The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes
Abstract
The development of selective histone deacetylase (HDAC) inhibitors with anti-cancer and anti-inflammatory properties remains challenging in large part owing to the difficulty of probing the interaction of small molecules with megadalton protein complexes. A combination of affinity capture and quantitative mass spectrometry revealed the selectivity with which 16 HDAC inhibitors target multiple HDAC complexes scaffolded by ELM-SANT domain subunits, including a novel mitotic deacetylase complex (MiDAC). Inhibitors clustered according to their target profiles with stronger binding of aminobenzamides to the HDAC NCoR complex than to the HDAC Sin3 complex. We identified several non-HDAC targets for hydroxamate inhibitors. HDAC inhibitors with distinct profiles have correspondingly different effects on downstream targets. We also identified the anti-inflammatory drug bufexamac as a class IIb (HDAC6, HDAC10) HDAC inhibitor. Our approach enables the discovery of novel targets and inhibitors and suggests that the selectivity of HDAC inhibitors should be evaluated in the context of HDAC complexes and not purified catalytic subunits.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Genetic or pharmacological targeting of the CoREST complex enhances anti-tumour activity in mice (Bantscheff et al., 2011;Xiong et al., 2020).”
From HDACs and the epigenetic plasticity of cancer cells: target the complexity (2022) · cites this paper as Bantscheff et al., 2011
Citations
Cites
Chromatin modifications and their function
Kouzarides, T. (2007) · Cell · doi:10.1016/j.cell.2007.02.005 · Cited by 10,883
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
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
Proteome survey reveals modularity of the yeast cell machinery
Gavin, A., Aloy, P., Grandi, P., Krause, R., Böesche, M., Marzioch, M., Rau, C., Jensen, L. J., Bastuck, S., Dümpelfeld, B., et al. (2006) · Nature · doi:10.1038/nature04532 · Cited by 2,570
Self-citationPvclust: an R package for assessing the uncertainty in hierarchical clustering
Suzuki, R., & Shimodaira, H. (2006) · Bioinformatics · doi:10.1093/bioinformatics/btl117 · Cited by 2,456
Regulation of cellular metabolism by protein lysine acetylation
Zhao, S., Xu, W., Jiang, W., Yu, W., Lin, Y., Zhang, T., Yao, J., Zhou, L., Zeng, Y., Li, H., et al. (2010) · Science · doi:10.1126/science.1179689 · Cited by 1,910
A Mammalian Histone Deacetylase Related to the Yeast Transcriptional Regulator Rpd3p
Taunton, J., Hassig, C. A., & Schreiber, S. L. (1996) · Science · doi:10.1126/science.272.5260.408 · Cited by 1,829
Olsen, J. V., de Godoy, L. M. F., Li, G., Maček, B., Mortensen, P., Pesch, R., Makarov, A., Lange, O., Horning, S. R., & Mann, M. (2005) · Molecular & Cellular Proteomics · doi:10.1074/mcp.t500030-mcp200 · Cited by 1,539
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
The Cell as a Collection of Protein Machines: Preparing the Next Generation of Molecular Biologists
Alberts, B. (1998) · Cell · doi:10.1016/s0092-8674(00)80922-8 · Cited by 1,411
Flagged first, then by citations
Cited by
Sorted by citations
Items 601–683 of 683
Development and Evaluation of Chemical Probes for the Study of Histone Demethylases
Marholz, L. J. (2015) · CU Scholar (University of Colorado Boulder)
Role of endogenous retrovirus promoter activity in tumor suppression
Krönung, S. K. (2015) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-5097
Stress management : multilayer regulation of the heat shock response
Budzyński, M. A. (2017) · Doria (University of Helsinki) · doi:10.13140/rg.2.2.16736.48641
HDACi-induced DNA damage: identifying potential endpoints for safety assessment
Wang, W. (2016) · ORCA Online Research @Cardiff (Cardiff University)
Targeting lysine acetylation in inflammatory lung diseases
van den Bosch, T. (2017) · University of Groningen research database (University of Groningen / Centre for Information Technology)
Wright, L. C. (2017) · Figshare
Combinations of Genomically and Immune-Targeted Therapies in Early-Phase Clinical Trials
Patel, M. R., Patel, S. P., & Kurzrock, R. (2017) · Current cancer research · doi:10.1007/978-3-319-63757-0_9
The Epigenetics of Autoimmunity and Epigenetic Drug Discovery
Tough, D. F., Rioja, I., Tak, P. P., & Prinjha, R. K. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-809912-4.00015-5
Mass Spectrometry and Chemical Biology in Epigenetics Drug Discovery
Feller, C., Weigt, D., & Hopf, C. (2019) · Methods and principles in medicinal chemistry · doi:10.1002/9783527809257.ch4
Self-citationAziee, S., Yassim, H. M., Yusoff, S. M., Shamsuddin, S., Wahab, R. A., & Johan, M. F. (2019) · Asia-Pacific Journal of Molecular Biology and Biotechnology · doi:10.35118/apjmbb.2019.027.3.02
Evolutionary, structural and functional features of cellular signalling networks
Lang, B. (2012) · Apollo (University of Cambridge) · doi:10.17863/cam.39120
Proteomics-based drug discovery and chemoproteomics
Colzani, M., & Carini, M. (2014) · doi:10.4155/ebo.13.350
Hydroxamic Acid-Containing Peptides in the Study of Histone Deacetylases
Moreno–Yruela, C., & Olsen, C. A. (2019) · Topics in medicinal chemistry · doi:10.1007/7355_2019_69
Histone deacetylase inhibitors butyrate and bufexamac inhibit de novo HIV-1 infection in CD4 T-cellsPreprint
Chen, L., Zutz, A., Philippou‐Massier, J., Liebner, T., Keppler, O. T., Choudhary, C., Blum, H., & Schölz, C. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.29.067884
A New Drug Discovery Approach Based on Thermal Proteome Profiling to Develop More Effective Drugs
Gholizadeh, E., Rezaei–Tavirani, M., Emadi, A., Karbalaei, R., & Khaleghian, A. (2021) · Middle East Journal of Rehabilitation and Health Studies · doi:10.5812/mejrh.113533
Recent Advances in Small Molecule Target Identification Methods
Beckwith, R. E. J., & Jain, R. K. (2013) · Annual reports in medicinal chemistry · doi:10.1016/b978-0-12-417150-3.00019-3
Wang, X., Rosikiewicz, W., Sedkov, Y., Mondal, B., Kallappagoudar, S., Tvardovskiy, A., Bajpai, R., Xu, B., Pruett‐Miller, S. M., Schneider, R., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.12.17.473155
Genetic and functional analysis of rat mammary cancer susceptibility.
Duderstadt, E. L. (2021) · ThinkIR: The University of Louisville's Institutional Repository (University of Louisville) · doi:10.18297/etd/3628
Epigenetic Contributions to Human Cancer
Baylin, S. B. (2022) · Wiley eBooks · doi:10.1002/9781119000822.hfcm006.pub2
Inhibition of lysine-specific demethylase 1 enzyme activity by TAK-418 as a novel therapy for autism
Matsuda, S., & Kimura, H. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-824421-0.00017-5
Lee, H.-S., Lee, N., Kouprina, N., Kim, J.-H., Kagansky, A., Bates, S. E., Trepel, J. B., Pommier, Y. G., Sackett, D. L., & Larionov, V. (2023) · doi:10.1158/0008-5472.22408425
Lei, X., Ou, Z., Yang, Z., Zhong, J., Zhu, Y., Jing, T., Wu, J., Deng, H., Lin, X., Peng, Y., et al. (2023) · doi:10.1158/1078-0432.c.6530657
Lee, H.-S., Lee, N., Kouprina, N., Kim, J.-H., Kagansky, A., Bates, S. E., Trepel, J. B., Pommier, Y. G., Sackett, D. L., & Larionov, V. (2023) · doi:10.1158/0008-5472.22408425.v1
Epigenetic regulation: Histone modifying enzymes as targets for novel therapeutics
Dietrich, N., & Archer, T. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-824010-6.00067-8
Wilhelm, E., Poirier, M., Bédard, M., McDonald, P. P., Lavigne, P., Hunter, C. L., & Bell, B. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.14.567009
IMAGE-GUIDED SYNTHESIS REVEALS POTENT BLOOD-BRAIN BARRIER PERMEABLE HISTONE DEACETYLASE INHIBITORS
GANTALA, K., & SREENANCHA, G. (2019) · Türk bilgisayar ve matematik eğitimi dergisi · doi:10.61841/turcomat.v10i3.14496
Qiu, H., Su, N., Wang, J., Yan, S., & Li, J. (2023) · Figshare · doi:10.6084/m9.figshare.22619659
Qiu, H., Su, N., Wang, J., Yan, S., & Li, J. (2023) · Figshare · doi:10.6084/m9.figshare.22619656
Qiu, H., Su, N., Wang, J., Yan, S., & Li, J. (2023) · Figshare · doi:10.6084/m9.figshare.22619653
Qiu, H., Su, N., Wang, J., Yan, S., & Li, J. (2023) · Figshare · doi:10.6084/m9.figshare.22619650
Emerging Technologies for Epigenetic Drug Discovery
(2024) · Royal Society of Chemistry eBooks · doi:10.1039/9781837674916-part2
Mass Spectrometry and Chemical Biology Approaches for Deconvoluting Epigenetic Targets
Burton, A. J., Hamza, G. M., Iannetta, A. A., Miele, E., & Zhang, A. X. (2024) · Royal Society of Chemistry eBooks · doi:10.1039/9781837674916-00050
Wu, J., Chaudhuri, S., Feid, S. C., Joshi, H., Pan, M., Kawaji, Q., Liu, G., & Javid, B. (2026) · mBio · doi:10.1128/mbio.02056-26
Chemoproteomics Sheds Light on Epigenetic Targets of [11C]Martinostat in the Human Brain
Catanese, M. C., Klingl, Y. E., Gilbert, T. M., Strebl, M. G., Hartigan, C. R., Schenone, M., & Hooker, J. M. (2025) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.4c00781
Lavallée‐Adam, M., Pelletier, A. R., Diedrich, J. K., Pinto, A. F. M., Martínez‐Bartolomé, S., Petrascheck, M., Moresco, J. J., & Yates, J. R. (2025) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.4c00269
Zhao, T., He, L., Wong, L. P., Mei, S., Xia, J., Xu, Y., Vranken, J. G. V., Mazzola, M. C., Chen, L., Rhee, C., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.25.650293
Knockout of SIN3B modulates transcriptional programs and cell survival in cutaneous melanoma
Matsuyama, L. S. A. S., Harle, V. J., Offord, V., Droop, A., Rabbie, R., Garg, M., Vázquez‐Cruz, M. E., Robles‐Espinoza, C. D., Turner, G., Fraser, D., et al. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107785
Seidel, J., Schönfeld, C., Sindlinger, J., Eirich, J., Kirchgäßner, S., Kreienkamp, N., Schulze‐Osthoff, K., Finkemeier, I., Hailfinger, S., & Schwarzer, D. (2025) · Angewandte Chemie · doi:10.1002/ange.202510967
Rapid degradation of 6 class I HDAC complexes reveals minimal functional overlap between complexesPreprint
Turnbull, R. E., Gonchar, O., English, D. M., Wright, T. A., Baker, I. M., Sirvydis, K., Cowley, S. M., & Schwabe, J. W. R. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.21.671480
Zemskaya, A. S., Kochetkov, S. N., & Kozlov, M. V. (2025) · Molecular Biology · doi:10.1134/s002689332570027x
Mirehei, M., Motamedi, F., Maghsoudi, N., Khodagholi, F., & Abbaszadeh, F. (2025) · Economy of Tajikistan · doi:10.61882/phypha.29.3.260
Fairall, L., Sirvydis, K., Turnbull, R. E., Knottnerus, S. J. G., Gonchar, O., Muskett, F. W., Jukes‐Jones, R., van Brussel, L., van de Geer, E., van Gassen, K. L. I., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-65472-x
DNTTIP1 drives leukaemogenesis through MiDAC‐mediated epigenetic silencing of BMF
Xiu, R., Ma, Y., Gao, Y., Chen, Y., Li, X., Wu, Y., Sun, M., Li, Q., Zhao, Y., Xu, S., et al. (2026) · Clinical and Translational Medicine · doi:10.1002/ctm2.70603
Caractérisation de protéines nucléaires ciblées par la bactérie pathogène Listeria monocytogenes
Pourpre, R. (2019) · theses.fr (ABES) · doi:10.70675/3e0b933ez114cz48e2zae8dzabf6fa8d37b1
Benaissa, M. (2018) · theses.fr (ABES) · doi:10.70675/19229be6zcf7cz4317z80f0ze5bd9b22c989
Ramos‐Morales, E. (2021) · theses.fr (ABES) · doi:10.70675/c6b28473zf6b6z4024z99bfz05629f0484d7
Thomine, C. (2023) · theses.fr (ABES) · doi:10.70675/d1e538f7z6e75z441az8e0fza6253fc7ebf8
Akman, B., Gürsoy, S., Gençpınar, P., Polat, A., Hız, A. S., Oktay, Y., Barakat, T. S., Özbek, U., & Erkek, S. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1777625
ENO1 couples HDAC1 to regulate histone lactylation and gene transcription
Zhai, G., Zhao, F., Wang, Y., Jiang, Z., Li, Y., Fan, Z., Zheng, W., Han, Y., Zhang, J., Zang, Y., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2535245123
Zhang, Y., Zhang, J., & Cao, Y. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1886398
Histone deacetylases in neurodegeneration and neuronal plasticity
Mehta, B., Nambiar, S., Shirke, O., Pandita, S., & Markandeya, Y. S. (2026) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2026.06.025
Investigation of the classical histone deacetylases and sirtuins using peptide technologies
Rogers, J. M., & Olsen, C. A. (2026) · Cell chemical biology · doi:10.1016/j.chembiol.2026.08.009
BindingDB (2016) · UC San Diego · doi:10.7270/q2hh6mtx
BindingDB (2016) · UC San Diego · doi:10.7270/q29c700v
BindingDB (2016) · UC San Diego · doi:10.7270/q2fn17z1
BindingDB (2023) · UC San Diego · doi:10.7270/q2xg9w57
BindingDB (2021) · UC San Diego · doi:10.7270/q2x63rdp
BindingDB (2014) · UC San Diego · doi:10.7270/q29g5p7j
BindingDB (2019) · UC San Diego · doi:10.7270/q2g44sqs
BindingDB Entry 7446: New IDH1 mutant inhibitors for treatment of acute myeloid leukemia
BindingDB (2016) · UC San Diego · doi:10.7270/q2rr1x2g
Class I Lysine Deacetylases Facilitate Glucocorticoid Receptor-Mediated Transcriptional Activation
Kadiyala, V. (2013) · UA Campus Repository (The University of Arizona)
Metadata
- Authors
- Bantscheff, M., Hopf, C., Savitski, M. M., Dittmann, A., Grandi, P., Michon, A.-M., Schlegl, J., Abraham, Y., Becher, I., Bergamini, G., Boesche, M., Delling, M., Dümpelfeld, B., Eberhard, D., Huthmacher, C., Mathieson, T., Poeckel, D., Reader, V., Strunk, K., Sweetman, G., Kruse, U., Neubauer, G., Ramsden, N. G., & Drewes, G.
- Corresponding author
- Bantscheff, Marcus
- Drewes, Gerard
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2011-01-23
- Volume
- 29
- Issue
- 3
- Pages
- 255-265
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2007139310
- Cited by
- 659
- References
- 50
- Citations by year
- 2026: 15 · 2025: 32 · 2024: 25 · 2023: 33 · 2022: 40 · 2021: 37 · 2020: 33 · 2019: 37 · 2018: 33 · 2017: 46 · 2016: 69 · 2015: 68 · 2014: 54 · 2013: 58 · 2012: 49
- FWCI
- 24.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Keywords
- histone deacetylase inhibitors, chemoproteomics, hydroxamate inhibitors, bufexamac, HDAC6, HDAC10, drug selectivity, affinity capture
- MeSH terms
- Histone Deacetylases, Peptide Mapping, Mass Spectrometry, Protein Interaction Mapping, Proteomics
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