The Zinc-Binding Group Effect: Lessons from Non-Hydroxamic Acid Vorinostat Analogs

Lysine acetylation targets protein complexes and co-regulates major cellular functions

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ACETYLATION AND METHYLATION OF HISTONES AND THEIR POSSIBLE ROLE IN THE REGULATION OF RNA SYNTHESIS

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Erasers of Histone Acetylation: The Histone Deacetylase EnzymesPreprint

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Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders

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A detailed examination of boronic acid–diol complexation

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FDA Approval Summary: Vorinostat for Treatment of Advanced Primary Cutaneous T-Cell Lymphoma

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Epigenetic protein families: a new frontier for drug discovery

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The role of silicon in drug discovery: a review

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Advancements in Hydrazide-Based HDAC Inhibitors: A Review of Recent Developments and Therapeutic Potential

Raucci, A., Zwergel, C., Valente, S., & Mai, A. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c01677 · Cited by 43

Selective and Bioavailable HDAC6 2-(Difluoromethyl)-1,3,4-oxadiazole Substrate Inhibitors and Modeling of Their Bioactivation Mechanism

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Drug Discovery for Histone Deacetylase Inhibition: Past, Present and Future of Zinc-Binding Groups

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Adverse drug reaction profiles of histone deacetylase inhibitors

Begum, R., Parsons, J. L., & Jones, A. M. (2025) · Scientific Reports · doi:10.1038/s41598-025-19717-w · Cited by 23

Next-Generation HDAC Inhibitors: Advancing Zinc-Binding Group Design for Enhanced Cancer Therapy

Hawash, M. (2025) · Cells · doi:10.3390/cells14241997 · Cited by 21

Rational design and optimization of novel 4-methyl quinazoline derivatives as PI3K/HDAC dual inhibitors with benzamide as zinc binding moiety for the treatment of acute myeloid leukemia.

Zhang, K.-H., Huang, R., Ji, M., Lin, S.-W., Lai, F.-F., Wu, D.-Y., Tian, H., Bi, J., Peng, S.-J., Hu, J.-Q., et al. (2023) · European journal of medicinal chemistry · doi:10.1016/j.ejmech.2023.116015 · Cited by 17

Quinazoline‐chalcone hybrids as HDAC/EGFR dual inhibitors: Design, synthesis, mechanistic, and in‐silico studies of potential anticancer activity against multiple myeloma

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Biological function and small molecule inhibitors of histone deacetylase 11

Jia, G., Liu, J., Hou, X., Jiang, Y., & Li, X. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116634 · Cited by 20

Heterocycles–Containing HDAC Inhibitors Active in Cancer: An Overview of the Last Fifteen Years

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Medicinal chemistry advances in targeting class I histone deacetylases

Abdallah, D. I., de Araujo, E. D., Patel, N. H., Hasan, L. S., Moriggl, R., Krämer, O. H., & Gunning, P. T. (2023) · Exploration of Targeted Anti-tumor Therapy · doi:10.37349/etat.2023.00166 · Cited by 17

Design, Synthesis, and Antiproliferative Activity of Novel Indole/1,2,4-Triazole Hybrids as Tubulin Polymerization Inhibitors

Mahmoud, E. D., Abdelhamid, D. S., Mohammed, A. F., Almarhoon, Z. M., Braese, S., Youssif, B. G. M., Hayallah, A. M., & Abdel-Aziz, M. (2025) · Pharmaceuticals · doi:10.3390/ph18020275 · Cited by 15

Histone deacetylase 8 in focus: Decoding structural prerequisites for innovative epigenetic intervention beyond hydroxamates

Khatun, S., Dasgupta, I., Sen, S., Amin, S. A., Qureshi, I. A., Jha, T., & Gayen, S. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.138119 · Cited by 13

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

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Trifluoromethyl quinoline derivative targets inhibiting HDAC1 for promoting the acetylation of histone in cervical cancer cells

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Exploring Derivatives of Quinolizidine Alkaloid Sophoridine in the Design and Biological Mechanistic Evaluation of Histone Deacetylase Inhibitors against Triple‐Negative Breast Cancer

Dai, L., Tan, C., Wang, H., Wang, L., Zhang, T., Zhi, S., Yang, Z., Zhao, X., & Li, D. (2023) · ChemMedChem · doi:10.1002/cmdc.202300467 · Cited by 9

Histone deacetylase (HDAC) inhibitor specificity determinants are preserved in a class of dual HDAC/non-covalent proteasome inhibitors

Chan, A. M., Mitchell, A., Grogan, L., Shapiro, P. S., & Fletcher, S. (2024) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2024.117680 · Cited by 8

Harnessing HDAC-targeted oleanolic acid derivatives for combined anti-cancer and hepatoprotective effects

Gu, Z., Deng, M., Luo, Q., Lin, S., Yu, J., Li, C., Wang, X., Chen, L., Liu, T., Li, Y., et al. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.139761 · Cited by 8

Discovery of organosulfur-based selective HDAC8 inhibitors with anti-neuroblastoma activity

Cho, H., Lee, E., Kim, J., Shin, S., Kim, Y. J., Lee, H., Yu, J. H., Jeon, Y. H., Lee, S. W., Lee, S. Y., et al. (2024) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2024.106921 · Cited by 7

Hydroxamic and poly(hydroxamic acids): A state-of-the-art review of their multifaceted applications

Sunoqrot, R. M., Zainal-Abidin, M. H., Qian, C., & Jamaluddin, N. (2025) · Materials Today Communications · doi:10.1016/j.mtcomm.2025.111751 · Cited by 7

Exploring putative histone deacetylase inhibitors with antiproliferative activity of chrysin derivatives

Kamloon, T., Senawong, T., Senawong, G., Namwan, N., Kumboonma, P., Somsakeesit, L., Ritchumpon, P., Nontakitticharoen, M., Nasomjai, P., & Phaosiri, C. (2025) · Medicinal Chemistry Research · doi:10.1007/s00044-025-03418-0 · Cited by 6

Diversified applications and synthesis of hydroxamic acids

Li, Y., Li, J., Cai, C., Li, Y., Hao, Y., Chen, G., & Bao, X. (2024) · Australian Journal of Chemistry · doi:10.1071/ch24116 · Cited by 5

Replacement of the hydroxamic acid group in the selective HDAC8 inhibitor PCI-34051

Long, K. E., Close, D. A., Johnston, P. A., & Huryn, D. M. (2024) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2024.129810 · Cited by 4

In Cellulo Peptide Cyclization via Gene‐Encoded Proximity‐Induced Proline‐Isothiocyanate Crosslinking

Huang, Z., Jiang, S., Ren, J., Zhao, L., Zhang, Z., Qin, H., Gong, C., & Xuan, W. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202517565 · Cited by 4

Design and synthesis of thiazole-based hydroxamate histone deacetylase inhibitors with potent antitumor efficacy by inducing apoptosis, pyroptosis and cell cycle arrest

Li, Z., Qiu, H., Lu, W., Duan, N., Fan, S., Zhou, R., Li, X., Zhang, H., Liu, N., & Yang, F. (2025) · Scientific Reports · doi:10.1038/s41598-025-08474-5 · Cited by 4

Probing into the plasma stability and microsomal stability of thiol-based prodrug derivatives: Using IYS-15, an HDAC inhibitor as the model thiol

Zhu, L., Wang, Z., Li, Q., Wang, H., & Lei, X. (2025) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2025.118064 · Cited by 3

Recommended Tool Compounds: Isoform- and Class-Specific Histone Deacetylase Inhibitors

Schäker‐Hübner, L., & Hansen, F. K. (2026) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.5c00619 · Cited by 3

Exploring the synthesis, characterization, crystal structures, DFT calculation, hirshfeld surface analysis, and anticancer activity of Ni(II) complex of 1-(4-nitrobenzoyl)-4-phenyl-3-thiosemicarbazide

Pandey, S. K., Chaurasia, R., Shukla, A., Kumari, R., Shekhar, N., Srivastava, A., Acharya, A., Butcher, R. J., & Bharty, M. K. (2024) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2024.140114 · Cited by 3

Computationally Guided Design, Synthesis, and Evaluation of Novel Non-Hydroxamic Histone Deacetylase Inhibitors, Based on N-Trifluoroacetamide as a Zinc-Binding Group, Against Breast Cancer

Morales-Herrejón, G., García-Vázquez, J. B., Fernández–Pomares, C., Bakalara, N., Correa‐Basurto, J., & Mendoza-Figueroa, H. L. (2025) · Pharmaceuticals · doi:10.3390/ph18030351 · Cited by 3

Fair and Square: Design, Synthesis and Biological Evaluations of Squaric Acid Derivatives as Novel HDAC8 Inhibitors

Long, N., Meyer‐Almes, F., Kopranovic, A., & Wren, S. P. (2026) · ChemMedChem · doi:10.1002/cmdc.70270 · Cited by 2

Design, synthesis and evaluation of structural optimization derived HDAC6 isoform-selective inhibitor

Chen, C., Ma, X., Wan, Y., Zhong, Y., Hou, X., Fang, H., & Liang, T. (2025) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2025.108562 · Cited by 2

Screening a library of potential competitive inhibitors against bacterial threonyl-tRNA synthetase: DFT calculations

Aboelnga, M. M., & Gauld, J. W. (2023) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2023.2276878 · Cited by 1

Advances in non-Hydroxamate based Histone Deacetylase Inhibitors as Anticancer Agents

Nabih, N. W., Jaballah, M. Y., Serya, R. A. T., & Abouzid, K. A. M. (2024) · Archives of Pharmaceutical Sciences Ain Shams University · doi:10.21608/aps.2024.274192.1161 · Cited by 1

In Cellulo Peptide Cyclization via Gene‐Encoded Proximity‐Induced Proline‐Isothiocyanate Crosslinking

Huang, Z., Jiang, S., Ren, J., Zhao, L., Zhang, Z., Qin, H., Gong, C., & Xuan, W. (2025) · Angewandte Chemie · doi:10.1002/ange.202517565 · Cited by 1

Esterase-activatable dimeric HDAC inhibitor nanotherapeutics for enhanced lymphoma epigenetic therapy

Li, T., Zhuang, W., Fan, S., Yi, P., Ouyang, G., & Qian, W. (2026) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2026.115416 · Cited by 1

Targeted HDAC8 inhibition with non-hydroxamate [1,2,4]triazolo[4,3-a] quinoline compounds

Bandaru, N. V. M. R., Fathima, A., Sengar, S., Schweipert, M., Chaitanya, K. S., Mohammed, M.-U.-R., Gore, S. T., Trinath, J., Sharma, V., Abbineni, C., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-38490-y · Cited by 1

Harnessing Unique Boron Chemistry to Develop a New Class of Non-hydroxamate HDAC Inhibitors with Validated In Vivo Efficacy

Zhou, L.-Y., Li, Y., Zhang, J.-D., Zhang, X., He, M., Shi, T., Chen, Z., Xiao, Y.-C., & Fen-Er, C. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c03600 · Cited by 1

Zinc Affinity of Benzamide-Based Histone Deacetylase Inhibitors: A DFT Study

Toshev, N., Velichkov, K., Uzunova, Y. I., Cheshmedzhieva, D., & Dudev, T. (2026) · Molecules · doi:10.3390/molecules31101650 · Cited by 1

Structure-Guided Discovery of a Nonpeptidic MT5-MMP Inhibitor

Magniez, A., Giovannini, J., Zipfel, P., Rémondin, C., Saïdoun, H., Davis, A., Rivera, S., Dallemagne, P., Rochais, C., & Lepailleur, A. (2026) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.6c00219 · Cited by 1

Targeted Protein Degradation of Metalloenzymes

O’Herin, C., & Cohen, S. M. (2025) · Wiley eBooks · doi:10.1002/0471266949.bmc303

Establishing a noncanonical zinc-binding group as a selective histone deacetylase inhibitor and possible novel anticancer agent.

Huang, H.-C., Chen, T.-Y., Yeh, T.-Y., Yu, M., Wu, S.-S., Li, G.-Y., Chen, B.-J., Lin, M.-H., Lin, C., Hsu, J.-L., et al. (2025) · Bioorganic chemistry (Print) · doi:10.1016/j.bioorg.2025.108917

In silico discovery and biological evaluation of a novel selective HDAC8 inhibitor featuring 1H-pyrazolo[3,4-b]pyridine scaffold

Yan, W., Shi, H., Li, T., Fu, Y. H. H., Zhang, Y. F., Zhang, Y., Liu, J., & Li, X. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2026.109660

Discovery of a Covalent HDAC3 Degrader with Excellent Anti-Inflammatory Activity and NLRP3 Inflammasome Suppression

Qin, H., Shi, Y., Liu, R., Wang, B., Guo, L., Hao, G., Zhang, G., Liu, D., Zhao, L., & Huang, M. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c02513

Synthesis and in vitro antitumor evaluation of novel 3,4-dihydropyrimidinone-vorinostat hybrids against gastric and breast cancer cell lines

Rios, E. A. M., Pereira, G. M. S. D. M., D’Oca, M. G. M., Dea, C. M., dos Santos, E. R. F. B., Rampon, D. S., Santos, L. S., Nachtigall, F. M., Guzmán, L., Moore‐Carrasco, R., et al. (2026) · RSC Advances · doi:10.1039/d6ra00701e

Wavelength-tunable light regulates binding affinity of histone deacetylase inhibitors via azobenzene Photoswitches

Ru, Y., Guo, S., He, Y., Huang, X., Zhang, Z., Shi, L., Shao, X., Li, Z., Fu, W., & Shao, X. (2026) · Pesticide Biochemistry and Physiology · doi:10.1016/j.pestbp.2026.107154

Turning the Sulfur Dial: Strategic Oxidation-State Manipulation in Modern Drug Discovery

Arshad, A. S. M., Singh, R., & Wiemer, A. J. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c01226

Exploration of non-hydroxamate based quinoline analogues as HDAC8 inhibitors

Bandaru, N. V. M. R., Joshi, V., Schweipert, M., Chaitanya, K. S., Sen, D., Mohammed, M.-U.-R., Sharma, V., Abbineni, C., Meyer‐Almes, F., & Sekhar, K. V. G. C. (2026) · RSC Advances · doi:10.1039/d6ra06186a

Targeting the Zinc Metalloproteinase Superfamily in the CNS: Medicinal Chemistry Strategies To Optimize Selectivity, Pharmacokinetics, and Blood–Brain Barrier Permeability

Nagashima, Y. (2026) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6c00496

Discovery of cyanocarbonimidodithioates as novel non-hydroxamate zinc-binding groups for selective HDAC8 inhibition: Design, synthesis, biological evaluation, anticancer activity, and in silico studies

Chaitanya, K. S., Chaudhari, H., Fathima, A., Sengar, S., Schweipert, M., Khetmalis, Y. M., Bandaru, N. V. M. R., Abbineni, C., Trinath, J., Sharma, V., et al. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2026.110551

Toward Tumor-Conditional Release of Histone Deacetylase Inhibitors from Nongenotoxic Drug Conjugates

Muir, R. K., Gonciarz, R. L., Steri, V., Blank, B. R., Hahn, B., & Renslo, A. R. (2026) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.6c00312

Discovery of Thiazolamide-based PI4KIIIβ/HDAC Dual Inhibitors with Potent Activity against Hepatitis C Virus

Wang, E., Xue, Y., Jia, S., 陈, 士., Gao, Y., Hu, Q., Han, F., Ruan, X.-Q., Chen, M., Guo, M., et al. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c01344

BindingDB Entry 50021859: Replacement of the hydroxamic acid group in the selective HDAC8 inhibitor PCI-34051.

BindingDB (2025) · UC San Diego · doi:10.7270/q2xs612h

BindingDB Entry 50021347: Preferential HDAC6 inhibitors derived from HPOB exhibit synergistic antileukemia activity in combination with decitabine.

BindingDB (2025) · UC San Diego · doi:10.7270/q2ng4w86

BindingDB Entry 50003811: Biological function and small molecule inhibitors of histone deacetylase 11.

BindingDB (2026) · UC San Diego · doi:10.7270/q2b85dzw

BindingDB Entry 50020470: Selective and Bioavailable HDAC6 2-(Difluoromethyl)-1,3,4-oxadiazole Substrate Inhibitors and Modeling of Their Bioactivation Mechanism.

BindingDB (2024) · UC San Diego · doi:10.7270/q21z48vm

BindingDB Entry 50023728: The role of silicon in drug discovery: a review.

BindingDB (2026) · UC San Diego · doi:10.7270/q2zp4c25

BindingDB Entry 50021594: Rational design and optimization of novel 4-methyl quinazoline derivatives as PI3K/HDAC dual inhibitors with benzamide as zinc binding moiety for the treatment of acute myeloid leukemia.

BindingDB (2025) · UC San Diego · doi:10.7270/q24j0ksq

BindingDB Entry 50021778: Histone deacetylase (HDAC) inhibitor specificity determinants are preserved in a class of dual HDAC/non-covalent proteasome inhibitors.

BindingDB (2025) · UC San Diego · doi:10.7270/q2qj7nzq

Discovery of Novel HDAC8 Inhibitors Through Shape-Based Virtual Screening: Experimental Validation and Characterization of a Promising Quinoline-Based Hit Scaffold

Gargano, A., González‐Bakker, A., Puerta, A., Maggisano, V., Bulotta, S., Rocca, R., Padrón, J. M., & Alcaro, S. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27219557

Non-Hydroxamate Zinc-Binding Groups as Warheads for Histone Deacetylases

Frühauf, A., & Meyer‐Almes, F. (2021) · Molecules · doi:10.3390/molecules26175151 · Cited by 58

Zinc binding groups for histone deacetylase inhibitors

Zhang, L., Zhang, J., Jiang, Q., Zhang, L., & Song, W. (2018) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2017.1417274 · Cited by 240

Drug Discovery for Histone Deacetylase Inhibition: Past, Present and Future of Zinc-Binding Groups

Pires, G. S., Tolomeu, H. V., Rodrigues, D. A., Lima, L. M., Fraga, C. A. M., & Pinheiro, P. D. S. M. (2025) · Pharmaceuticals · doi:10.3390/ph18040577 · Cited by 28

Next-Generation HDAC Inhibitors: Advancing Zinc-Binding Group Design for Enhanced Cancer Therapy

Hawash, M. (2025) · Cells · doi:10.3390/cells14241997 · Cited by 21

Zinc-dependent Deacetylase (HDAC) Inhibitors with Different Zinc Binding Groups

Li, Y., Wang, F., Chen, X., Wang, J., Zhao, Y., Li, Y., & He, B. (2019) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026619666190122144949 · Cited by 80