Development of HDAC Inhibitors Exhibiting Therapeutic Potential in T-Cell Prolymphocytic Leukemia

Toutah, Krimo; Nawar, Nabanita; Timonen, Sanna; Sorger, Helena; Raouf, Yasir S.; Bukhari, Shazreh; von Jan, Jana; Ianevski, Aleksandr; Gawel, Justyna M.; Olaoye, Olasunkanmi O.; Geletu, Mulu; Abdeldayem, Ayah; Israelian, Johan; Radu, Tudor B.; Sedighi, Abootaleb; Bhatti, Muzaffar N.; Hassan, Muhammad Murtaza; Manaswiyoungkul, Pimyupa; Shouksmith, Andrew E.; Neubauer, Heidi A.; de Araujo, Elvin D.; Aittokallio, Tero; Krämer, Oliver H.; Moriggl, Richard; Mustjoki, Satu; Herling, Marco; Gunning, Patrick T.

doi:10.1021/acs.jmedchem.1c00420

Cited by 56Histone Deacetylase Inhibitors ResearchChronic Lymphocytic Leukemia ResearchProtein Degradation and Inhibitors

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Development of HDAC Inhibitors Exhibiting Therapeutic Potential in T-Cell Prolymphocytic Leukemia

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Toutah, Krimo, Nawar, Nabanita, Timonen, Sanna, Sorger, Helena, Raouf, Yasir S., Bukhari, Shazreh, von Jan, Jana, Ianevski, Aleksandr, Gawel, Justyna M., Olaoye, Olasunkanmi O., Geletu, Mulu, Abdeldayem, Ayah, Israelian, Johan, Radu, Tudor B., Sedighi, Abootaleb, Bhatti, Muzaffar N., Hassan, Muhammad Murtaza, Manaswiyoungkul, Pimyupa, Shouksmith, Andrew E., Neubauer, Heidi A., de Araujo, Elvin D., Aittokallio, Tero, Krämer, Oliver H., Moriggl, Richard, Mustjoki, Satu, Herling, Marco, Gunning, Patrick T.·2021·Journal of Medicinal Chemistry

DOI 10.1021/acs.jmedchem.1c00420PMC PMC8237267

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Abstract

Epigenetic targeting has emerged as an efficacious therapy for hematological cancers.The rare and incurable T-cell prolymphocytic leukemia (T-PLL) is known for its aggressive clinical course.Current epigenetic agents such as histone deacetylase (HDAC) inhibitors are increasingly used for targeted therapy.Through a structure-activity relationship (SAR) study, we developed an HDAC6 inhibitor KT-531, which exhibited higher potency in T-PLL compared to other hematological cancers.KT-531 displayed strong HDAC6 inhibitory potency and selectivity, on-target biological activity, and a safe therapeutic window in nontransformed cell lines.In primary T-PLL patient cells, where HDAC6 was found to be overexpressed, KT-531 exhibited strong biological responses, and safety in healthy donor samples.Notably, combination studies in T-PLL patient samples demonstrated KT-531 synergizes with approved cancer drugs, bendamustine, idasanutlin, and venetoclax.Our work suggests HDAC inhibition in T-PLL could afford sufficient therapeutic windows to achieve durable remission either as standalone or in combination with targeted drugs.

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Installing a hydroxamate on any molecule with limited optimization is strongly biased for generating pan-HDACi, among other possible interactions with metalloproteins.
“Despite their exquisite potency against HDACs, installing a hydroxamate on any molecule with limited optimization is strongly biased for generating pan-HDACi, among many other possible interactions with metalloproteins (aminopeptidases, carbonic anhydrase, etc.) that can be chelated in a similar manner [38].”
From Medicinal chemistry advances in targeting class I histone deacetylases (2023) · cites this paper as [38]
The Introduction (page not provided) says that HDAC inhibitors generally exhibit broad-spectrum activity, and the Results show that changes to a hydroxamic-acid-containing compound alter its HDAC selectivity. The paper does not establish that adding a hydroxamate to any molecule with limited optimization tends to produce a pan-HDAC inhibitor, or that such compounds interact with aminopeptidases, carbonic anhydrase, or other metalloproteins. (LLM, conf=0.80)
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Friesner, R. A., Banks, J. L., Murphy, R. B., Halgren, T. A., Klicic, J. J., Mainz, D. T., Repasky, M. P., Knoll, E. H., Shelley, M., Perry, J. K., et al. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm0306430 · Cited by 10,057
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Friesner, R. A., Murphy, R. B., Repasky, M. P., Frye, L. L., Greenwood, J. R., Halgren, T. A., Sanschagrin, P. C., & Mainz, D. T. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm051256o · Cited by 7,012
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Halgren, T. A., Murphy, R. B., Friesner, R. A., Beard, H. S., Frye, L. L., Pollard, W. T., & Banks, J. L. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm030644s · Cited by 5,340
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Rhodes, D. R., Yu, J., Sundaram, S. K., Deshpande, N., Varambally, R., Ghosh, D., Barrette, T. R., Pander, A., & Chinnaiyan, A. M. (2004) · Neoplasia · doi:10.1016/s1476-5586(04)80047-2 · Cited by 3,590
ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets
Souers, A. J., Leverson, J. D., Boghaert, E. R., Ackler, S. L., Catron, N. D., Chen, J., Dayton, B. D., Ding, H., Enschede, S. H., Fairbrother, W. J., et al. (2013) · Nature Medicine · doi:10.1038/nm.3048 · Cited by 3,058
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Allfrey, V. G., Faulkner, R. D., & Mirsky, A. E. (1964) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.51.5.786 · Cited by 2,788
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Haberland, M., Montgomery, R. L., & Olson, E. N. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2485 · Cited by 2,600
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Feinberg, A. P., & Tycko, B. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1279 · Cited by 2,404
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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
Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia
Roberts, A. W., Davids, M. S., Pagel, J. M., Kahl, B. S., Puvvada, S. D., Gerecitano, J. F., Kipps, T. J., Anderson, M. A., Brown, J. R., Gressick, L. A., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1513257 · Cited by 1,930
Histone Deacetylase Inhibitors as Anticancer Drugs
Eckschlager, T., Plch, J., Stiborova, M., & Hrabeta, J. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18071414 · Cited by 1,206
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
Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease
Hockly, E., Richon, V. M., Woodman, B., Smith, D. L., Zhou, X., Rosa, E., Sathasivam, K., Ghazi‐Noori, S., Mahal, A., Lowden, P. A. S., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0437870100 · Cited by 847
HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo
Zhang, Y., Li, N., Caron, C., Matthias, G., Hess, D., Khochbin, S., & Matthias, P. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg115 · Cited by 740 · cited 1×
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Thiagalingam, S., Cheng, K., Lee, H. J., Mineva, N. D., Thiagalingam, A., & Ponte, J. F. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb05964.x · Cited by 700
Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma
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., et al. (2012) · Blood · doi:10.1182/blood-2011-10-387365 · Cited by 616
Mice Lacking Histone Deacetylase 6 Have Hyperacetylated Tubulin but Are Viable and Develop Normally
Zhang, Y., Kwon, S., Yamaguchi, T., Cubizolles, F., Rousseaux, S., Kneissel, M., Cao, C., Li, N., Cheng, H.-L., Chua, K., et al. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01154-06 · Cited by 559
The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species
Ruefli, A. A., Ausserlechner, M. J., Bernhard, D., Sutton, V. R., Tainton, K. M., Kofler, R., Smyth, M. J., & Johnstone, R. W. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.191208598 · Cited by 492
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Lund, A. H., & van Lohuizen, M. (2004) · Genes & Development · doi:10.1101/gad.1232504 · Cited by 489
A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas
Balasubramanian, S., Ramos, J., Luo, W., Sirisawad, M., Verner, E., & Buggy, J. J. (2008) · Leukemia · doi:10.1038/leu.2008.9 · Cited by 458
FDA Approval: Belinostat for the Treatment of Patients with Relapsed or Refractory Peripheral T-cell Lymphoma
Lee, H.-Z., Kwitkowski, V. E., Valle, P. L. D., Ricci, M., Saber, H., Habtemariam, B. A., Bullock, J. M., Bloomquist, E. W., Shen, Y. L., Chen, X.-H., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-3119 · Cited by 365
Quantitative scoring of differential drug sensitivity for individually optimized anticancer therapies
Yadav, B., Pemovska, T., Szwajda, A., Kulesskiy, E., Kontro, M., Karjalainen, R., Majumder, M. M., Malani, D., Murumägi, A., Knowles, J., et al. (2014) · Scientific Reports · doi:10.1038/srep05193 · Cited by 358
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Ellis, L., Pan, Y., Smyth, G. K., George, D. J., McCormack, C. J., Williams-Truax, R., Mita, M. M., Beck, J., Burris, H. A., Ryan, G. F., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-4262 · Cited by 296
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Grant, C. M., Rahman, F., Piekarz, R., Peer, C. J., Frye, R., Robey, R. W., Gardner, E. R., Figg, W. D., & Bates, S. E. (2010) · Expert Review of Anticancer Therapy · doi:10.1586/era.10.88 · Cited by 295
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Lombardi, P. M., Cole, K., Dowling, D., & Christianson, D. W. (2011) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2011.08.004 · Cited by 287
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Tran, A. D.-A., Marmo, T. P., Salam, A. A., Che, S., Finkelstein, E., Kabarriti, R., Xenias, H. S., Mazitschek, R., Hubbert, C., Kawaguchi, Y., et al. (2007) · Journal of Cell Science · doi:10.1242/jcs.03431 · Cited by 281
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Kiel, M. J., Velusamy, T., Rolland, D. C. M., Sahasrabuddhe, A. A., Chung, F., Bailey, N. G., Schrader, A., Li, B., Li, J. Z., Ozel, A. B., et al. (2014) · Blood · doi:10.1182/blood-2014-03-559542 · Cited by 256
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Self-citation
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Tang, J., Yan, H., & Zhuang, S. (2013) · Clinical Science · doi:10.1042/cs20120504 · Cited by 204
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Bergman, J. A., Woan, K. V., Perez-Villarroel, P., Villagra, A., Sotomayor, E. M., & Kozikowski, A. P. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm301098e · Cited by 200
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Dearden, C. E. (2012) · Blood · doi:10.1182/blood-2012-01-380139 · Cited by 192
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Kumagai, T., Wakimoto, N., Yin, D., Gery, S., Kawamata, N., Takai, N., Komatsu, N., Чумаков, А. Е., Imai, Y., & Koeffler, H. P. (2007) · International Journal of Cancer · doi:10.1002/ijc.22558 · Cited by 183
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Heider, U., Rademacher, J., Lamottke, B., Mieth, M., Möbs, M., von Metzler, I., Assaf, C., & Sezer, O. (2009) · European Journal Of Haematology · doi:10.1111/j.1600-0609.2009.01239.x · Cited by 173
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Staber, P. B., Herling, M., Bellido, M., Jacobsen, E. D., Davids, M. S., Kadia, T. M., Shustov, A. R., Tournilhac, O., Bachy, E., Zaja, F. F., et al. (2019) · Blood · doi:10.1182/blood.2019000402 · Cited by 164
Self-citation
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Herling, M., Patel, K. A., Teitell, M. A., Konopleva, M. Y., Ravandi, F., Kobayashi, R., & Jones, D. M. (2007) · Blood · doi:10.1182/blood-2007-07-101519 · Cited by 140
Self-citation
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Huang, P., Almeciga-Pinto, I., Jarpe, M. B., van Duzer, J. H., Mazitschek, R., Yang, M., Jones, S. S., & Quayle, S. N. (2016) · Oncotarget · doi:10.18632/oncotarget.13738 · Cited by 138
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Self-citation
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Schrader, A., Crispatzu, G., Oberbeck, S., Mayer, P., Pützer, S., von Jan, J., Vasyutina, E. L., Warner, K., Weit, N., Pflug, N., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02688-6 · Cited by 105
Self-citation
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Yan, W., Herman, J. G., & Guo, M. (2015) · Epigenomics · doi:10.2217/epi.15.84 · Cited by 98
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Heider, U., von Metzler, I., Kaiser, M., Rosche, M., Sterz, J., Rötzer, S., Rademacher, J., Jakob, C., Fleissner, C., Kuckelkorn, U., et al. (2007) · European Journal Of Haematology · doi:10.1111/j.1600-0609.2007.00995.x · Cited by 97
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Andersson, E. I., Pützer, S., Yadav, B., Dufva, O., Khan, S., He, L., Sellner, L., Schrader, A., Crispatzu, G., Oleś, M., et al. (2017) · Leukemia · doi:10.1038/leu.2017.252 · Cited by 94
Self-citation
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Cosenza, M., & Pozzi, S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082337 · Cited by 84
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Pandolfi, P. P. (2001) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s002800100322 · Cited by 82
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Self-citation
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Stengel, A., Kern, W., Zenger, M., Perglerová, K., Schnittger, S., Haferlach, T., & Haferlach, C. (2015) · Genes Chromosomes and Cancer · doi:10.1002/gcc.22313 · Cited by 79
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He, L., Tang, J. P., Andersson, E. I., Timonen, S., Koschmieder, S., Wennerberg, K., Mustjoki, S. M., & Aittokallio, T. A. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-3644 · Cited by 77
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Self-citation
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Self-citation
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Hassan, M. M., Israelian, J., Nawar, N., Ganda, G., Manaswiyoungkul, P., Raouf, Y. S., Armstrong, D. R., Sedighi, A., Olaoye, O. O., Erdogan, F., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01025 · Cited by 51
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North, B. J., Almeciga-Pinto, I., Tamang, D., Yang, M., Jones, S. S., & Quayle, S. N. (2017) · PLoS ONE · doi:10.1371/journal.pone.0173507 · Cited by 49
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Synergistic antitumor effects of the combined treatment with an HDAC6 inhibitor and a COX-2 inhibitor through activation of PTEN
Zhang, G., & Gan, Y. (2017) · Oncology Reports · doi:10.3892/or.2017.5981 · Cited by 24
Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas
Orlova, A., Wingelhofer, B., Neubauer, H. A., Maurer, B., Berger‐Becvar, A., Keserű, G. M., Gunning, P. T., Valent, P., & Moriggl, R. (2017) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2018.1406924 · Cited by 22
Self-citation
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Self-citation
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Self-citation
Models for mature T-cell lymphomas—A critical appraisal of experimental systems and their contribution to current T-cell tumorigenic concepts
Warner, K., Crispatzu, G., Al-Ghaili, N., Weit, N., Florou, V., You, M. J., Newrzela, S., & Herling, M. (2013) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2013.07.014 · Cited by 17
Self-citation
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Self-citation

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10.1038/leu.2017.252 · DOI
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Medicinal chemistry updates of novel HDACs inhibitors (2020 to present)
He, X., Hui, Z., Xu, L., Bai, R., Gao, Y., Wang, Z., Xie, T., & Ye, X.-Y. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113946 · Cited by 89
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Nawar, N., Bukhari, S., Adile, A., Suk, Y., Manaswiyoungkul, P., Toutah, K., Olaoye, O. O., Raouf, Y. S., Sedighi, A., Garcha, H. K., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01585 · Cited by 38
Self-citation
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Zeyen, P., Zeyn, Y., Herp, D., Mahmoudi, F., Yesiloglu, T. Z., Erdmann, F., Schmidt, M., Robaa, D., Romier, C., Ridinger, J., et al. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114272 · Cited by 36
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Ru, J., Wang, Y., Li, Z., Wang, J., Ren, C., & Zhang, J. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115800 · Cited by 27
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Gutierrez, M. G., Bladek, P., Goksu, B. N. B., Murga‐Zamalloa, C., Bixby, D. L., & Wilcox, R. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512106 · Cited by 25
Next-Generation HDAC Inhibitors: Advancing Zinc-Binding Group Design for Enhanced Cancer Therapy
Hawash, M. (2025) · Cells · doi:10.3390/cells14241997 · Cited by 21
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Mukherjee, A., Zamani, F., & Suzuki, T. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c01160 · Cited by 21
Advanced Pathogenetic Concepts in T-Cell Prolymphocytic Leukemia and Their Translational Impact
Braun, T., Dechow, A., Friedrich, G., Seifert, M., Stachelscheid, J., & Herling, M. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.775363 · Cited by 21
Self-citation
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Li, Z., Zhao, C. H., He, G., Wang, Y., Wang, Y., & Ma, X. (2022) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2022.117028 · Cited by 20
Slow-Binding and Covalent HDAC Inhibition: A New Paradigm?
Raouf, Y. S., & Moreno–Yruela, C. (2024) · JACS Au · doi:10.1021/jacsau.4c00828 · Cited by 18
Self-citation
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
“Hence, hydroxamates are often faced with selectivity barriers, which are mitigated via optimization of the linker and cap groups [39].”
BackgroundSelf-citation
Discovery of a Dual‐Target Inhibitor of CDK7 and HDAC1 That Induces Apoptosis and Inhibits Migration in Colorectal Cancer**
Chen, Y., Zhang, S., Li, Z., Yin, B., Liu, Y., & Zhang, L. (2023) · ChemMedChem · doi:10.1002/cmdc.202300281 · Cited by 17
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Raouf, Y. S., Sedighi, A., Geletu, M., Frere, G. A., Allan, R. G., Nawar, N., de Araujo, E. D., & Gunning, P. T. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c01236 · Cited by 17
Self-citation
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Self-citation
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Self-citation
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Xu, X. J., Zhang, D., Zhao, T., Wang, M., Li, Y., Du, Q., Kou, J., Li, Z., & Bian, J. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114228 · Cited by 8
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High Efficacy and Drug Synergy of HDAC6-Selective Inhibitor NN-429 in Natural Killer (NK)/T-Cell Lymphoma
Garcha, H. K., Nawar, N., Sorger, H., Erdogan, F., Aung, M. M. K., Sedighi, A., Manaswiyoungkul, P., Seo, H., Schönefeldt, S., Pölöske, D., et al. (2022) · Pharmaceuticals · doi:10.3390/ph15111321 · Cited by 5
Self-citation
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Baselious, F., Hilscher, S., Handke, L., Bařinka, C., Schutkowski, M., & Sippl, W. (2025) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2025.110695 · Cited by 2
Recent review on selective histone deacetylase inhibitors in cancer therapy
El-hameed, A. I. A., Mohamed, M. F. A., & Beshr, E. A. M. (2023) · Octahedron Drug Research · doi:10.21608/odr.2023.244352.1033 · Cited by 1
Fluorescence Polarization-Based Competition Assays to Evaluate Histone Deacetylase 6 Inhibitors
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Self-citation
Prolymphocytic Leukaemia: an Update on Biology and Treatment
El‐Sharkawi, D., & Dearden, C. E. (2024) · Current Oncology Reports · doi:10.1007/s11912-023-01485-3 · Cited by 1
Proteasome Inhibitors Induce Apoptosis in Ex Vivo Cells of T-Cell Prolymphocytic Leukemia
Gasparini, V. R., Rampazzo, E., Barilà, G., Buratin, A., Buson, E., Calabretto, G., Vicenzetto, C., Orsi, S., Tonini, A., Teramo, A., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252413573 · Cited by 1
Design, synthesis, and biological evaluation of estratriene-based hydroxamic acid derivatives as histone deacetylase inhibitors
Chen, H., Li, Y., Liang, Z., Zhong, Z., Huang, Y., Liu, Z., Gu, Y., Jiang, L., Gan, C., & Gan, C. (2025) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2025.106867 · Cited by 1
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Self-citation
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Clinical analysis of prolymphoblastic leukemia: the rare hematological malignancy in the elderly.
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Structure similarity based screening coupled to integrated structural biochemistry approach for exploring the high affinity inhibitors against histone deacetylase (HDAC)-6
Ganai, S. A., & Suma Mohan, S. (2025) · In Silico Pharmacology · doi:10.1007/s40203-024-00294-1
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Li, Y., Liang, Z., Zhong, Z., Wei, Y., Liu, Q., Zhan, J., & Gan, C. (2025) · Chinese Journal of Organic Chemistry · doi:10.6023/cjoc202412017
Metabolism-driven epigenetics in high-risk T-cell acute lymphoblastic leukemia
Guo, S. (2024) · theses.fr (ABES) · doi:10.70675/d7a710b1zec35z4c09zb08ezd28084851c9f
Modular Rh‐Catalyzed Synthesis and Biological Profiling of Diverse Pentafluorobenzenesulfonamide Reactive Fragments
Chesti, J., Miles, J. A., Wade, G. J., Grossman, S., Preston, G. W., Bayliss, R. W., Warriner, S. L., Wright, M. H., & Nelson, A. S. (2026) · Chemistry - A European Journal · doi:10.1002/chem.202600009
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Chen, H., Zhou, S., Ji, F., Chen, K., Jian, L., Wang, Y., Yao, H., Yang, M., & Wu, H. (2026) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-026-09133-x
BindingDB Entry 50021326: Development of a tetrahydroindazolone-based HDAC6 inhibitor with in-vivo anti-arthritic activity.
BindingDB (2025) · UC San Diego · doi:10.7270/q2kk9hf6
BindingDB Entry 50022172: Hydroxamic acid hybrids: Histone deacetylase inhibitors with anticancer therapeutic potency.
BindingDB (2025) · UC San Diego · doi:10.7270/q2j38z98
BindingDB Entry 50017631: Discovery of HDAC6-Selective Inhibitor NN-390 with
BindingDB (2023) · UC San Diego · doi:10.7270/q2qv3rkm
BindingDB Entry 50020572: Discovery of YSR734: A Covalent HDAC Inhibitor with Cellular Activity in Acute Myeloid Leukemia and Duchenne Muscular Dystrophy.
BindingDB (2024) · UC San Diego · doi:10.7270/q2bz6bhh
BindingDB Entry 50017154: Novel biphenyl-based scaffold as potent and selective histone deacetylase 6 (HDAC6) inhibitors: Identification, development and pharmacological evaluation.
BindingDB (2023) · UC San Diego · doi:10.7270/q2zk5mqx
BindingDB Entry 50019897: Discovery of Novel 1,2,3,4-Tetrahydrobenzofuro[2,3-
BindingDB (2024) · UC San Diego · doi:10.7270/q2h41wtj
BindingDB Entry 50016856: Medicinal chemistry updates of novel HDACs inhibitors (2020 to present).
BindingDB (2023) · UC San Diego · doi:10.7270/q2348qfg
BindingDB Entry 50019324: Evolution of Slow-Binding Inhibitors Targeting Histone Deacetylase Isoforms.
BindingDB (2024) · UC San Diego · doi:10.7270/q2p55sv5
BindingDB Entry 50021668: Technologies of targeting histone deacetylase in drug discovery: Current progress and emerging prospects.
BindingDB (2025) · UC San Diego · doi:10.7270/q2vq37b4
BindingDB Entry 50018029: Identification of PI3K/HDAC Dual-targeted inhibitors with subtype selectivity as potential therapeutic agents against solid Tumors: Building HDAC6 potency in a Quinazolinone-based PI3Kδ-selective template.
BindingDB (2023) · UC San Diego · doi:10.7270/q20869dr

Optimizing drug combinations for T-PLL: restoring DNA damage and P53-mediated apoptotic responses
von Jan, J., Timonen, S., Braun, T., Jiang, Q., Ianevski, A., Peng, Y., McConnell, K. K., Sindaco, P., Müller, T. A., Pützer, S., et al. (2024) · Blood · doi:10.1182/blood.2023022884 · Cited by 13
Self-citation
[Research Advances of Genetics, Diagnosis and Treatment of T-cell Prolymphocytic Leukemia--Review].
Lai, M.-F., & Li, F. (2021) · PubMed · doi:10.19746/j.cnki.issn.1009-2137.2021.06.050
Management of T‐cell malignancies: Bench‐to‐bedside targeting of epigenetic biology
Sabzevari, A., Ung, J., Craig, J. W., Jayappa, K. D., Pal, I., Feith, D. J., Loughran, T. P., & O’Connor, O. A. (2025) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.70001 · Cited by 4
Epigenetic therapy overcomes treatment resistance in T cell prolymphocytic leukemia
Hasanali, Z. S., Saroya, B. S., Stuart, A., Shimko, S., Evans, J. J., Shah, M. V., Sharma, K., Leshchenko, V. V., Parekh, S. S., Loughran, T. P., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa5079 · Cited by 53
Therapeutic Potential of Selected HDAC Targeting in Mature T-cell Neoplasms
Peng, Y. (2025) · Qucosa (Saxon State and University Library Dresden)

Authors: Toutah, K., Nawar, N., Timonen, S., Sorger, H., Raouf, Y. S., Bukhari, S., von Jan, J., Ianevski, A., Gawel, J. M., Olaoye, O. O., Geletu, M., Abdeldayem, A., Israelian, J., Radu, T. B., Sedighi, A., Bhatti, M. N., Hassan, M. M., Manaswiyoungkul, P., Shouksmith, A. E., Neubauer, H. A., de Araujo, E. D., Aittokallio, T., Krämer, O. H., Moriggl, R., Mustjoki, S., Herling, M., & Gunning, P. T.
Affiliations: University of Toronto (CA)
University of Helsinki (FI)
University of Veterinary Medicine Vienna (AT)
University of Cologne (DE)
Oslo University Hospital (NO)
University Medical Center of the Johannes Gutenberg University Mainz (DE)
Corresponding author: Moriggl, Richard
Mustjoki, Satu
Herling, Marco
Gunning, Patrick T.
ORCID: Timonen, Sanna
Sorger, Helena
Raouf, Yasir S.
Ianevski, Aleksandr
Gawel, Justyna M.
Olaoye, Olasunkanmi O.
Abdeldayem, Ayah
Israelian, Johan
Sedighi, Abootaleb
Hassan, Muhammad Murtaza
Manaswiyoungkul, Pimyupa
Neubauer, Heidi A.
de Araujo, Elvin D.
Aittokallio, Tero
Krämer, Oliver H.
Moriggl, Richard
Mustjoki, Satu
Herling, Marco
Gunning, Patrick T.
Venue: Journal of Medicinal Chemistry
Publisher: American Chemical Society (ACS)
Published: 2021-06-08
Volume: 64
Issue: 12
Pages: 8486-8509
ISSN: 0022-2623 (ISSN-L)
1520-4804
DOI: 10.1021/acs.jmedchem.1c00420
PMC: PMC8237267
OpenAlex: W3171699140
Cited by: 51
References: 71
Citations by year: 2026: 3 · 2025: 12 · 2024: 7 · 2023: 11 · 2022: 16 · 2021: 2
FWCI: 3.14
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: Journal of Medicinal Chemistry (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
Työväentutkimus Vuosikirja (submittedVersion)
NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
Funders: Sy??p??j??rjest??t
Canada Research Chairs (950-232042)
Sy??p??s????ti??
Leukemia and Lymphoma Society of Canada
Canadian Institutes of Health Research (MOP-130424, MOP-137036)
Austrian Science Fund (SFB-F04707, SFB-F06105)
Academy of Finland (310507, 313267, 326238)
Horizon 2020 Framework Programme
Natural Sciences and Engineering Research Council of Canada (RGPIN-2014-05767)
H2020 European Research Council
Canadian Cancer Society Research Institute (703963)
Canadian Breast Cancer Foundation (705456)
Ontario Ministry of Research, Innovation and Science (34876)
Liechtenstein
Sigrid Juselius Foundation
Helse S??r-??st
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
Keywords: histone deacetylase inhibitors, T-cell prolymphocytic leukemia, histone deacetylase, bendamustine, idasanutlin, venetoclax, drug synergy, combination therapy, sustained remission
MeSH terms: Bendamustine Hydrochloride, Histone Deacetylase 6, Animals, Antineoplastic Agents, Drug Synergism, Humans, Hydroxamic Acids, Male, Pyrrolidines, Structure-Activity Relationship, Sulfonamides, Molecular Structure, Leukemia, Prolymphocytic, T-Cell, Apoptosis, Bridged Bicyclo Compounds, Heterocyclic, Cell Line, Tumor, Mice, Histone Deacetylase Inhibitors, Molecular Docking Simulation, para-Aminobenzoates

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Development of HDAC Inhibitors Exhibiting Therapeutic Potential in T-Cell Prolymphocytic Leukemia

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