Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma
Open accessAbstract
Histone deacetylase (HDAC) enzymatic activity has been linked to the transcription of DNA in cancers including multiple myeloma (MM). Therefore, HDAC inhibitors used alone and in combination are being actively studied as novel therapies in MM. In the present study, we investigated the preclinical activity of ACY-1215, an HDAC6-selective inhibitor, alone and in combination with bortezomib in MM. Low doses of ACY-1215 combined with bortezomib triggered synergistic anti-MM activity, resulting in protracted endoplasmic reticulum stress and apoptosis via activation of caspase-3, caspase-8, and caspase-9 and poly (ADP) ribosome polymerase. In vivo, the anti-MM activity of ACY-1215 in combination with bortezomib was confirmed using 2 different xenograft SCID mouse models: human MM injected subcutaneously (the plasmacytoma model) and luciferase-expressing human MM injected intravenously (the disseminated MM model). Tumor growth was significantly delayed and overall survival was significantly prolonged in animals treated with the combination therapy. Pharmacokinetic data showed peak plasma levels of ACY-1215 at 4 hours after treatment coincident with an increase in acetylated α-tubulin, a marker of HDAC6 inhibition, by immunohistochemistry and Western blot analysis. These studies provide preclinical rationale for acetylated α-tubulin use as a pharmacodynamic biomarker in future clinical trials.
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ACY-1215 was reported as an inhibitor of multiple myeloma cell growth when combined with bortezomib.
“More recently, a new HDAC6 inhibitor ACY-1215 was reported as an inhibitor of multiple myeloma cell growth when combined with bortezomib (Santo et al, 2012).”
From A novel small molecule hydroxamate preferentially inhibits HDAC6 activity and tumour growth (2013) · cites this paper as Santo et al, 2012
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Cites
A Phase 2 Study of Bortezomib in Relapsed, Refractory Myeloma
Richardson, P. G., Barlogie, B., Berenson, J., Singhal, S., Jagannath, S., Irwin, D., Rajkumar, S. V., Srkalovic, G., Alsina, M., Alexanian, R., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa030288 · Cited by 2,632 · see citing works
Self-citationHaberland, M., Montgomery, R. L., & Olson, E. N. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2485 · Cited by 2,541 · see citing works
Functions of Site-Specific Histone Acetylation and Deacetylation
Shahbazian, M. D., & Grunstein, M. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.052705.162114 · Cited by 1,635 · see citing works
Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma
Kyle, R. A., & Rajkumar, S. V. (2008) · Leukemia · doi:10.1038/leu.2008.291 · Cited by 1,122 · see citing works
Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets
Hideshima, T., Mitsiades, C., Tonon, G., Richardson, P. G., & Anderson, K. C. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2189 · Cited by 932 · see citing works
Self-citationKelly, W. K., O’Connor, O. A., Krug, L. M., Chiao, J. H., Heaney, M. L., Curley, T., MacGregor‐Cortelli, B., Tong, W. P., Secrist, J. P., Schwartz, L. B., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.14.167 · Cited by 906 · see citing works
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 · see citing works
Self-citationMitsiades, C. S., Mitsiades, N., McMullan, C. J., Poulaki, V., Shringarpure, R., Akiyama, M., Hideshima, T., Chauhan, D., Joseph, M. G., Libermann, T. A., et al. (2004) · Cancer Cell · doi:10.1016/s1535-6108(04)00050-9 · Cited by 616 · see citing works
Self-citationHideshima, T., Bradner, J. E., Wong, J. Y. Y., Chauhan, D., Richardson, P. G. G., Schreiber, S. L., & Anderson, K. C. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503221102 · Cited by 598 · see citing works
Self-citationMitsiades, C. S., Mitsiades, N., McMullan, C. J., Poulaki, V., Shringarpure, R., Hideshima, T., Akiyama, M., Chauhan, D., Munshi, N. C., Gu, X., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2536759100 · Cited by 532 · see citing works
Self-citationMolecular mechanisms of novel therapeutic approaches for multiple myeloma
Hideshima, T., & Anderson, K. C. (2002) · Nature reviews. Cancer · doi:10.1038/nrc952 · Cited by 424 · see citing works
Self-citationHistone deacetylase inhibitors: Mechanisms of cell death and promise in combination cancer therapy
Carew, J. S., Giles, F. J., & Nawrocki, S. T. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.03.037 · Cited by 421 · see citing works
HDAC6, at the crossroads between cytoskeleton and cell signaling by acetylation and ubiquitination
Boyault, C., Sadoul, K., Pabion, M., & Khochbin, S. (2007) · Oncogene · doi:10.1038/sj.onc.1210614 · Cited by 397 · see citing works
Catley, L. P., Weisberg, E., Kiziltepe, T., Tai, Y., Hideshima, T., Neri, P., Tassone, P., Atadja, P. W., Chauhan, D., Munshi, N. C., et al. (2006) · Blood · doi:10.1182/blood-2006-04-016055 · Cited by 335 · see citing works
Self-citationMolecular sequelae of histone deacetylase inhibition in human malignant B cells
Mitsiades, N., Mitsiades, C. S., Richardson, P. G. G., McMullan, C. J., Poulaki, V., Fanourakis, G., Schlossman, R. L., Chauhan, D., Munshi, N. C., Hideshima, T., et al. (2003) · Blood · doi:10.1182/blood-2002-11-3514 · Cited by 294 · see citing works
Self-citationTargeting histone deacetylase in cancer therapy
Lin, S.-P., Chen, C., Lin, S.-P., Weng, J., & Chen, C. (2006) · Medicinal Research Reviews · doi:10.1002/med.20056 · Cited by 240 · see citing works
Nawrocki, S. T., Carew, J. S., Pino, M. S., Highshaw, R. A., Andtbacka, R. H. I., Dunner, K., Pal, A., Bornmann, W. G., Chiao, P. J., Huang, P., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2961 · Cited by 240 · see citing works
Davenport, E. L., Moore, H. E., Dunlop, A. S., Sharp, S. Y., Workman, P., Morgan, G. J., & Davies, F. E. (2007) · Blood · doi:10.1182/blood-2006-11-053728 · Cited by 238 · see citing works
Maiso, P., Carvajal‐Vergara, X., Ocio, E. M., López‐Pérez, R., Mateo, G., Gutierrez, N. C., Atadja, P. W., Pandiella, A., & Miguel, J. F. S. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4186 · Cited by 237 · see citing works
Badros, A. Z., Burger, A. M., Philip, S., Niesvizky, R., Kolla, S. S., Goloubeva, O. G., Harris, C., Zwiebel, J. A., Wright, J. J., Espinoza‐Delgado, I., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2850 · Cited by 231 · see citing works
Namdar, 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
Kozikowski, A. P., Tapadar, S., Luchini, D. N., Kim, K. H., & Billadeau, D. D. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm8002894 · Cited by 190 · see citing works
Santo, L., Vallet, S., Hideshima, T., Cirstea, D. D., Ikeda, H., Pozzi, S., Patel, K. J., Okawa, Y., Görgün, G., Perrone, G., et al. (2010) · Oncogene · doi:10.1038/onc.2009.510 · Cited by 144 · see citing works
Self-citationHistone deacetylases are critical targets of bortezomib-induced cytotoxicity in multiple myeloma
Kikuchi, J., Wada, T., Shimizu, R., Izumi, T., Akutsu, M., Mitsunaga, K., Noborio, K., Nobuyoshi, M., Ozawa, K., Kano, Y., et al. (2010) · Blood · doi:10.1182/blood-2009-07-235663 · Cited by 130 · see citing works
Histone deacetylases and epigenetic therapies of hematological malignancies
Mercurio, C., Minucci, S., & Pelicci, P. G. (2010) · Pharmacological Research · doi:10.1016/j.phrs.2010.02.010 · Cited by 125 · see citing works
Nawrocki, S. T., Carew, J. S., Maclean, K. H., Courage, J. F., Huang, P., Houghton, J. A., Cleveland, J. L., Giles, F. J., & McConkey, D. J. (2008) · Blood · doi:10.1182/blood-2007-12-130823 · Cited by 122 · see citing works
From the bench to the bedside: emerging new treatments in multiple myeloma
Mitsiades, C. S., Hayden, P. J., Anderson, K. C., & Richardson, P. G. G. (2007) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2007.09.008 · Cited by 74 · see citing works
Self-citationRaje, N. S., Hideshima, T., Mukherjee, S., Raab, M. S., Vallet, S., Chhetri, S., Cirstea, D. D., Pozzi, S., Mitsiades, C. S., Rooney, M., et al. (2009) · Leukemia · doi:10.1038/leu.2008.378 · Cited by 68 · see citing works
Self-citationSanto, L., Hideshima, T., Cirstea, D., Bandi, M., Nelson, E., Gorgun, G., Rodig, S., Vallet, S., Pozzi, S., Patel, K., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-3012 · Cited by 61 · see citing works
Self-citationEmerging Treatments for Multiple Myeloma: Beyond Immunomodulatory Drugs and Bortezomib
Mitsiades, C. S., Hideshima, T., Chauhan, D., McMillin, D. W., Klippel, S., Laubach, J. P., Munshi, N. C., Anderson, K. C., & Richardson, P. G. G. (2009) · Seminars in Hematology · doi:10.1053/j.seminhematol.2009.02.003 · Cited by 57 · see citing works
Self-citationJagannath, S., Dimopoulos, M. A., & Lonial, S. (2010) · Leukemia Research · doi:10.1016/j.leukres.2010.04.001 · Cited by 54 · see citing works
Lee, C., Wang, S., Huang, X., Ryder, J., & Liu, B. (2010) · Cancer Letters · doi:10.1016/j.canlet.2010.04.014 · Cited by 52 · see citing works
Vorinostat enhances the antimyeloma effects of melphalan and bortezomib
Campbell, R. A., Sanchez, E., Steinberg, J. A., Shalitin, D., Li, Z., Chen, H., & Berenson, J. R. (2009) · European Journal Of Haematology · doi:10.1111/j.1600-0609.2009.01384.x · Cited by 51 · see citing works
Rao, R., Nalluri, S., Fiskus, W. C., Savoie, A., Buckley, K. M., Ha, K., Balusu, R., Joshi, A., Coothankandaswamy, V., Tao, J., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-0529 · Cited by 50 · see citing works
Meister, S., Frey, B., Lang, V. R., Gaipl, U. S., Schett, G. A., Schlötzer-Schrehardt, U. M., & Voll, R. E. (2010) · Neoplasia · doi:10.1593/neo.10228 · Cited by 49 · see citing works
Sanchez, E., Shen, J., Steinberg, J. A., et al. (2010) · Leukemia Research · doi:10.1016/j.leukres.2010.06.026 · Cited by 44 · see citing works
Siegel, D. D., Sezer, O., Miguel, J. F. S., et al. (2008) · Blood · doi:10.1182/blood.v112.11.2781.2781 · Cited by 43 · see citing works
Weber, D. M., Jagannath, S., Mazumder, A., et al. (2007) · Blood · doi:10.1182/blood.v110.11.1172.1172 · Cited by 33 · see citing works
Harrison, S. J., Quach, H., Yuen, K., et al. (2008) · Blood · doi:10.1182/blood.v112.11.3698.3698 · Cited by 33 · see citing works
Tong, W.-G., Wei, Y., Stevenson, W. S., et al. (2009) · Leukemia Research · doi:10.1016/j.leukres.2009.07.024 · Cited by 28 · see citing works
Proteasome and HDAC: who's zooming who?
McConkey, D. J. (2010) · Blood · doi:10.1182/blood-2010-04-278507 · Cited by 25 · see citing works
Miguel, J. F. S., Sezer, O., Siegel, D. S. D., et al. (2009) · Blood · doi:10.1182/blood.v114.22.3852.3852 · Cited by 15 · see citing works
Weber, D. M., Jagannath, S., Sobecks, R. M., et al. (2008) · Blood · doi:10.1182/blood.v112.11.3711.3711 · Cited by 11 · see citing works
Miguel, J. F. S., Sezer, Ö., Siegel, D. S., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.15_suppl.8001 · Cited by 10 · see citing works
Roervig, S., Honoré, C., Larsson, L., et al. (2008) · Blood · doi:10.1182/blood.v112.11.1267.1267 · Cited by 5 · see citing works
Kimura, A., Rieger, M. A., Chen, W., et al. (2008) · Blood · doi:10.1182/blood.v112.11.1272.1272 · Cited by 2 · see citing works
Mohamed-Hadley, A. A., Liebermann, D. A., & Hoffman, B. (2009) · Blood · doi:10.1182/blood.v114.22.1481.1481 · Cited by 1 · see citing works
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Self-citationHistone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders
Falkenberg, K. J., & Johnstone, R. W. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4360 · Cited by 1,564 · see citing works
New 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
HDAC Inhibition Upregulates PD-1 Ligands in Melanoma and Augments Immunotherapy with PD-1 Blockade
Woods, D. M., Sodré, A. L., Villagra, A., Sarnaik, A., Sotomayor, E. M., & Weber, J. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0077-t · Cited by 454 · see citing works
Structural insights into HDAC6 tubulin deacetylation and its selective inhibition
Miyake, Y., Keusch, J. J., Wang, L., Saito, M., Hess, D., Wang, X., Melancon, B. J., Helquist, P., Gut, H., & Matthias, P. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2140 · Cited by 315 · see citing works
Targeting histone deacetylases for cancer therapy: Trends and challenges
Liang, T., Wang, F., Elhassan, R. M., Cheng, Y., Tang, X., Chen, W., Fang, H., & Hou, X. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.02.007 · Cited by 222 · see citing works
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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
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Wu, H., Yang, K., Zhang, Z., Leisten, E. D., Li, Z., Xie, H., Liu, J., Smith, K. A., Novakova, Z., Barinka, C., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00516 · Cited by 180 · see citing works
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Recent advances in the discovery of potent and selective HDAC6 inhibitors
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- Authors
- 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., Cirstea, D., Rodig, S., Eda, H., Scullen, T., Canavese, M., Bradner, J., Anderson, K. C., Jones, S. S., & Raje, N.
- Affiliations
- Massachusetts General Hospital (US)
- Harvard University (US)
- Acetylon Pharmaceuticals (United States) (US)
- Acetylon Pharmaceuticals, Boston, MA,
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2012-03-15
- Volume
- 119
- Issue
- 11
- Pages
- 2579-2589
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC3337713
- OpenAlex
- W2095026025
- Cited by
- 616
- References
- 47
- Citations by year
- 2026: 15 · 2025: 25 · 2024: 20 · 2023: 38 · 2022: 40 · 2021: 56 · 2020: 42 · 2019: 61 · 2018: 53 · 2017: 53 · 2016: 47 · 2015: 52 · 2014: 51 · 2013: 41 · 2012: 21
- FWCI
- 35.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (K08CA128972, P50CA100707, R01CA050947)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Keywords
- ACY-1215, HDAC6 inhibitors, bortezomib, multiple myeloma, combination therapy, synergistic antitumor effect, endoplasmic reticulum stress, apoptosis, caspase activation, PARP activation, acetylated alpha-tubulin, pharmacodynamic biomarkers, pharmacokinetics, xenograft mouse model, plasmacytoma
- MeSH terms
- Bortezomib, Histone Deacetylase 6, Animals, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Boronic Acids, Drug Synergism, Fluorescent Antibody Technique, Histone Deacetylases, Humans, Hydroxamic Acids, Immunoenzyme Techniques, Male, Plasmacytoma, Pyrazines, Pyrimidines, RNA, Messenger, Tissue Distribution, Tumor Cells, Cultured, Blotting, Western, Mice, SCID, Apoptosis, Xenograft Model Antitumor Assays, Cell Proliferation, Mice, Histone Deacetylase Inhibitors, Endoplasmic Reticulum Stress, Real-Time Polymerase Chain Reaction
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