy murine models expressing different haplotypes of the LTBP4 gene
Licandro, S. A., Crippa, L., Pomarico, R., Perego, R., Fossati, G., Leoni, F., & Steinkühler, C. (2021) · Figshare · doi:10.6084/m9.figshare.15041209
Additional file 2 of The pan HDAC inhibitor Givinostat improves muscle function and histological parameters in two Duchenne muscular dystrophy murine models expressing different haplotypes of the LTBP4 gene
Licandro, S. A., Crippa, L., Pomarico, R., Perego, R., Fossati, G., Leoni, F., & Steinkühler, C. (2021) · Figshare · doi:10.6084/m9.figshare.15041200
Additional file 1 of The pan HDAC inhibitor Givinostat improves muscle function and histological parameters in two Duchenne muscular dystrophy murine models expressing different haplotypes of the LTBP4 gene
Licandro, S. A., Crippa, L., Pomarico, R., Perego, R., Fossati, G., Leoni, F., & Steinkühler, C. (2021) · Figshare · doi:10.6084/m9.figshare.15041197
Additional file 6 of The pan HDAC inhibitor Givinostat improves muscle function and histological parameters in two Duchenne muscular dystrophy murine models expressing different haplotypes of the LTBP4 gene
Licandro, S. A., Crippa, L., Pomarico, R., Perego, R., Fossati, G., Leoni, F., & Steinkühler, C. (2021) · Figshare · doi:10.6084/m9.figshare.15041212
Additional file 3 of The pan HDAC inhibitor Givinostat improves muscle function and histological parameters in two Duchenne muscular dystrophy murine models expressing different haplotypes of the LTBP4 gene
Licandro, S. A., Crippa, L., Pomarico, R., Perego, R., Fossati, G., Leoni, F., & Steinkühler, C. (2021) · Figshare · doi:10.6084/m9.figshare.15041203
Additional file 7 of The pan HDAC inhibitor Givinostat improves muscle function and histological parameters in two Duchenne muscular dystrophy murine models expressing different haplotypes of the LTBP4 gene
Licandro, S. A., Crippa, L., Pomarico, R., Perego, R., Fossati, G., Leoni, F., & Steinkühler, C. (2021) · Figshare · doi:10.6084/m9.figshare.15041215
BindingDB Entry 50018219: Non-hydroxamate inhibitors of 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR): A critical review and future perspective.
BindingDB (2024) · UC San Diego · doi:10.7270/q2417288
BindingDB Entry 50027635: Histone deacetylase inhibitors through click chemistry.
BindingDB (2010) · UC San Diego · doi:10.7270/q20p0zv9
BindingDB Entry 50002942: Biocompatible Boron-Containing Prodrugs of Belinostat for the Potential Treatment of Solid Tumors.
BindingDB (2020) · UC San Diego · doi:10.7270/q2s75k03
BindingDB Entry 50014614: Ulleunganilines A-C, Trichostatin Analogues Bearing a Modified Side Chain from
BindingDB (2022) · UC San Diego · doi:10.7270/q24x5cmp
BindingDB Entry 50016088: Selective inhibition of histone deacetylase 3 by novel hydrazide based small molecules as therapeutic intervention for the treatment of cancer.
BindingDB (2023) · UC San Diego · doi:10.7270/q2fn1b6d

Major Phase I Biotransformation Pathways of Trichostatin A in Rat Hepatocytes and in Rat and Human Liver Microsomes
Elaut, G., Török, G., Vinken, M., Laus, G., Papeleu, P., Tourwé, D. A., & Rogiers, V. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.12.1320 · Cited by 47 · see citing works
[Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A].
Yoshida, M. (2007) · PubMed · Cited by 19 · see citing works
2007a) A metabolic screening study of Trichostatin A (TSA) and TSA-like histone deacetylase inhibitors in rat and human primary hepatocyte cultures
Elaut, G., Laus, G., Alex, E., Richert, L., Bachellier, P., Rogiers, V., & Vanhaecke, T. (2016)
A Metabolic Screening Study of Trichostatin A (TSA) and TSA-Like Histone Deacetylase Inhibitors in Rat and Human Primary Hepatocyte Cultures
Elaut, G., Laus, G., Alexandre, E., Richert, L., Bachellier, P., Tourwé, D., Rogiers, V., & Vanhaecke, T. (2007) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.116202 · Cited by 26 · see citing works
284 Benzamide-based trichostatin a analogues are potent and metabolically stable inhibitors of histone deacetylase
Elaut, G., Laus, G., Papeleu, P., Breckx, V., hemel, J. V., Sola, M. E. I., Brosch, G., Snykers, S., Vanhaecke, T., Tourwé, D. A., et al. (2003) · Toxicology Letters · doi:10.1016/s0378-4274(03)90283-9

Authors: Sanderson, L., Taylor, G. W., Aboagye, E. O., Alao, J. P., Latigo, J. R., Coombes, R. C., & Vigushin, D. M.
Affiliations: Hammersmith Hospital (GB)
Imperial College London (GB)
ORCID: Taylor, G.W.
Aboagye, E.O.
Alao, J.P.
Coombes, R.C.
Venue: Drug Metabolism and Disposition
Publisher: Elsevier BV
Published: 2004-10
Volume: 32
Issue: 10
Pages: 1132-1138
ISSN: 0090-9556 (ISSN-L)
DOI: 10.1124/dmd.104.000638
OpenAlex: W2107542208
Cited by: 90
References: 28
Citations by year: 2025: 3 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 13 · 2020: 6 · 2019: 8 · 2018: 3 · 2017: 1 · 2016: 4 · 2015: 4 · 2014: 3 · 2013: 6 · 2012: 5
FWCI: 1.18
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Drug Metabolism and Disposition (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
Keywords: trichostatin A, histone deacetylase inhibitors, plasma pharmacokinetics, drug metabolism, intraperitoneal administration, N-demethylation, oxidative deamination, fatty acid beta-oxidation, anticancer agents, BALB/c mice
MeSH terms: Animals, Chromatography, High Pressure Liquid, Enzyme Inhibitors, Female, Histone Deacetylases, Hydroxamic Acids, Injections, Intraperitoneal, Mice, Inbred BALB C, Rats, Wistar, Mice, Rats, Histone Deacetylase Inhibitors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

PLASMA PHARMACOKINETICS AND METABOLISM OF THE HISTONE DEACETYLASE INHIBITOR TRICHOSTATIN A AFTER INTRAPERITONEAL ADMINISTRATION TO MICE

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks