Development of a histone deacetylase 6 inhibitor and its biological effects

HDAC6 is a microtubule-associated deacetylase

Hubbert, C., Guardiola, A., Shao, R., Kawaguchi, Y., Ito, A., Nixon, A., Yoshida, M., Wang, X.-F., & Yao, T.-P. (2002) · Nature · doi:10.1038/417455a · Cited by 2,403

The Deacetylase HDAC6 Regulates Aggresome Formation and Cell Viability in Response to Misfolded Protein Stress

Kawaguchi, Y., Kovacs, J. J., McLaurin, A. C., Vance, J. M., Ito, A., & Yao, T. (2003) · Cell · doi:10.1016/s0092-8674(03)00939-5 · Cited by 1,529

Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug

Marks, P. A., & Breslow, R. (2007) · Nature Biotechnology · doi:10.1038/nbt1272 · Cited by 1,198

HDAC6 Regulates Hsp90 Acetylation and Chaperone-Dependent Activation of Glucocorticoid Receptor

Kovacs, J. J., Murphy, P. J. M., Gaillard, S., Zhao, X., Wu, J.-T., Nicchitta, C. V., Yoshida, M., Toft, D. O., Pratt, W. B., & Yao, T.-P. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.04.021 · Cited by 1,153

Trehalose, a Novel mTOR-independent Autophagy Enhancer, Accelerates the Clearance of Mutant Huntingtin and α-Synuclein

Sarkar, S., Davies, J. E., Huang, Z., Tunnacliffe, A., & Rubinsztein, D. C. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609532200 · Cited by 1,142

Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation

Haggarty, S. J., Koeller, K. M., Wong, J. C., Grozinger, C. M., & Schreiber, S. L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0430973100 · Cited by 1,066

Rational Design and Simple Chemistry Yield a Superior, Neuroprotective HDAC6 Inhibitor, Tubastatin A

Butler, K. V., Kalin, J., Brochier, C., Vistoli, G., Langley, B., & Kozikowski, A. P. (2010) · Journal of the American Chemical Society · doi:10.1021/ja102758v · Cited by 801

HDAC6 controls autophagosome maturation essential for ubiquitin‐selective quality‐control autophagy

Lee, J., Koga, H., Kawaguchi, Y., Tang, W., Wong, E., Gao, Y., Pandey, U. B., Kaushik, S., Tresse, E., Lu, J., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2009.405 · Cited by 756

HDAC6 Modulates Cell Motility by Altering the Acetylation Level of Cortactin

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Chemical phylogenetics of histone deacetylases

Bradner, J. E., West, N., Grachan, M. L., Greenberg, E. F., Haggarty, S. J., Warnow, T., & Mazitschek, R. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.313 · Cited by 720

Benefits and pitfalls: Epigenetic modulators in prostate cancer intervention

Upadhyay, N., Tilekar, K. N., Hess, J. D., Pokrovsky, V. S., Aguilera, R. J., & Ramaa, C. S. (2021) · Current Research in Chemical Biology · doi:10.1016/j.crchbi.2021.100006 · Cited by 11

M-134, a novel HDAC6-selective inhibitor, markedly improved arthritic severity in a rodent model of rheumatoid arthritis when combined with tofacitinib

Bae, D., Choi, Y., Lee, J., Ha, N., Suh, D., Baek, J. Y., Park, J., & Son, W. (2020) · Pharmacological Reports · doi:10.1007/s43440-020-00188-x · Cited by 10

Chemical epigenetics to assess the role of HDAC1–3 inhibition in macrophage pro-inflammatory gene expression

Ourailidou, M. E., Leus, N. G. J., Krist, K., Lenoci, A., Mai, A., & Dekker, F. J. (2016) · MedChemComm · doi:10.1039/c6md00375c · Cited by 9

Colon cancer cells evade drug action by enhancing drug metabolism

Cong, B., Thakur, T., Uribe, A. H., Stamou, E., Gopinath, S., Sansom, O. J., Maddocks, O. D. K., & Cagan, R. L. (2025) · Oncogene · doi:10.1038/s41388-025-03472-3 · Cited by 8

Effect of Tubastatin A on the Functional Recovery of Cauda Equina Injury in Rats

Fu, Z., Kong, Q., Wu, Y., Hu, X., & Shi, J. (2018) · World Neurosurgery · doi:10.1016/j.wneu.2018.01.190 · Cited by 8

Déchiffrage du code tubuline

Sadoul, K., Joubert, C., Michallet, S., Nolte, E., Peronne, L., Ramírez‐Ríos, S., Ribba, A., & Lafanéchère, L. (2018) · médecine/sciences · doi:10.1051/medsci/2018295 · Cited by 8

Investigation of non-hydroxamate scaffolds against HDAC6 inhibition: A pharmacophore modeling, molecular docking, and molecular dynamics simulation approach

Zeb, A., Park, C., Son, M., Rampogu, S. D., Alam, S. I., Park, S. J., & Lee, K. W. (2018) · Journal of Bioinformatics and Computational Biology · doi:10.1142/s0219720018400152 · Cited by 7

Amidation inhibitors 4-phenyl-3-butenoic acid and 5-(acetylamino)-4-oxo-6-phenyl-2-hexenoic acid methyl ester are novel HDAC inhibitors with anti-tumorigenic properties

Ali, A., Burns, T. J., Lucrezi, J. D., May, S. W., Green, G. R., & Matesic, D. F. (2015) · Investigational New Drugs · doi:10.1007/s10637-015-0254-2 · Cited by 7

Do biological activities of selective histone deacetylase 6 ( HDAC6 ) inhibitors rely on the modification of cap group?

Liu, X., Wang, S., Shi, X., Lü, M., Wang, C., Li, X., Zhang, Y., Jia, Q., & Liu, H. (2022) · Journal of Molecular Recognition · doi:10.1002/jmr.2988 · Cited by 6

Design and synthesis of novel Hydroxamate and non-Hydroxamate HDAC inhibitors based on Chromone and Quinazolone scaffolds

Ashraf, R., Adel, M., Serya, R. A. T., Ibrahim, E., Haffez, H., Soror, S. H. A., & Abouzid, K. A. M. (2025) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2025.108514 · Cited by 5

Anti-Proliferative Activity of HPOB against Multiple Myeloma Cells via p21 Transcriptional Activation

Liu, L., Sun, X., Xie, Y., Zhuang, Y., Yao, R., & Xu, K. (2018) · Molecules · doi:10.3390/molecules23051044 · Cited by 4

In silico design of HDAC6 inhibitors with neuroprotective effects

Sixto‐López, Y., Gómez-Vidal, J. A., de Pedro, N., Bello, M., Rosales‐Hernández, M. C., & Correa‐Basurto, J. (2021) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2021.2001378 · Cited by 4

Design, synthesis, and biological evaluation of phenylsulfonylfuroxan-β-carboline-hydroxamic acid ternary hybrids for cancer

Gao, C., Wang, W., Yu, Y., & Wu, J. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.118157 · Cited by 3

Histone Deacetylase Inhibitor Entinostat Exerts Anti-NSCLC Effects Through the EGFR Signaling Pathway and MDM2-p53 Axis

He, S., Zhang, A., Sui, C., Zhang, N., Li, M., Li, J., Zhou, S., & Qian, Y. (2026) · Current Pharmaceutical Biotechnology · doi:10.2174/0113892010415089251129072250 · Cited by 3

ACY1215 Exerts Anti-inflammatory Effects by Inhibition of NF-κB and STAT3 Signaling Pathway to Repair Spinal Cord Injury

Dai, C., Wang, X., Liu, R., Gao, W., Zhang, H., Yin, Z., & Ding, Z. (2024) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b23-00603 · Cited by 3

Protein domain movement involved in binding of belinostat and HPOB as inhibitors of histone deacetylase 6 (HDAC6): a hybrid automated-interactive docking study

Iakovou, G., Palmer, L., Ganesan, A., Kitao, A., Laycock, S. D., & Hayward, S. (2025) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-025-00636-x · Cited by 3

Novel antifungal talaroenamine L with unusual leptosphaeronyl moiety from marine-derived Talaromyces sp. HDN17-428 via HDACi elicitation

Anjum, K., Zhou, L., Hayyat, K., Huang, X., Wang, J., Zhang, G., Zhu, T., Che, Q., & Li, D. (2024) · Natural Product Research · doi:10.1080/14786419.2024.2407503 · Cited by 3

Ronald C.D. Breslow (1931–2017): A career in review

Joseph, V., & Levine, M. S. (2021) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2021.104868 · Cited by 3

Inhibitors of the Zinc‐Dependent Histone Deacetylases

Kristensen, H. M. E., Madsen, A. S., & Olsen, C. A. (2019) · Methods and principles in medicinal chemistry · doi:10.1002/9783527809257.ch7 · Cited by 3

Epigenetic modifications control CYP1A1 Inducibility in human and rat keratinocytes

Lin, L.-W., Ehrlich, A. K., & Rice, R. H. (2024) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2024.117163 · Cited by 2

From DMSO to the Anticancer Compound SAHA, an Unusual Intellectual Pathway for Drug Design

Breslow, R. (2016) · Wiley eBooks · doi:10.1002/9783527800315.ch1 · Cited by 2

Combating HIV Latency: A Review of Innovative Interventions and Nanotechnology-Based Formulations

Dubey, D., Fernandes, T., & Singh, P. (2025) · Critical Reviews in Therapeutic Drug Carrier Systems · doi:10.1615/critrevtherdrugcarriersyst.2025054733 · Cited by 1

Epigenetic changes driving therapy resistance in prostate cancer

Doumat, G., Chawareb, E. A., Sebai, T. N., Hout, M., Merhe, A., & Omarzai, Y. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-16032-5.00015-4 · Cited by 1

Phosphorylation and pocket-binding ligands rewire the coupled networks in multidomain protein condensatePreprint

Cao, Y., Chen, J., & Chu, X. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.07.743494 · Cited by 1

REGULATION OF INFLAMMATION, LUNG INJURY AND AUTOPHAGY DURING PSEUDOMONAS AERUGINOSA LUNG INFECTION

Junkins, R. D. (2016) · DalSpace (Dalhousie University)

[Histone deacetylase 6: structure, functions and development of selective inhibitors].

Liu, R., & Fang, H. (2015) · PubMed

Targeting Selective Autophagy of Insoluble Protein Aggregates

Seneci, P. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-801944-3.00005-9

Progress in the Research of Selective Histone deacetylase Inhibitors

张, 立. (2021) · Advances in Material Chemistry · doi:10.12677/amc.2021.91002

Targeting (de)acetylation: A Diversity of Mechanism and Disease

Quaas, C. E., & Long, D. T. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00076-1

Faculty Opinions recommendation of Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials.

Tolar, J., & Thompson, E. A. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.736585207.793566947

Faculty Opinions recommendation of Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials.

Khachigian, L. M. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.736585207.793565997

Faculty Opinions recommendation of Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials.

Anderson, K. S. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.736585207.793570659

Faculty Opinions recommendation of Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials.

Zhang, W., & Porterfield, W. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.736585207.793569236

Faculty Opinions recommendation of Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials.

Walczak, C. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.736585207.793567427

Targeted therapy

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Combinaisons de nouveaux inhibiteurs de désacétylase d’histones 6 avec des inhibiteurs de tyrosine kinase pour le traitement de la leucémie myéloïde chronique

Losson, H. (2020) · theses.fr (ABES) · doi:10.70675/4bf04224zf884z44dfz8928zaff56bbaeb88

Phosphorylation and pocket-binding ligands rewire the coupled networks in multidomain protein condensatePreprint

Cao, Y., Chen, J., & Chu, X. (2026) · eLife · doi:10.7554/elife.112787

Phosphorylation and pocket-binding ligands rewire the coupled networks in multidomain protein condensatePreprint

Cao, Y., Chen, J., & Chu, X. (2026) · eLife · doi:10.7554/elife.112787.1

Reviewer #3 (Public review): Phosphorylation and pocket-binding ligands rewire the coupled networks in multidomain protein condensate

(2026) · eLife · doi:10.7554/elife.112787.1.sa1

BindingDB Entry 50018882: Inside HDACs with more selective HDAC inhibitors.

BindingDB (2024) · UC San Diego · doi:10.7270/q2nk3k9k

BindingDB Entry 50008290: Synthesis and Biological Investigation of Phenothiazine-Based Benzhydroxamic Acids as Selective Histone Deacetylase 6 Inhibitors.

BindingDB (2021) · UC San Diego · doi:10.7270/q2j67mb7

BindingDB Entry 50008716: Selective Inhibition of Histone Deacetylase 10: Hydrogen Bonding to the Gatekeeper Residue is Implicated.

BindingDB (2021) · UC San Diego · doi:10.7270/q26h4mtc

BindingDB Entry 50011516: Recent advances in the discovery of potent and selective HDAC6 inhibitors.

BindingDB (2022) · UC San Diego · doi:10.7270/q25h7kv7

BindingDB Entry 50006907: Discovery of a potent histone deacetylase (HDAC) 3/6 selective dual inhibitor.

BindingDB (2021) · UC San Diego · doi:10.7270/q2zs30t4

BindingDB Entry 50044723: Identification of a novel aminotetralin class of HDAC6 and HDAC8 selective inhibitors.

BindingDB (2016) · UC San Diego · doi:10.7270/q29c700v

BindingDB Entry 50002163: Design, synthesis and evaluate of novel dual FGFR1 and HDAC inhibitors bearing an indazole scaffold.

BindingDB (2020) · UC San Diego · doi:10.7270/q24170pt

BindingDB Entry 50001796: Histone Deacetylase 6-Selective Inhibitors and the Influence of Capping Groups on Hydroxamate-Zinc Denticity.

BindingDB (2020) · UC San Diego · doi:10.7270/q2kp84qw

BindingDB Entry 50007194: Highly fluorescent and HDAC6 selective scriptaid analogues.

BindingDB (2021) · UC San Diego · doi:10.7270/q2jq14bb

BindingDB Entry 50009704: HDAC as onco target: Reviewing the synthetic approaches with SAR study of their inhibitors.

BindingDB (2021) · UC San Diego · doi:10.7270/q2ht2stk

BindingDB Entry 7461: Histone deacetylase 6 structure and molecular basis of catalysis and inhibition

BindingDB (2016) · UC San Diego · doi:10.7270/q2th8kh1

BindingDB Entry 50013580: Identification of novel 1,3-diaryl-1,2,4-triazole-capped histone deacetylase 6 inhibitors with potential anti-gastric cancer activity.

BindingDB (2022) · UC San Diego · doi:10.7270/q2611436

BindingDB Entry 50015587: A Review of Progress in Histone Deacetylase 6 Inhibitors Research: Structural Specificity and Functional Diversity.

BindingDB (2023) · UC San Diego · doi:10.7270/q2g73jp3

BindingDB Entry 50009674: Novel Benzohydroxamate-Based Potent and Selective Histone Deacetylase 6 (HDAC6) Inhibitors Bearing a Pentaheterocyclic Scaffold: Design, Synthesis, and Biological Evaluation.

BindingDB (2021) · UC San Diego · doi:10.7270/q2kp85mz

BindingDB Entry 50016863: Histone deacetylase 6 inhibitors with blood-brain barrier penetration as a potential strategy for CNS-Disorders therapy.

BindingDB (2023) · UC San Diego · doi:10.7270/q2ff3xcc

BindingDB Entry 50000061: Alkoxyurea-Based Histone Deacetylase Inhibitors Increase Cisplatin Potency in Chemoresistant Cancer Cell Lines.

BindingDB (2019) · UC San Diego · doi:10.7270/q2r49swd

BindingDB Entry 50045731: Design and synthesis of orally bioavailable aminopyrrolidinone histone deacetylase 6 inhibitors.

BindingDB (2016) · UC San Diego · doi:10.7270/q2b56mf0

BindingDB Entry 50002433: Design, synthesis, biological evaluation and in vivo testing of dual phosphodiesterase 5 (PDE5) and histone deacetylase 6 (HDAC6)-selective inhibitors for the treatment of Alzheimer's disease.

BindingDB (2020) · UC San Diego · doi:10.7270/q2h134mg

BindingDB Entry 50022374: Tetrahydro-β-carboline derivatives as potent histone deacetylase 6 inhibitors with broad-spectrum antiproliferative activity.

BindingDB (2025) · UC San Diego · doi:10.7270/q2xg9wv6

BindingDB Entry 50021506: Dual inhibitors of HDAC and other epigenetic regulators: A novel strategy for cancer treatment.

BindingDB (2025) · UC San Diego · doi:10.7270/q29k4gvs

BindingDB Entry 50018327: Novel 2, 5-diketopiperazine derivatives as potent selective histone deacetylase 6 inhibitors: Rational design, synthesis and antiproliferative activity.

BindingDB (2024) · UC San Diego · doi:10.7270/q2v98d82

BindingDB Entry 50047160: Discovery of Selective Histone Deacetylase 6 Inhibitors Using the Quinazoline as the Cap for the Treatment of Cancer.

BindingDB (2017) · UC San Diego · doi:10.7270/q2t155h3

BindingDB Entry 50000517: Synthesis and applications of benzohydroxamic acid-based histone deacetylase inhibitors.

BindingDB (2019) · UC San Diego · doi:10.7270/q2g44sqs

Structure-activity relationship and target identification of marine anthranilamides as anti-inflammatory agents

Zhou, Y., Ji, G., Chen, Y., Li, L., Wang, X., Naseer, A., Xue, X., Yang, J., Lu, T., Wang, L., et al. (2026) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2026.119475

Creation of a histone deacetylase 6 inhibitor and its biological effects

Lee, J., Yao, Y., Mahendran, A., Ngo, L., Venta-Perez, G., Choy, M. L., Breslow, R., & Marks, P. A. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1515882112 · Cited by 37

Abstract LB-308: Development of histone deacetylase 6 inhibitors: Effects of HDAC6 inhibitors in normal and cancer cells.

Lee, J., Choy, M. L., Ngo, L., Venta-Perez, G., Mahendran, A., Yao, Y., Breslow, R., & Marks, P. A. (2013) · Cancer Research · doi:10.1158/1538-7445.am2013-lb-308

Design, synthesis and biological evaluation of novel hydroxamic acid based histone deacetylase 6 selective inhibitors bearing phenylpyrazol scaffold as surface recognition motif

Yang, J., Cheng, G., Xu, Q., Luan, S., Wang, S., Liu, D., & Zhao, L. (2017) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2017.08.029 · Cited by 25

The principal pivot : new potent HDAC6 selective inhibitors with a non-hydroxamic acid zinc binding group for applications beyond oncology

Geurs, S. (2022) · Ghent University Academic Bibliography (Ghent University)

Preferential HDAC6 inhibitors derived from HPOB exhibit synergistic antileukemia activity in combination with decitabine

Tretbar, M., Schliehe‐Diecks, J., von Bredow, L., Tan, K., Roatsch, M., Tu, J., Kemkes, M., Sönnichsen, M., Schöler, A., Borkhardt, A., et al. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116447 · Cited by 11