Chemical phylogenetics of histone deacetylases
Open accessAbstract
The broad study of histone deacetylases in chemistry, biology and medicine relies on tool compounds to derive mechanistic insights. A phylogenetic analysis of Class I and II HDACs as targets of a comprehensive, structurally diverse panel of inhibitors revealed unexpected isoform selectivity even among compounds widely perceived as non-selective. The synthesis and study of a focused library of cinnamic hydroxamates allowed the identification of a first non-selective HDAC inhibitor. These data will guide a more informed use of HDAC inhibitors as chemical probes and therapeutic agents.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Benzamide-containing HDACi possess greater isoform selectivity profiles, targeting specifically only the class I subgroup of HDACs.
“They have also been demonstrated to possess greater isoform selectivity profiles, targeting specifically only the class I subgroup of HDACs (6-10, 26, 38, 39).”
From Histone Deacetylase (HDAC) Inhibitor Kinetic Rate Constants Correlate with Cellular Histone Acetylation but Not Transcription and Cell Viability (2013) · cites this paper as [26]
The Results identify MS-275, CI-994 and MGDC-0103 as benzamide-based inhibitors; the Discussion reports extraordinary selectivity of this inhibitor type for HDAC1, HDAC2 and HDAC3 over the other enzymes discussed. But the claim’s “only” is stronger than the evidence: the Comparative Study says HDAC10 and HDAC11 could not be assayed, so the paper does not establish exclusivity across all HDAC isoforms. No page numbers were provided in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSAHA and TSA selectivity profiles extended well beyond HDAC1 and HDAC2.
“but their selectivity profiles extended well beyond these isoforms as reported previously (12, 13, 26, 29, 30, 38).”
From Histone Deacetylase (HDAC) Inhibitor Kinetic Rate Constants Correlate with Cellular Histone Acetylation but Not Transcription and Cell Viability (2013) · cites this paper as [26]
Previous reports postulate that an intramolecular hydrogen bond between the amine and carbonyl must be broken to permit successful zinc chelation, and a desolvation penalty is paid for this rearrangement.
“This is consistent with previous reports postulating that an intramolecular hydrogen bond between the amine and carbonyl must be broken to permit successful zinc chelation, and a desolvation penalty is paid for this rearrangement to occur (1, 25-28, 34).”
From Histone Deacetylase (HDAC) Inhibitor Kinetic Rate Constants Correlate with Cellular Histone Acetylation but Not Transcription and Cell Viability (2013) · cites this paper as [26]
The Discussion describes zinc chelation and a hydrogen bond between an HDAC active-site residue and a hydroxamate carbonyl, but not an intramolecular bond between an amine and carbonyl. Searches for that bond and for a desolvation penalty found no passage addressing either proposed step; page numbers are unavailable in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredClass IIa enzymes, HDAC3, HDAC8, and HDAC11 removed the non-physiological Ktfa substrate.
“Class IIa enzymes (Lahm et al., 2007) as well as HDAC3 (Madsen and Olsen, 2012a), HDAC8 (Bradner et al., 2010), and HDAC11 (Inks et al., 2012) removed the physiologically non-relevant trifluoroacetamide (Ktfa).”
From Histone deacetylase 11 is an ε-N-Myristoyllysine hydrolase (2018) · cites this paper as Bradner et al., 2010
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform
Katoh, K. (2002) · Nucleic Acids Research · doi:10.1093/nar/gkf436 · Cited by 17,027 · see citing works
A Rapid Bootstrap Algorithm for the RAxML Web Servers
Stamatakis, A., Hoover, P., & Rougemont, J. (2008) · Systematic Biology · doi:10.1080/10635150802429642 · Cited by 7,028 · see citing works
MAFFT version 5: improvement in accuracy of multiple sequence alignment
Katoh, K., Kuma, K., Toh, H., & Miyata, T. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki198 · Cited by 5,063 · see citing works
Lysine acetylation targets protein complexes and co-regulates major cellular functions
Choudhary, C., Kumar, C., Gnad, F., Nielsen, M. L., Rehman, M., Walther, T. C., Olsen, J. V., & Mann, M. (2009) · Science · doi:10.1126/science.1175371 · Cited by 4,040 · see citing works
Recent developments in the MAFFT multiple sequence alignment program
Katoh, K., & Toh, H. (2008) · Briefings Bioinform. · doi:10.1093/bib/bbn013 · Cited by 3,707 · see citing works
Anticancer activities of histone deacetylase inhibitors
Bolden, J. E., Peart, M. J., & Johnstone, R. W. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2133 · Cited by 2,919 · see citing works
Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer
Minucci, S., & Pelicci, P. G. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1779 · Cited by 2,211 · see citing works
Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action
Tsankova, N. M., Berton, O., Renthal, W., Kumar, A., Neve, R. L., & Nestler, E. J. (2006) · Nature Neuroscience · doi:10.1038/nn1659 · Cited by 1,780 · see citing works
Gregoretti, I., Lee, Y.-M., & Goodson, H. V. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.02.006 · Cited by 1,456 · see citing works
Histone acetyltransferase complexes: one size doesn't fit all
Lee, K. K. W., & Workman, J. L. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2145 · Cited by 1,091 · see citing works
Histone Deacetylase 5 Epigenetically Controls Behavioral Adaptations to Chronic Emotional Stimuli
Renthal, W., Maze, I., Krishnan, V., Covington, H. E., Xiao, G., Kumar, A., Russo, S. J., Graham, A., Tsankova, N., Kippin, T. E., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.09.032 · Cited by 599 · see citing works
Self-citationUnraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases
Lahm, A., Paolini, C., Pallaoro, M., Nardi, M. C., Jones, P., Neddermann, P., Sambucini, S., Bottomley, M. J., Lo Surdo, P., Carfı́, A., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706487104 · Cited by 566 · see citing works
Structure and acetyl-lysine recognition of the bromodomain
Mujtaba, S., Zeng, L., & Zhou, M.-M. (2007) · Oncogene · doi:10.1038/sj.onc.1210618 · Cited by 419 · see citing works
Bottomley, M. J., Surdo, P. L., Giovine, P. D., Cirillo, A., Scarpelli, R., Ferrigno, F., JONES, P. G., Neddermann, P., Francesco, R. D., Steinkühler, C., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803514200 · Cited by 319 · see citing works
Schuetz, A., Min, J., Allali‐Hassani, A., Schapira, M., Shuen, M., Loppnau, P., Mazitschek, R., Kwiatkowski, N. P., Lewis, T. A., Maglathin, R. L., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m707362200 · Cited by 261 · see citing works
Self-citationHistone Deacetylase 7 Silencing Alters Endothelial Cell Migration, a Key Step in Angiogenesis
Mottet, D., Bellahcène, A., Pirotte, S., Waltregny, D., Deroanne, C., Lamour, V., Lidereau, R., & Castronovo, V. (2007) · Circulation Research · doi:10.1161/circresaha.107.149377 · Cited by 192 · see citing works
Intracellular Trafficking of Histone Deacetylase 4 Regulates Neuronal Cell Death
Bolger, T. A., & Yao, T. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1826-05.2005 · Cited by 190 · see citing works
The Histone Deacetylase HDAC4 Connects Neural Activity to Muscle Transcriptional Reprogramming
Cohen, T. J., Waddell, D. S., Barrientos, T., Lu, Z., Feng, G., Cox, G. A., Bodine, S. C., & Yao, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706268200 · Cited by 190 · see citing works
Bowers, A., West, N., Taunton, J., Schreiber, S. L., Bradner, J. E., & Williams, R. M. (2008) · Journal of the American Chemical Society · doi:10.1021/ja8033763 · Cited by 165 · see citing works
Self-citationSternson, S. M., Wong, J. C., Grozinger, C. M., & Schreiber, S. L. (2001) · Organic Letters · doi:10.1021/ol016915f · Cited by 139 · see citing works
Parra, M., Kasler, H. G., McKinsey, T. A., Olson, E. N., & Verdin, E. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m413396200 · Cited by 138 · see citing works
Mechanisms and Molecular Probes of Sirtuins
Smith, B. C., Hallows, W. C., & Denu, J. M. (2008) · Chemistry & Biology · doi:10.1016/j.chembiol.2008.09.009 · Cited by 136 · see citing works
Zhou, X., Richon, V. M., Rifkind, R. A., & Marks, P. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.3.1056 · Cited by 120 · see citing works
Synthesis and Conformation−Activity Relationships of the Peptide Isosteres of FK228 and Largazole
Bowers, A. A., Greshock, T. J., West, N. H., Estiu, G. L., Schreiber, S. L., Wiest, O., Williams, R. M., & Bradner, J. E. (2009) · Journal of the American Chemical Society · doi:10.1021/ja807772w · Cited by 104 · see citing works
Self-citationProbing the elusive catalytic activity of vertebrate class IIa histone deacetylases
JONES, P. G., Altamura, S., Francesco, R. D., Gallinari, P., Lahm, A., Neddermann, P., Rowley, M., Serafini, S., & Steinkühler, C. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.02.025 · Cited by 100 · see citing works
Patel, V. P., Mazitschek, R., Coleman, B. I., Nguyen, C., Urgaonkar, S., Cortese, J. F., Barker, R. H., Greenberg, E. F., Tang, W., Bradner, J. E., et al. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm801654y · Cited by 87 · see citing works
Self-citationFluorous‐Based Small‐Molecule Microarrays for the Discovery of Histone Deacetylase Inhibitors
Vegas, A. J., Bradner, J. E., Tang, W., McPherson, O. M., Greenberg, E. F., Koehler, A. N., & Schreiber, S. L. (2007) · Angewandte Chemie International Edition · doi:10.1002/anie.200703198 · Cited by 86 · see citing works
Self-citationZinc Binding in HDAC Inhibitors: A DFT Study
Wang, D., Helquist, P. M., & Wiest, O. (2007) · The Journal of Organic Chemistry · doi:10.1021/jo070739s · Cited by 72 · see citing works
Riester, D., Wegener, D., Hildmann, C., & Schwienhorst, A. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.09.155 · Cited by 68 · see citing works
The Impact of Multiple Protein Sequence Alignment on Phylogenetic Estimation
Wang, L., Leebens‐Mack, J., Wall, P. K., Beckmann, K., dePamphilis, C. W., & Warnow, T. J. (2009) · IEEE Transactions on Computational Biology and Bioinformatics · doi:10.1109/tcbb.2009.68 · Cited by 66 · see citing works
Self-citationModular Synthesis and Preliminary Biological Evaluation of Stereochemically Diverse 1,3-Dioxanes
Wong, J. C., Sternson, S. M., Louca, J. B., Hong, R., & Schreiber, S. L. (2004) · Chemistry & Biology · doi:10.1016/j.chembiol.2004.07.012 · Cited by 35 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles
Subramanian, A., Narayan, R., Corsello, S. M., Peck, D. D., Natoli, T. E., Lu, X., Gould, J., Davis, J. F., Tubelli, A. A., Asiedu, J. K., et al. (2017) · Cell · doi:10.1016/j.cell.2017.10.049 · Cited by 3,515 · see citing works
Self-citationNew and emerging HDAC inhibitors for cancer treatment
West, A. C., & Johnstone, R. W. (2014) · Journal of Clinical Investigation · doi:10.1172/jci69738 · Cited by 1,404 · see citing works
Epigenetic protein families: a new frontier for drug discovery
Arrowsmith, C. H., Bountra, C., Fish, P. V., Lee, K., & Schapira, M. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3674 · Cited by 1,327 · see citing works
HDACs and HDAC Inhibitors in Cancer Development and TherapyPreprint
Li, Y., & Seto, E. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026831 · Cited by 1,309 · see citing works
Targeting the cancer epigenome for therapy
Jones, P. A., Issa, J. J., & Baylin, S. B. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.93 · Cited by 1,132 · see citing works
Lysine glutarylation is a protein posttranslational modification regulated by SIRT5
Tan, M., Peng, C., Anderson, K. A., Chhoy, P., Xie, Z., Dai, L., Park, J., Chen, Y., Huang, H., Zhang, Y., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.014 · Cited by 844 · see citing works
Class I histone deacetylases (HDAC1–3) are histone lysine delactylases
Moreno-Yruela, C., Zhang, D., Wei, W., Bæk, M., Liu, W., Gao, J., Danková, D., Nielsen, A. L., Bolding, J. E., Yang, L., et al. (2022) · Science Advances · doi:10.1126/sciadv.abi6696 · Cited by 841 · see citing works
Thirty Years of HDAC Inhibitors: 2020 Insight and Hindsight
Ho, T. C. S., Chan, A. H. Y., & Ganesan, A. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00830 · Cited by 795 · see citing works
Tham, Y. K., Bernardo, B. C., Ooi, J. Y. Y., Weeks, K. L., & McMullen, J. R. (2015) · Archives of Toxicology · doi:10.1007/s00204-015-1477-x · Cited by 707 · see citing works
Functionally defined therapeutic targets in diffuse intrinsic pontine glioma
Grasso, C. S., Tang, Y., Truffaux, N., Berlow, N. E., Liu, L., Debily, M.-A., Quist, M. J., Davis, L. E., Huang, E. C., Woo, P. J., et al. (2015) · Nature Medicine · doi:10.1038/nm.3855 · Cited by 687 · see citing works
Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes
Bantscheff, M., Hopf, C., Savitski, M. M., Dittmann, A., Grandi, P., Michon, A.-M., Schlegl, J., Abraham, Y., Becher, I., Bergamini, G., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1759 · Cited by 659 · see citing works
Santo, L., Hideshima, T., Kung, A. L., Tseng, J.-C., Tamang, D., Yang, M., Jarpe, M., van Duzer, J. H., Mazitschek, R., Ogier, W. C., et al. (2012) · Blood · doi:10.1182/blood-2011-10-387365 · Cited by 616 · see citing works
Self-citationHistone deacetylases as regulators of inflammation and immunity
Shakespear, M. R., Halili, M. A., Irvine, K. M., Fairlie, D. P., & Sweet, M. J. (2011) · Trends in Immunology · doi:10.1016/j.it.2011.04.001 · Cited by 546 · see citing works
Epigenetic Therapy Ties MYC Depletion to Reversing Immune Evasion and Treating Lung Cancer
Topper, M. J., Vaz, M., Chiappinelli, K. B., DeStefano Shields, C. E., Niknafs, N., Yen, R.-W. C., Wenzel, A., Hicks, J., Ballew, M., Stone, M., et al. (2017) · Cell · doi:10.1016/j.cell.2017.10.022 · Cited by 537 · see citing works
Delcuve, G. P., Khan, D. H., & Davie, J. R. (2012) · Clinical Epigenetics · doi:10.1186/1868-7083-4-5 · Cited by 505 · see citing works
Epigenetic Therapies for Cancer
Bates, S. E. (2020) · New England Journal of Medicine · doi:10.1056/nejmra1805035 · Cited by 493 · see citing works
Recent developments of HDAC inhibitors: Emerging indications and novel molecules
Bondarev, A. D., Attwood, M. M., Jonsson, J., Chubarev, V. N., Tarasov, V. V., & Schiöth, H. B. (2021) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.14889 · Cited by 440 · see citing works
Lauffer, B. E. L., Mintzer, R., Fong, R., Mukund, S., Tam, C., Zilberleyb, I., Flicke, B., Ritscher, A., Fedorowicz, G., Vallero, R., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.490706 · Cited by 429 · see citing works
“SAHA and TSA exhibited potencies against HDAC1 and HDAC2 comparable with C1 and C2, but their selectivity profiles extended well beyond these isoforms as reported previously (12, 13, 26, 29, 30, 38).”
BackgroundTargeted Cancer Therapy: Giving Histone Deacetylase Inhibitors All They Need To Succeed
Gryder, B. E., Sodji, Q. H., & Oyelere, A. K. (2012) · Future Medicinal Chemistry · doi:10.4155/fmc.12.3 · Cited by 404 · see citing works
Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy
Wagner, J. M., Hackanson, B. W., Lübbert, M., & Jung, M. (2010) · Clinical Epigenetics · doi:10.1007/s13148-010-0012-4 · Cited by 391 · see citing works
Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group
Lobera, M., Madauss, K. P., Pohlhaus, D. T., Wright, Q. G., Trocha, M., Schmidt, D. R., Baloglu, E., Trump, R. P., Head, M. S., Hofmann, G. A., et al. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1223 · Cited by 384 · see citing works
Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair
Lee, J.-H., Choy, M. L., Ngo, L., Foster, S. S., & Marks, P. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008522107 · Cited by 364 · see citing works
Advances and Challenges of HDAC Inhibitors in Cancer Therapeutics
McClure, J. J., Li, X., & Chou, C. J. (2018) · Advances in cancer research · doi:10.1016/bs.acr.2018.02.006 · Cited by 356 · see citing works
On the Promise of Photopharmacology Using Photoswitches: A Medicinal Chemist’s Perspective
Fuchter, M. J. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00629 · Cited by 353 · see citing works
The bromodomain protein Brd4 insulates chromatin from DNA damage signalling
Floyd, S., Pacold, M. E., Huang, Q., Clarke, S. M., Lam, F. C., Cannell, I. G., Bryson, B. D., Rameseder, J., Lee, M. J., Blake, E. J., et al. (2013) · Nature · doi:10.1038/nature12147 · Cited by 330 · see citing works
Self-citationCook, C. N., Carlomagno, Y., Gendron, T. F., Dunmore, J. H., Scheffel, K., Stetler, C. T., Davis, M., Dickson, D. W., Jarpe, M. B., Deture, M. A., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt402 · Cited by 309 · see citing works
Romidepsin: a new therapy for cutaneous T-cell lymphoma and a potential therapy for solid tumors
Grant, C. M., Rahman, F., Piekarz, R., Peer, C. J., Frye, R., Robey, R. W., Gardner, E. R., Figg, W. D., & Bates, S. E. (2010) · Expert Review of Anticancer Therapy · doi:10.1586/era.10.88 · Cited by 294 · see citing works
Target engagement and drug residence time can be observed in living cells with BRET
Robers, M. B., Dart, M. L., Woodroofe, C. C., Zimprich, C., Kirkland, T. A., Machleidt, T., Kupcho, K. R., Levin, S., Hartnett, J. R., Zimmerman, K., et al. (2015) · Nature Communications · doi:10.1038/ncomms10091 · Cited by 275 · see citing works
Acetylation site specificities of lysine deacetylase inhibitors in human cells
Schölz, C., Weinert, B. T., Wagner, S., Beli, P., Miyake, Y., Qi, J., Jensen, L. J., Streicher, W. W., McCarthy, A. R., Westwood, N. J., et al. (2015) · Nature Biotechnology · doi:10.1038/nbt.3130 · Cited by 271 · see citing works
Self-citationTargeting Metalloenzymes for Therapeutic Intervention
Chen, A. Y., Adamek, R. N., Dick, B. L., Credille, C. V., Morrison, C. N., & Cohen, S. M. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00201 · Cited by 277 · see citing works
Chronic Pain: Emerging Evidence for the Involvement of Epigenetics
Denk, F., & McMahon, S. B. (2012) · Neuron · doi:10.1016/j.neuron.2012.01.012 · Cited by 267 · see citing works
Rational Therapeutic Combinations with Histone Deacetylase Inhibitors for the Treatment of Cancer
Thurn, K. T., Thomas, S., Moore, A. P., & Münster, P. N. (2011) · Future Oncology · doi:10.2217/fon.11.2 · Cited by 249 · see citing works
Determining target engagement in living systems
Simon, G. M., Niphakis, M. J., & Cravatt, B. F. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1211 · Cited by 246 · see citing works
Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors
Kalin, J. H., Wu, M., Gómez, A. V., Song, Y., Das, J., Hayward, D., Adejola, N., Wu, M., Panova, I. P., Chung, H. J., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02242-4 · Cited by 239 · see citing works
Self-citationTherapeutic potential for HDAC inhibitors in the heart
McKinsey, T. A. (2012) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134712 · Cited by 230 · see citing works
HDAC Inhibitors in Acute Myeloid Leukemia
José‐Eneriz, E. S., Gimenez-Camino, N., Agirre, X., & Prósper, F. (2019) · Cancers · doi:10.3390/cancers11111794 · Cited by 228 · see citing works
Coiffier, B., Pro, B., Prince, H. M., Foss, F. M., Sokol, L., Greenwood, M. J., Caballero, D. M., Morschhauser, F., Wilhelm, M., Pinter‐Brown, L. C., et al. (2014) · Journal of Hematology & Oncology · doi:10.1186/1756-8722-7-11 · Cited by 212 · see citing works
Bradner, J. E., Mak, R., Tanguturi, S. K., Mazitschek, R., Haggarty, S. J., Ross, K., Chang, C. Y., Bosco, J., West, N., Morse, E., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006774107 · Cited by 211 · see citing works
Self-citationMarcaurelle, L. A., Comer, E., Dandapani, S., Duvall, J. R., Gerard, B., Kesavan, S., Lee, M. D., Liu, H., Lowe, J. T., Marié, J., et al. (2010) · Journal of the American Chemical Society · doi:10.1021/ja105119r · Cited by 211 · see citing works
Self-citationNamdar, M., Perez, G., Ngo, L., & Marks, P. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013754107 · Cited by 207 · see citing works
Histone deacetylase 10 structure and molecular function as a polyamine deacetylase
Hai, Y., Shinsky, S. A., Porter, N. J., & Christianson, D. W. (2017) · Nature Communications · doi:10.1038/ncomms15368 · Cited by 200 · see citing works
Multiple roles of class I HDACs in proliferation, differentiation, and development
Reichert, N., Choukrallah, M.-A., & Matthias, P. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-0921-9 · Cited by 194 · see citing works
Development of the first small molecule histone deacetylase 6 (HDAC6) degraders
Yang, K., Song, Y., Xie, H., Wu, H., Wu, Y.-T., Leisten, E. D., & Tang, W. (2018) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2018.05.057 · Cited by 190 · see citing works
Pipalia, N. H., Cosner, C. C., Huang, A. Y., Chatterjee, A., Bourbon, P., Farley, N., Helquist, P. M., Wiest, O., & Maxfield, F. R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1014890108 · Cited by 186 · see citing works
Rettig, I., Koeneke, E., Trippel, F., Mueller, W. C., Burhenne, J., Kopp‐Schneider, A., Fabian, J., Schober, A., Fernekorn, U., von Deimling, A., et al. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.24 · Cited by 184 · see citing works
How Chemoproteomics Can Enable Drug Discovery and Development
Moellering, R. E., & Cravatt, B. F. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.01.001 · Cited by 182 · see citing works
Marek, M., Kannan, S., Hauser, A.-T., Moraes Mourão, M., Caby, S., Cura, V., Stolfa, D. A., Schmidtkunz, K., Lancelot, J., Andrade, L., et al. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003645 · Cited by 173 · see citing works
Cavasin, M. A., Demos‐Davies, K., Horn, T. R., Walker, L. A., Lemon, D. D., Birdsey, N., Weiser‐Evans, M. C. M., Harral, J. W., Irwin, D. C., Anwar, A., et al. (2012) · Circulation Research · doi:10.1161/circresaha.111.258426 · Cited by 175 · see citing works
Therapeutic targets for cardiac fibrosis: from old school to next-gen
Travers, J. G., Tharp, C. A., Rubino, M., & McKinsey, T. A. (2022) · Journal of Clinical Investigation · doi:10.1172/jci148554 · Cited by 176 · see citing works
HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain
Denk, F., Huang, W. L., Sidders, B. S., Bithell, A., Crow, M., Grist, J., Sharma, S., Ziemek, D., Rice, A. S. C., Buckley, N. J., et al. (2013) · Pain · doi:10.1016/j.pain.2013.05.021 · Cited by 172 · see citing works
Jia, H., Pallos, J., Jacques, V., Lau, A., Tang, B., Cooper, A. C., Syed, A., Purcell, J. M., Chen, Y., Sharma, S., et al. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.01.016 · Cited by 170 · see citing works
Jochems, J., Boulden, J., Lee, B. G., Blendy, J. A., Jarpe, M. B., Mazitschek, R., van Duzer, J. H., Jones, S. S., & Berton, O. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.207 · Cited by 168 · see citing works
Self-citationRomidepsin: a novel histone deacetylase inhibitor for cancer
Bertino, E. M., & Otterson, G. A. (2011) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2011.594437 · Cited by 169 · see citing works
HDAC inhibitors and immunotherapy; a double edged sword?
Kroesen, M., Gielen, P. R., Brok, I. C., Armandari, I., Hoogerbrugge, P. M., & Adema, G. J. (2014) · Oncotarget · doi:10.18632/oncotarget.2289 · Cited by 167 · see citing works
CAR-T cell combination therapy: the next revolution in cancer treatment
Al-Haideri, M. T., Tondok, S. B., Safa, S. H., Maleki, A. H., Rostami, S. M., Jalil, A. T., Al-Gazally, M. E., Alsaikhan, F., Rizaev, J. A., Mohammad, T. A. M., et al. (2022) · Cancer Cell International · doi:10.1186/s12935-022-02778-6 · Cited by 167 · see citing works
Foxp3 Post-translational Modifications and Treg Suppressive Activity
Deng, G., Song, X., Fujimoto, S., Piccirillo, C. A., Nagai, Y., & Greene, M. I. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02486 · Cited by 166 · see citing works
Histone deacetylase 3 as a novel therapeutic target in multiple myeloma
Minami, J., Suzuki, R., Mazitschek, R., Gorgun, G., Ghosh, B., Cirstea, D., Hu, Y., Mimura, N., Ohguchi, H., Cottini, F., et al. (2014) · Leukemia · doi:10.1038/leu.2013.231 · Cited by 159 · see citing works
Self-citationGhosh, S. K., Perrine, S. P., Williams, R. M., & Faller, D. V. (2011) · Blood · doi:10.1182/blood-2011-06-362434 · Cited by 159 · see citing works
Ha, K., Fiskus, W. C., Choi, D. S., Bhaskara, S., Cerchietti, L. C. A., Devaraj, S. G. T., Shah, B., Sharma, S., Chang, J. C., Melnick, A. M., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.2154 · Cited by 157 · see citing works
Bürli, R. W., Luckhurst, C. A., Aziz, O., Matthews, K. L., Yates, D., Lyons, K. A., Beconi, M., McAllister, G., Breccia, P., Stott, A. J., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm4011884 · Cited by 153 · see citing works
Luo, X., Liu, Y., Kubicek, S., Myllyharju, J., Tumber, A., Ng, S. S., Che, K. H., Podoll, J. D., Heightman, T. D., Oppermann, U. C. T., et al. (2011) · Journal of the American Chemical Society · doi:10.1021/ja201597b · Cited by 153 · see citing works
Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-κB-mediated inflammation
Leus, N. G. J., Zwinderman, M. R. H., & Dekker, F. J. (2016) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2016.06.019 · Cited by 152 · see citing works
Histone deacetylase inhibitors in hematological malignancies and solid tumors
Chun, P. (2015) · Archives of Pharmacal Research · doi:10.1007/s12272-015-0571-1 · Cited by 147 · see citing works
Roles of Histone Deacetylases and Inhibitors in Anticancer Therapy
Verza, F. A., Das, U., Fachin, A. L., Dimmock, J. R., & Marins, M. (2020) · Cancers · doi:10.3390/cancers12061664 · Cited by 147 · see citing works
Espallergues, J., Teegarden, S. L., Veerakumar, A., Boulden, J., Challis, C., Jochems, J., Chan, M., Petersen, T. L., Deneris, E. S., Matthias, P., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5634-11.2012 · Cited by 147 · see citing works
Hideshima, T., Qi, J., Paranal, R. M., Tang, W., Greenberg, E. F., West, N. H., Colling, M. E., Estiu, G. L., Mazitschek, R., Perry, J. A., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1608067113 · Cited by 146 · see citing works
Self-citationChemical genomics reveals histone deacetylases are required for core regulatory transcription
Gryder, B. E., Wu, L., Woldemichael, G. M., Pomella, S., Quinn, T. R., Park, P. M. C., Cleveland, A. H., Stanton, B. Z., Song, Y., Rota, R., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11046-7 · Cited by 143 · see citing works
Histone deacetylase 11 is an ε-N-Myristoyllysine hydrolase
Moreno-Yruela, C., Galleano, I., Madsen, A. S., & Olsen, C. A. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2018.04.007 · Cited by 149 · see citing works
Molecular basis of organ fibrosis: Potential therapeutic approaches
Ghosh, A. K., Quaggin, S. E., & Vaughan, D. E. (2013) · Experimental Biology and Medicine · doi:10.1177/1535370213489441 · Cited by 140 · see citing works
Development of a histone deacetylase 6 inhibitor and its biological effects
Lee, J.-H., Mahendran, A., Yao, Y., Ngo, L., Venta-Perez, G., Choy, M. L., Kim, N., Ham, W.-S., Breslow, R., & Marks, P. A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1313893110 · Cited by 141 · see citing works
Selective HDAC inhibition by ACY-241 enhances the activity of paclitaxel in solid tumor models
Huang, P., Almeciga-Pinto, I., Jarpe, M. B., van Duzer, J. H., Mazitschek, R., Yang, M., Jones, S. S., & Quayle, S. N. (2016) · Oncotarget · doi:10.18632/oncotarget.13738 · Cited by 135 · see citing works
Self-citationA Proton-Shuttle Reaction Mechanism for Histone Deacetylase 8 and the Catalytic Role of Metal Ions
Wu, R., Wang, S., Zhou, N., Cao, Z., & Zhang, Y. (2010) · Journal of the American Chemical Society · doi:10.1021/ja103932d · Cited by 135 · see citing works
Romidepsin for the Treatment of Peripheral T-Cell Lymphoma
Iyer, S. P., & Foss, F. M. (2015) · The Oncologist · doi:10.1634/theoncologist.2015-0043 · Cited by 134 · see citing works
Horton, J. R., Engstrom, A., Zoeller, E. L., Liu, X., Shanks, J. R., Zhang, X., Johns, M. A., Vertino, P. M., Fu, H., & Cheng, X. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.698449 · Cited by 131 · see citing works
Development and Therapeutic Implications of Selective Histone Deacetylase 6 Inhibitors
Kalin, J. H., & Bergman, J. A. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm4001659 · Cited by 129 · see citing works
Madsen, A. S., & Olsen, C. A. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201203754 · Cited by 122 · see citing works
Wang, Y., Stowe, R. L., Pinello, C. E., Tian, G., Madoux, F., Li, D., Zhao, L. Y., Li, J.-L., Wang, Y., Wang, Y., et al. (2015) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.12.015 · Cited by 122 · see citing works
Chromatin as an expansive canvas for chemical biology
Fierz, B., & Muir, T. W. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.938 · Cited by 121 · see citing works
Hanson, J. E., La, H., Plise, E., Chen, Y.-H., Ding, X., Hanania, T., Sabath, E. V., Alexandrov, V., Brunner, D., Leahy, E., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069964 · Cited by 121 · see citing works
Cherng, C., Lee, K.-C., Chien, C., Chou, K.-Y., Cheng, Y., Hsin, S.-T., Lee, S.-O., Shen, C., Tsai, R., & Wong, C. (2013) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2013.04.007 · Cited by 119 · see citing works
Chemical Genetics–Based Target Identification in Drug Discovery
Cong, F., Cheung, A. K., & Huang, S.-M. A. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134639 · Cited by 118 · see citing works
Strategies To Design Selective Histone Deacetylase Inhibitors
Melesina, J., Simoben, C. V., Praetorius, L., Bülbül, E. F., Robaa, D., & Sippl, W. (2021) · ChemMedChem · doi:10.1002/cmdc.202000934 · Cited by 118 · see citing works
LAceP: Lysine Acetylation Site Prediction Using Logistic Regression Classifiers
Hou, T., Zheng, G., Zhang, P., Jia, J., Li, J., Xie, L., Wei, C., & Li, Y. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089575 · Cited by 118 · see citing works
Konstantinopoulos, P. A., Wilson, A. J., Saskowski, J. L., Wass, E., & Khabele, D. (2014) · Gynecologic Oncology · doi:10.1016/j.ygyno.2014.03.007 · Cited by 114 · see citing works
Cardiac HDAC6 catalytic activity is induced in response to chronic hypertension
Lemon, D. D., Horn, T. R., Cavasin, M. A., Jeong, M. Y., Haubold, K. W., Long, C. S., Irwin, D. C., McCune, S. A., Chung, E., Leinwand, L. A., et al. (2011) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2011.04.005 · Cited by 114 · see citing works
Target deconvolution of HDAC pharmacopoeia reveals MBLAC2 as common off-target
Lechner, S., Malgapo, M. I. P., Grätz, C., Steimbach, R. R., Baron, A., Rüther, P. L., Nadal, S., Stumpf, C., Loos, C., Ku, X., et al. (2022) · Nature Chemical Biology · doi:10.1038/s41589-022-01015-5 · Cited by 114 · see citing works
Selective HDAC1/HDAC2 Inhibitors Induce Neuroblastoma Differentiation
Frumm, S. M., Fan, Z. P., Ross, K. N., Duvall, J. R., Gupta, S., VerPlank, L., Suh, B., Holson, E. B., Wagner, F. F., Smith, W. B., et al. (2013) · Chemistry & Biology · doi:10.1016/j.chembiol.2013.03.020 · Cited by 113 · see citing works
Self-citationHDAC8 catalyzes the hydrolysis of long chain fatty acyl lysine
Aramsangtienchai, P., Spiegelman, N. A., He, B., Miller, S. P., Dai, L., Zhao, Y., & Lin, H. (2016) · ACS Chemical Biology · doi:10.1021/acschembio.6b00396 · Cited by 118 · see citing works
Investigating the Sensitivity of NAD+-dependent Sirtuin Deacylation Activities to NADH
Madsen, A. S., Andersen, C. D., Daoud, M., Anderson, K. A., Laursen, J. S., Chakladar, S., Huynh, F. K., Colaço, A. R., Backos, D. S., Fristrup, P., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.668699 · Cited by 110 · see citing works
Epigenetic mechanisms of neuroplasticity and the implications for stroke recovery
Felling, R. J., & Song, H. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.09.017 · Cited by 111 · see citing works
Wu, R., Lu, Z., Cao, Z., & Zhang, Y. (2011) · Journal of the American Chemical Society · doi:10.1021/ja111104p · Cited by 108 · see citing works
Koppel, I., & Timmusk, T. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.07.015 · Cited by 108 · see citing works
Mechanisms of Resistance to Histone Deacetylase Inhibitors
Lee, J., Choy, M. L., & Marks, P. A. (2012) · Advances in cancer research · doi:10.1016/b978-0-12-394387-3.00002-1 · Cited by 108 · see citing works
Fass, D. M., Reis, S. A., Ghosh, B., Hennig, K. M., Joseph, N. F., Zhao, W., Nieland, T. J. F., Guan, J., Kuhnle, C. G., Tang, W., et al. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.06.043 · Cited by 106 · see citing works
Self-citationYap, T. A., & Workman, P. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134532 · Cited by 104 · see citing works
HDAC1 and HDAC2 integrate the expression of p53 mutants in pancreatic cancer
Stojanovic, N., Hassan, Z., Wirth, M., Wenzel, P., Beyer, M., Schäfer, C., Brand, P., Kroemer, A., Stauber, R. H., Schmid, R. M., et al. (2016) · Oncogene · doi:10.1038/onc.2016.344 · Cited by 106 · see citing works
Kerr, E. M., Holohan, C., McLaughlin, K. M., Majkut, J., Dolan, S., Redmond, K. M., Riley, J. S., McLaughlin, K. M., Stasik, I., Crudden, M. T. C. M., et al. (2012) · Cell Death and Differentiation · doi:10.1038/cdd.2012.8 · Cited by 106 · see citing works
Epigenetic Changes in Pediatric Solid Tumors: Promising New Targets
Lawlor, E. R., & Thiele, C. J. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1921 · Cited by 104 · see citing works
A Novel Class of Small Molecule Inhibitors of HDAC6
Inks, E. S., Josey, B. J., Jesinkey, S. R., & Chou, C. J. (2011) · ACS Chemical Biology · doi:10.1021/cb200134p · Cited by 103 · see citing works
HDAC-dependent ventricular remodeling
Xie, M., & Hill, J. A. (2013) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2012.12.006 · Cited by 103 · see citing works
- Authors
- Bradner, J. E., West, N., Grachan, M. L., Greenberg, E. F., Haggarty, S. J., Warnow, T., & Mazitschek, R.
- Affiliations
- Broad Institute (US)
- Harvard University (US)
- The University of Texas at Austin (US)
- Corresponding author
- Bradner, James E
- Mazitschek, Ralph
- Venue
- Nature Chemical Biology
- Published
- 2010-02-07
- Volume
- 6
- Issue
- 3
- Pages
- 238-243
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC2822059
- OpenAlex
- W2083784041
- Semantic Scholar
- 68c4985bcae290a761e64065e7e4cfe062700c7f
- Cited by
- 720
- References
- 31
- Citations by year
- 2026: 18 · 2025: 25 · 2024: 27 · 2023: 28 · 2022: 37 · 2021: 50 · 2020: 41 · 2019: 34 · 2018: 39 · 2017: 42 · 2016: 61 · 2015: 64 · 2014: 53 · 2013: 67 · 2012: 62
- FWCI
- 27.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust
- National Institutes of Health (n01co12400-79-0-22)
- Centers for Disease Control and Prevention (N01-C0-012400)
- National Institute on Drug Abuse (R01DA028301)
- National Cancer Institute (N01-CO-012400, K08CA128972, P01CA078048, T32CA079443)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- histone deacetylase, histone deacetylase inhibitors, isoform selectivity, class I HDACs, class II HDACs, class IIa HDACs, focused libraries, chemical probes, enzyme inhibition mechanism
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
