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; Jakubikova, J; Munshi, N C; Haggarty, S J; Richardson, P G; Hideshima, T; Anderson, K C

doi:10.1038/leu.2013.231

Cited by 159Histone Deacetylase Inhibitors ResearchMultiple Myeloma Research and TreatmentsProtease and Inhibitor Mechanisms

Histone deacetylase 3 as a novel therapeutic target in multiple myeloma

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Minami, J, Suzuki, R, Mazitschek, R, Gorgun, G, Ghosh, B, Cirstea, D, Hu, Y, Mimura, N +8 more·2014·Leukemia

DOI 10.1038/leu.2013.231PMC PMC4165599

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Abstract

Histone deacetylases (HDACs) represent novel molecular targets for the treatment of various types of cancers, including multiple myeloma (MM). Many HDAC inhibitors have already shown remarkable antitumor activities in the preclinical setting; however, their clinical utility is limited because of unfavorable toxicities associated with their broad range HDAC inhibitory effects. Isoform-selective HDAC inhibition may allow for MM cytotoxicity without attendant side effects. In this study, we demonstrated that HDAC3 knockdown and a small-molecule HDAC3 inhibitor BG45 trigger significant MM cell growth inhibition via apoptosis, evidenced by caspase and poly (ADP-ribose) polymerase cleavage. Importantly, HDAC3 inhibition downregulates phosphorylation (tyrosine 705 and serine 727) of signal transducers and activators of transcription 3 (STAT3). Neither interleukin-6 nor bone marrow stromal cells overcome this inhibitory effect of HDAC3 inhibition on phospho-STAT3 and MM cell growth. Moreover, HDAC3 inhibition also triggers hyperacetylation of STAT3, suggesting crosstalk signaling between phosphorylation and acetylation of STAT3. Importantly, inhibition of HDAC3, but not HDAC1 or 2, significantly enhances bortezomib-induced cytotoxicity. Finally, we confirm that BG45 alone and in combination with bortezomib trigger significant tumor growth inhibition in vivo in a murine xenograft model of human MM. Our results indicate that HDAC3 represents a promising therapeutic target, and validate a prototype novel HDAC3 inhibitor BG45 in MM.

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Mocetinostat gains selectivity for HDAC1/2 against HDAC3 (5.5-10.7 fold selective) without resorting to the use of an FT substituent.
“Finally, an example of the importance of the cap group is highlighted in mocetinostat (Figure 10), where selectivity is gained for HDAC1/2 against HDAC3 (5.5–10.7 fold selective) without resorting to the use of an FT substituent [64].”
From Medicinal chemistry advances in targeting class I histone deacetylases (2023) · cites this paper as [64]
The Introduction identifies mocetinostat as an amino-benzamide inhibitor highly specific for HDAC1, HDAC2, and HDAC3. It does not report 5.5–10.7-fold selectivity for HDAC1/2 over HDAC3 or attribute that selectivity to the cap group or the absence of an FT substituent. (LLM, conf=0.82)
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Transcriptional repression by the HDAC4–RelB–p52 complex regulates multiple myeloma survival and growth
Vallabhapurapu, S., Noothi, S. K., Pullum, D. A., Lawrie, C. H., Pallapati, R. R., Potluri, V., Kuntzen, C., Khan, S., Plas, D. R., Orlowski, R. Z., et al. (2015) · Nature Communications · doi:10.1038/ncomms9428 · Cited by 61 · see citing works
Pracinostat (SB939), a histone deacetylase inhibitor, suppresses breast cancer metastasis and growth by inactivating the IL-6/STAT3 signalling pathways
Chen, J., Li, N., Liu, B., Ling, J., Yang, W., Pang, X., & Li, T. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117469 · Cited by 65 · see citing works
Selective HDAC3 Inhibitors with Potent In Vivo Antitumor Efficacy against Triple-Negative Breast Cancer
Pulya, S., Himaja, A., Paul, M., Adhikari, N., Banerjee, S., Routholla, G., Biswas, S., Jha, T., & Ghosh, B. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00614 · Cited by 63 · see citing works
Self-citation
Potent and Selective Inhibitors of Histone Deacetylase-3 Containing Chiral Oxazoline Capping Groups and a N -(2-Aminophenyl)-benzamide Binding Unit
Marson, C. M., Matthews, C. J., Atkinson, S. J., Lamadema, N., & Thomas, N. S. B. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00545 · Cited by 58 · see citing works
Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway
Wang, H., Liu, Y.-C., Zhu, C.-Y., Yan, F., Wang, M.-Z., Chen, X., Wang, X.-K., Pang, B., Li, Y.-H., Liu, D.-H., et al. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01792-8 · Cited by 57 · see citing works
Design, synthesis and biological screening of 2-aminobenzamides as selective HDAC3 inhibitors with promising anticancer effects
Trivedi, P., Adhikari, N., Amin, S. A., Jha, T., & Ghosh, B. (2018) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2018.08.030 · Cited by 64 · see citing works
“Moreover, it was also found to be effective in vivo in arresting tumor growth as evidenced in the murine xenograft model of multiple myeloma (Minami et al., 2014).”
BackgroundSelf-citation
Synthesis, Molecular Docking and Biological Characterization of Pyrazine Linked 2-Aminobenzamides as New Class I Selective Histone Deacetylase (HDAC) Inhibitors with Anti-Leukemic Activity
Ibrahim, H. S., Abdelsalam, M., Zeyn, Y., Zessin, M., Mustafa, A.-H. M., Fischer, M. A., Zeyen, P., Sun, P., Bülbül, E. F., Vecchio, A., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010369 · Cited by 50 · see citing works
“The HDAC1 (PDB ID: 4BKX) in apo-form and HDAC3 (PDB ID: 4A69) in apo-form were minimized with the ligand of HDAC2 (PDB ID: 4LY1) and BG45 molecules [59], respectively.”
Background
Programmed cell death 5 mediates HDAC3 decay to promote genotoxic stress response
Choi, H.-K., Choi, Y., Park, E. S., Park, S.-Y., Lee, S.-H., Seo, J., Jeong, M.-H., Jeong, J., Cheong, J., Lee, P. C. W., et al. (2015) · Nature Communications · doi:10.1038/ncomms8390 · Cited by 49 · see citing works
Efficient Synthesis and Bioevaluation of Novel Dual Tubulin/Histone Deacetylase 3 Inhibitors as Potential Anticancer Agents
Peng, X., Chen, J., Li, L., Sun, Z., Liu, J., Ren, Y., Huang, J., & Chen, J. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00413 · Cited by 71 · see citing works
Epigenetic Aberrations in Multiple Myeloma
Caprio, C., Sacco, A., Giustini, V., & Roccaro, A. M. (2020) · Cancers · doi:10.3390/cancers12102996 · Cited by 48 · 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
Self-citation
The biological significance of histone modifiers in multiple myeloma: clinical applications
Ohguchi, H., Hideshima, T., & Anderson, K. C. (2018) · Blood Cancer Journal · doi:10.1038/s41408-018-0119-y · Cited by 46 · see citing works
Self-citation
HDAC6 Inhibitors Modulate Lys49 Acetylation and Membrane Localization of β-Catenin in Human iPSC-Derived Neuronal Cells
Iaconelli, J., Huang, J., Berkovitch, S. S., Chattopadhyay, S., Mazitschek, R., Schreiber, S. L., Haggarty, S. J., & Karmacharya, R. (2014) · ACS Chemical Biology · doi:10.1021/cb500838r · Cited by 45 · see citing works
Self-citation
Chidamide: Targeting epigenetic regulation in the treatment of hematological malignancy
Cao, H., Li, L., Xue, S., & Dai, H. (2022) · Hematological Oncology · doi:10.1002/hon.3088 · Cited by 47 · see citing works
Implication for Cancer Stem Cells in Solid Cancer Chemo-Resistance: Promising Therapeutic Strategies Based on the Use of HDAC Inhibitors
Roca, M. S., Gennaro, E. D., & Budillon, A. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8070912 · Cited by 45 · see citing works
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 45 · see citing works
Design, synthesis and biological evaluation of 2-(3,4-dimethoxyphenyl)-6 (1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-a]pyridine analogues as antiproliferative agents
Chitti, S., Srinivasarao, S., Reddy, P. S. K., Trivedi, P., Bobde, Y., Kumar, C., Rangan, K., Ghosh, B., & Sekhar, K. V. G. C. (2019) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2019.08.013 · Cited by 48 · see citing works
Self-citation
The role of acetylation and deacetylation in cancer metabolism
Wang, C., & Ma, X. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70145 · Cited by 31 · see citing works
“107”
DNMTi/HDACi combined epigenetic targeted treatment induces reprogramming of myeloma cells in the direction of normal plasma cells
Bruyer, A., Maes, K., Herviou, L., Kassambara, A., Seckinger, A., Cartron, G., Reme, T. X., Robert, N., Requirand, G., Boireau, S., et al. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0025-x · Cited by 46 · see citing works
Downregulation of Ca2+-Activated Cl− Channel TMEM16A by the Inhibition of Histone Deacetylase in TMEM16A-Expressing Cancer Cells
Matsuba, S., Niwa, S., Muraki, K., Kanatsuka, S., Nakazono, Y., Hatano, N., Fujii, M., Zhan, P., Suzuki, T., & Ohya, S. (2014) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.217315 · Cited by 40 · see citing works
Synthesis, biological evaluation, and molecular docking analysis of novel linker-less benzamide based potent and selective HDAC3 inhibitors
Routholla, G., Pulya, S., Patel, T., Abdul Amin, S., Adhikari, N., Biswas, S., Jha, T., & Ghosh, B. (2021) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2021.105050 · Cited by 39 · see citing works
Self-citation
Overview of class I HDAC modulators: Inhibitors and degraders
Huang, Z., Zeng, L., Cheng, B., & Li, D. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116696 · Cited by 34 · see citing works
Design, synthesis, biological evaluation and molecular docking study of arylcarboxamido piperidine and piperazine-based hydroxamates as potential HDAC8 inhibitors with promising anticancer activity
Trivedi, P., Adhikari, N., Amin, S. A., Bobde, Y., Routholla, G., Jha, T., & Ghosh, B. (2019) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2019.105046 · Cited by 45 · see citing works
Self-citation
Upregulation of AKAP12 with HDAC3 depletion suppresses the progression and migration of colorectal cancer
He, P., Li, K., Li, S.-B., Hu, T., Guan, M., Sun, F., & Liu, W.-W. (2018) · International Journal of Oncology · doi:10.3892/ijo.2018.4284 · Cited by 35 · see citing works
“Other data have also shown that HDAC3 modulates the JAK/STAT3 pathway in multiple myeloma cells (34).”
Result
HDAC3 Inhibitor RGFP966 Ameliorated Neuroinflammation in the Cuprizone-Induced Demyelinating Mouse Model and LPS-Stimulated BV2 Cells by Downregulating the P2X7R/STAT3/NF-κB65/NLRP3 Activation
Sun, W., Zhang, N., Liu, B., Yang, J., Loers, G., Siebert, H., Wen, M., Zheng, X., Wang, Z., Han, J., et al. (2022) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00826 · Cited by 41 · see citing works
Histone deacetylase 3 inhibitors in learning and memory processes with special emphasis on benzamides
Amin, S. A., Adhikari, N., Kotagiri, S., Jha, T., & Ghosh, B. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.01.077 · Cited by 44 · see citing works
Self-citation
Downregulation of HDAC3 by ginsenoside Rg3 inhibits epithelial–mesenchymal transition of cutaneous squamous cell carcinoma through c‐Jun acetylation
Zhang, L., Shan, X., Chen, Q., Xu, D., Fan, X., Yu, M., Yan, Q., & Liu, J. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28788 · Cited by 32 · see citing works
The STAT3 inhibitor WP1066 reverses the resistance of chronic lymphocytic leukemia cells to histone deacetylase inhibitors induced by interleukin-6.
Lu, K., Fang, X., Feng, L.-L., Jiang, Y.-J., Zhou, X., Liu, X., Li, P., Chen, N., Ding, M., Wang, N., et al. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.01.021 · Cited by 31 · see citing works
HDAC6 Modulates Signaling Pathways Relevant to Synaptic Biology and Neuronal Differentiation in Human Stem Cell-Derived Neurons
Iaconelli, J., Xuan, L. L., & Karmacharya, R. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071605 · Cited by 37 · see citing works
Recent advancement of HDAC inhibitors against breast cancer
Mehmood, S. A., Sahu, K. K., Sengupta, S., Partap, S., Karpoormath, R. V., Kumar, B., & Kumar, D. (2023) · Medical Oncology · doi:10.1007/s12032-023-02058-x · Cited by 33 · see citing works
“The deacetylation of lysine residues, which is associated with compacted chromatin, is known to impede transcription of the genes that are located in that region [83, 84].”
Background
Histone deacetylase inhibitor BG45-mediated HO-1 expression induces apoptosis of multiple myeloma cells by the JAK2/STAT3 pathway
Tang, S., Cheng, B.-Q., Zhe, N., Ma, D., Xu, J.-B., Li, X.-Y., Guo, Y., Wu, W.-B., & Wang, J.-S. (2018) · Anti-Cancer Drugs · doi:10.1097/cad.0000000000000568 · Cited by 28 · see citing works
Low levels of pyruvate induced by a positive feedback loop protects cholangiocarcinoma cells from apoptosis
Zhang, M., Pan, Y., Tang, D., Dorfman, R. G., Xu, L., Zhou, Q., Zhou, L., Wang, Y., Yang, L., Yin, Y., et al. (2019) · Cell Communication and Signaling · doi:10.1186/s12964-019-0332-8 · Cited by 28 · see citing works
Therapeutic effects of the novel subtype-selective histone deacetylase inhibitor chidamide on myeloma-associated bone disease
He, J., Chen, Q., Gu, H., Chen, J., Zhang, E., Guo, X., Huang, X., Yan, H., He, D., Yang, Y., et al. (2018) · Haematologica · doi:10.3324/haematol.2017.181172 · Cited by 29 · see citing works
Targeting histone deacetylase 3 (HDAC3) in the bone marrow microenvironment inhibits multiple myeloma proliferation by modulating exosomes and IL-6 trans-signaling
Ho, M., Chen, T., Liu, J., Dowling, P., Hideshima, T., Zhang, L., Morelli, E., Camci‐Unal, G., Wu, X., Tai, Y., et al. (2019) · Leukemia · doi:10.1038/s41375-019-0493-x · Cited by 74 · see citing works
Self-citation
Histone Deacetylase 3 Deletion in Mesenchymal Progenitor Cells Hinders Long Bone Development
Feigenson, M., Shull, L. C., Taylor, E. L., Camilleri, E. T., Riester, S. M., van Wijnen, A. J., Bradley, E. W., & Westendorf, J. J. (2017) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3236 · Cited by 28 · see citing works
The discovery of novel HDAC3 inhibitors via virtual screening and <i>in vitro</i> bioassay
Xia, J., Hu, H., Xue, W., Wang, X. S., & Wu, S. (2018) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2018.1437156 · Cited by 24 · see citing works
Histone deacetylases inhibitors: conjugation to other anti-tumour pharmacophores provides novel tools for cancer treatment
Papavassiliou, K. A., & Papavassiliou, A. G. (2013) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2014.857401 · Cited by 26 · see citing works
“Isoform-selective HDACi may provide a better clinical benefit than pan-HDACi, while reducing or eliminating undesirable effects [2-5].”
Background
The Role of Epigenetics in the Development and Progression of Multiple Myeloma
Ismail, N. H., Mussa, A., Zakaria, N. A., Al-Khreisat, M. J., Zahidin, M. A., Ramli, N. N., Mohammad, S. N. N. A., Hassan, R., Mohd Noor, N. H., Iberahim, S., et al. (2022) · Biomedicines · doi:10.3390/biomedicines10112767 · Cited by 22 · see citing works
Targeted therapy for multiple myeloma: an overview on CD138-based strategies
Riccardi, F., Tangredi, C., Bo, M. D., & Toffoli, G. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1370854 · Cited by 22 · see citing works
“Similarly, histone acetylation modi ﬁ ers have been found to have carcinogenic signi ﬁ cance as they are involved in cell proliferation, survival and apoptosis (84 – 86).”
Background
Contribution of the bone marrow stromal cells in mediating drug resistance in hematopoietic tumors
Chen, W.-C., Hu, G., & Hazlehurst, L. (2020) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2020.08.006 · Cited by 24 · see citing works
“Remarkably, romidepsin treatment decreases the expression of CD49d, a key component of the VAL-4 integrin that mediates the MM adhesion to stromal cells [71].”
Background
Epigenetic marvels: exploring the landscape of colorectal cancer treatment through cutting-edge epigenetic-based drug strategies
Tahghighi, A., Seyedhashemi, E., Mohammadi, J., Moradi, A., Esmaeili, A., Pornour, M., Jafarifar, K., & Ganji, S. M. (2025) · Clinical Epigenetics · doi:10.1186/s13148-025-01844-w · Cited by 21 · see citing works
“Benzamides like mocetinostat and entinostat are generally effective against class I HDACs [88].”
Selective Targeting of Class I HDAC Reduces Microglial Inflammation in the Entorhinal Cortex of Young APP/PS1 Mice
Wang, C., Shen, D., Hu, Y., Chen, J., Liu, J., Huang, Y., Yu, X., Chu, H., Zhang, C., Yin, L., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054805 · Cited by 27 · see citing works
“It also inhibits HDAC1 and HDAC2 with reduced potency [31].”
BackgroundSelf-citation
Prothymosin α promotes colorectal carcinoma chemoresistance through inducing lipid droplet accumulation
Jin, L., Zhu, L., Pan, Y., Fu, H., & Zhang, J. (2021) · Mitochondrion · doi:10.1016/j.mito.2021.04.001 · Cited by 23 · see citing works
Designing potential HDAC3 inhibitors to improve memory and learning
Amin, S. A., Adhikari, N., Jha, T., & Ghosh, B. (2018) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2018.1477625 · Cited by 27 · see citing works
Self-citation
Post-translational modification of CDK1–STAT3 signaling by fisetin suppresses pancreatic cancer stem cell properties
Xu, X., Ding, Y., Jin, J., Xu, C., Hu, W., Wu, S., Ding, G., Cheng, R., Cao, L., & Jia, S. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-01118-z · Cited by 23 · see citing works
“Because HDAC3 has been reported to regulate the phosphorylation of STAT3 Y705 in other cancer types [23, 24], we speculated that HDAC3 might influence the phosphorylation of STAT3 Y705 via activation of CDK1.”
Background
Docking, Binding Free Energy Calculations and In Vitro Characterization of Pyrazine Linked 2-Aminobenzamides as Novel Class I Histone Deacetylase (HDAC) Inhibitors
Bülbül, E. F., Melesina, J., Ibrahim, H. S., Abdelsalam, M. A. M., Vecchio, A., Robaa, D., Zessin, M., Schutkowski, M., & Sippl, W. (2022) · Molecules · doi:10.3390/molecules27082526 · Cited by 17 · see citing works
“Then, protein–ligand complexes were minimized using the OPLS3e force-field to remove steric clashes [37].”
Method
Lenalidomide and vorinostat maintenance after autologous transplant in multiple myeloma
Sborov, D. W., Benson, D. M., Williams, N., Huang, Y., Bowers, M. A., Humphries, K., Efebera, Y. A., Devine, S. M., & Hofmeister, C. C. (2015) · British Journal of Haematology · doi:10.1111/bjh.13527 · Cited by 20 · see citing works
Novel hydroxamic acid derivative induces apoptosis and constrains autophagy in leukemic cells
Fischer, M. A., Mustafa, A. M., Hausmann, K., Ashry, R., Kansy, A. G., Liebl, M. C., Brachetti, C., Piée‐Staffa, A., Zessin, M., Ibrahim, H. S., et al. (2023) · Journal of Advanced Research · doi:10.1016/j.jare.2023.07.005 · Cited by 24 · see citing works
Bone Marrow Stroma-Induced Transcriptome and Regulome Signatures of Multiple Myeloma
Dziadowicz, S. A., Wang, L., Akhter, H., Aesoph, D., Sharma, T., Adjeroh, D., Hazlehurst, L., & Hu, G. (2022) · Cancers · doi:10.3390/cancers14040927 · Cited by 33 · see citing works
“Quinoline Consists of 1 H ‐1,2,3‐Triazole Hybrids: Design, Synthesis and Anticancer Evaluation”
Venkata, S. P. R. M., C.Narkhede, U., Jadhav, V., Naidu, C. G., Addada, R. R., Pulya, S., & Ghosh, B. (2019) · doi:10.1002/slct.201903938 · Cited by 19
Self-citation
HDAC3 as an Emerging Therapeutic Target for Alzheimer's Disease and other Neurological Disorders
Li, Y., Izhar, T., & Kanekiyo, T. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04866-w · Cited by 19 · see citing works
“Both BG-45 and PT3 are benzamide class HDAC3 inhibitors [30, 31], but are less HDAC3 selective when compared to RGFP966 and BRD3308 (Table 1).”
RGFP966, a histone deacetylase 3 inhibitor, promotes glioma stem cell differentiation by blocking TGF-β signaling via SMAD7
Liang, H., Wang, Q., Wang, D., Zheng, H., Kalvakolanu, D. V., Lu, H., Wen, N., Chen, X., Xu, L., Ren, J., et al. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.114118 · Cited by 18 · see citing works
An epigenetic view of B‐cell disorders
Alberghini, F., Petrocelli, V., Rahmat, M., & Casola, S. S. (2015) · Immunology and Cell Biology · doi:10.1038/icb.2014.116 · Cited by 14 · see citing works
Induction of differential apoptotic pathways in multiple myeloma cells by class-selective histone deacetylase inhibitors
Hideshima, T., Mazitschek, R., Santo, L., Mimura, N., Görgün, G., Richardson, P. G. G., Raje, N. S., & Anderson, K. C. (2013) · Leukemia · doi:10.1038/leu.2013.301 · Cited by 16 · see citing works
Self-citation
Targeting transcription factors in multiple myeloma: evolving therapeutic strategies
Li, S., Vallet, S., Sacco, A., Roccaro, A. M., Lentzsch, S., & Podar, K. (2019) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2019.1605354 · Cited by 18 · see citing works
“Conversely, inhibition of HDAC3 by genetic knockdown or by the selective inhibitor BG45 abrogates MM cell proliferation [135].”
Background
HDAC and Ku70 axis- an effective target for apoptosis induction by a new 2-cyano-3-oxo-1,9-dien glycyrrhetinic acid analogue
Gong, P., Li, K., Li, Y., Liu, D., Zhao, L., & Jing, Y. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0602-1 · Cited by 19 · see citing works
Epigenetic actions of environmental factors and promising drugs for cancer therapy (Review)
Bai, Z., Bai, B., Zhu, J., Di, C., Li, X., & Zhou, W. (2017) · Oncology Letters · doi:10.3892/ol.2017.7597 · Cited by 11 · see citing works
“A previous study revealed that HDACs serve roles as crucial mediators in tumor survival and progression (43).”
Use of the 46/1 haplotype to model JAK2V617F clonal architecture in PV patients: clonal evolution and impact of IFNα treatment
Hasan, S., Cassinat, B., Droin, N., Couédic, J. L., Favale, F., Monte-Mór, B., Lacout, C., Fontenay, M., Dosquet, C., Chomienne, C., et al. (2014) · Leukemia · doi:10.1038/leu.2013.303 · Cited by 17
Exploring the impact of trifluoromethyl (–CF3) functional group on the anti-cancer activity of isoxazole-based molecules: design, synthesis, biological evaluation and molecular docking analysis
Pattanayak, P., Nikhitha, S., Halder, D., Ghosh, B., & Chatterjee, T. (2024) · RSC Advances · doi:10.1039/d4ra02856b · Cited by 16
Self-citation
Upregulation of Bone Morphogenetic Protein-2 Synthesis and Consequent Collagen II Expression in Leptin-stimulated Human Chondrocytes
Chang, S.-F., Hsieh, R.-Z., Huang, K.-C., Chang, C. A., Chiu, F.-Y., Kuo, H.-C., Chen, C.-N., & Su, Y.-P. (2015) · PLoS ONE · doi:10.1371/journal.pone.0144252 · Cited by 16
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 15 · see citing works
“Finally, a cap-less inhibitor, BG45, bears a pyrazine linker, which allows for faster kinetics of binding to the target protein due to the rigidity of the molecule and lack of degrees of freedom that comes with a cap group [65].”
Background
A ‘click’ chemistry approach to novel entinostat (MS-275) based class I histone deacetylase proteolysis targeting chimeras
Cross, J. M., Coulson, M. E., Smalley, J. P., Pytel, W. A., Ismail, O., Trory, J. S., Cowley, S. M., & Hodgkinson, J. T. (2022) · RSC Medicinal Chemistry · doi:10.1039/d2md00199c · Cited by 27 · see citing works
Emerging small molecule approaches to enhance the antimyeloma benefit of proteasome inhibitors
Driscoll, J. J., & Brailey, M. (2017) · Cancer and Metastasis Reviews · doi:10.1007/s10555-017-9698-5 · Cited by 16 · see citing works
Down-regulation of HDAC3 inhibits growth of cholangiocarcinoma by inducing apoptosis
Zhang, M., Yin, Y., Dorfman, R. G., Zou, T., Pan, Y., Li, Y., Wang, Y., Zhou, Q., Zhou, L., Kong, B., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.19660 · Cited by 18 · see citing works
Coregulator profiling of the glucocorticoid receptor in lymphoid malignancies
Clarisse, D., Thommis, J., Wesemael, K. V., Houtman, R., Ratman, D., Tavernier, J. H., Offner, F. C., Beck, I. M. E., & Bosscher, K. D. (2017) · Oncotarget · doi:10.18632/oncotarget.22764 · Cited by 14 · see citing works
Epigenetic Approaches to Overcome Fluoropyrimidines Resistance in Solid Tumors
Grumetti, L., Lombardi, R., Iannelli, F., Pucci, B., Avallone, A., Gennaro, E. D., & Budillon, A. (2022) · Cancers · doi:10.3390/cancers14030695 · Cited by 16 · see citing works
Design, synthesis, and biological evaluation of novel nicotinamide derivatives as potential histone deacetylase-3 inhibitors
Hamoud, M. M. S., Pulya, S., Osman, N. A., Bobde, Y., Hassan, A. E. A., Abdel‐Fattah, H. A., Ghosh, B., & Ghanim, A. M. (2020) · New Journal of Chemistry · doi:10.1039/d0nj01274b · Cited by 25 · see citing works
Self-citation
Lycorine induces cell death in MM by suppressing Janus Kinase/signal transducer and activator of transcription via inducing the expression of SOCS1.
Jin, Z., Zhou, S.-J., Zhang, Y., Ye, H.-G., Jiang, S.-F., Yu, K., & Ma, Y.-Y. (2016) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2016.10.069 · Cited by 13
Piperidine-containing drugs and recently studied analogs – biological activity, mechanism of action and synthetic cascade access to their scaffolds
Łowicki, D., & Przybylski, P. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.118213 · Cited by 14 · see citing works
Design and synthesis of pyridine-based benzamides as potent HDAC3 inhibitors as an armament against breast cancer with in vivo validation
Himaja, A., Routholla, G., Patel, T. K., Banerjee, S., Begum, D., Regula, S., Pulya, S., Biswas, S., Adhikari, N., & Ghosh, B. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.117636 · Cited by 11 · see citing works
Self-citation

Authors: Minami, J., Suzuki, R., Mazitschek, R., Gorgun, G., Ghosh, B., Cirstea, D., Hu, Y., Mimura, N., Ohguchi, H., Cottini, F., Jakubikova, J., Munshi, N. C., Haggarty, S. J., Richardson, P. G., Hideshima, T., & Anderson, K. C.
Affiliations: Harvard University (US)
Massachusetts General Hospital (US)
Corresponding author: Anderson, K C
ORCID: Suzuki, R
Mazitschek, R
Ghosh, B
Cirstea, D
Hu, Y
Mimura, N
Ohguchi, H
Cottini, F
Munshi, N C
Haggarty, S J
Richardson, P G
Hideshima, T
Anderson, K C
Venue: Leukemia
Publisher: Springer Science and Business Media LLC
Published: 2013-08-05
Volume: 28
Issue: 3
Pages: 680-689
ISSN: 0887-6924 (ISSN-L)
1476-5551
DOI: 10.1038/leu.2013.231
PMC: PMC4165599
OpenAlex: W2004288940
Cited by: 159
References: 37
Citations by year: 2026: 5 · 2025: 10 · 2024: 11 · 2023: 15 · 2022: 15 · 2021: 10 · 2020: 15 · 2019: 13 · 2018: 14 · 2017: 16 · 2016: 6 · 2015: 18 · 2014: 8 · 2013: 3
FWCI: 5.38
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Leukemia (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (5p01ca078378-15, 5r01ca178264-05)
U.S. Public Health Service (P50100707)
National Institute on Drug Abuse (R01 DA02830)
National Cancer Institute (R01-CA178264, P01-CA-78378, P50CA086355, R01- CA50947, P01-CA078378, P50CA100707, R01CA050947, P01CA155258)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Keywords: HDAC3, multiple myeloma, HDAC3 inhibitors, STAT3 phosphorylation, STAT3 acetylation, bortezomib combination therapy, apoptosis, caspase activation, poly(ADP-ribose) polymerase, interleukin-6, mesenchymal stem cells, HDAC isoform selectivity, tumor growth inhibition
MeSH terms: Histone Deacetylase 3, Cell Division, Histone Deacetylases, Humans, Multiple Myeloma, Cell Line, Tumor, Gene Knockdown Techniques, Histone Deacetylase Inhibitors

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Histone deacetylase 3 as a novel therapeutic target in multiple myeloma

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