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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Review Article

Multi-targeted HDAC Inhibitors as Anticancer Agents: Current Status and Future Prospective

Author(s): Vijay K. Patel, Ekta Shirbhate, Priya Tiwari, Rakesh Kore, Ravichandran Veerasamy, Achal Mishra and Harish Rajak*

Volume 30, Issue 24, 2023

Published on: 04 November, 2022

Page: [2762 - 2795] Pages: 34

DOI: 10.2174/0929867329666220922105615

Price: $65

Abstract

Multi-targeted agents can interact with multiple targets sequentially, resulting in synergistic and more effective therapies for several complicated disorders, including cancer, even with relatively modest activity. Histone deacetylase (HDAC) inhibitors are low molecular weight small compounds that increase the acetylation of histone and nonhistone proteins, altering gene expression and thereby impacting angiogenesis, metastasis, and apoptosis, among other processes. The HDAC inhibitors affect multiple cellular pathways thus producing adverse issues, causing therapeutic resistance, and they have poor pharmacokinetic properties. The designing of HDAC-based dual/multi-target inhibitor is an important strategy to overcome adverse effects, drug resistance and increase the effectiveness in controlling cancer. The selection of target combinations to design multitarget HDAC inhibitor is generally accomplished on the basis of systematic highthroughput screening (HTS), network pharmacology analysis methods. The identification of the pharmacophore against individual targets is performed using rational or computation methods. The identified pharmacophore can combine with merged, fused, or linked with the cleavable or non-cleavable linker to retain the interaction with the original target while being compatible with the other target. The objective of this review is to elucidate the potential targets' design strategies, biological activity, and the recent development of dual/multi-targeting HDAC inhibitors as potential anticancer agents. This review elucidates the designing strategies of the potential target along with biological activity and the recent development of dual/multi-targeting HDAC inhibitors as potential anticancer agents. The development of HDAC-based dual/multi-target inhibitors is important for overcoming side effects, drug resistance, and effective cancer control.

Keywords: Histone deacetylase, HDAC inhibitor, Anticancer, Dual/multi-targeting, Designing strategies, Computational methods, Recent development.

« Previous Next »
[1]
Li, X.; Li, X.; Liu, F.; Li, S.; Shi, D. Rational multitargeted drug design strategy from the perspective of a medicinal chemist. J. Med. Chem., 2021, 64(15), 10581-10605.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00683] [PMID: 34313432]
[2]
Zhang, W.; Pei, J.; Lai, L. Computational multitarget drug design. J. Chem. Inf. Model., 2017, 57(3), 403-412.
[http://dx.doi.org/10.1021/acs.jcim.6b00491] [PMID: 28166637]
[3]
Proschak, E.; Stark, H.; Merk, D. Polypharmacology by design: A medicinal chemist’s perspective on multitargeting compounds. J. Med. Chem., 2019, 62(2), 420-444.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00760] [PMID: 30035545]
[4]
Shang, E.; Yuan, Y.; Chen, X.; Liu, Y.; Pei, J.; Lai, L. De novo design of multitarget ligands with an iterative fragment-growing strategy. J. Chem. Inf. Model., 2014, 54(4), 1235-1241.
[http://dx.doi.org/10.1021/ci500021v] [PMID: 24611712]
[5]
Papavassiliou, K.A.; Papavassiliou, A.G. Histone deacetylases inhibitors: Conjugation to other anti-tumour pharmacophores provides novel tools for cancer treatment. Expert Opin. Investig. Drugs, 2014, 23(3), 291-294.
[http://dx.doi.org/10.1517/13543784.2014.857401] [PMID: 24205827]
[6]
Ramsay, R.R.; Popovic-Nikolic, M.R.; Nikolic, K.; Uliassi, E.; Bolognesi, M.L. A perspective on multi‐target drug discovery and design for complex diseases. Clin. Transl. Med., 2018, 7(1), 3.
[http://dx.doi.org/10.1186/s40169-017-0181-2] [PMID: 29340951]
[7]
Li, Y.H.; Wang, P.P.; Li, X.X.; Yu, C.Y.; Yang, H.; Zhou, J.; Xue, W.W.; Tan, J.; Zhu, F. The human kinome targeted by FDA approved multi-target drugs and combination products: A comparative study from the drug-target interaction network perspective. PLoS One, 2016, 11(11), e0165737.
[http://dx.doi.org/10.1371/journal.pone.0165737] [PMID: 27828998]
[8]
Bieliauskas, A.V.; Pflum, M.K.H. Isoform-selective histone deacetylase inhibitors. Chem. Soc. Rev., 2008, 37(7), 1402-1413.
[http://dx.doi.org/10.1039/b703830p] [PMID: 18568166]
[9]
Kornberg, R.D.; Klug, A. The nucleosome. Sci. Am., 1981, 244(2), 52-64.
[http://dx.doi.org/10.1038/scientificamerican0281-52] [PMID: 7209486]
[10]
Wu, J.; Grunstein, M. 25 years after the nucleosome model: Chromatin modifications. Trends Biochem. Sci., 2000, 25(12), 619-623.
[http://dx.doi.org/10.1016/S0968-0004(00)01718-7] [PMID: 11116189]
[11]
Shirbhate, E.; Patel, P.; Patel, V.K.; Veerasamy, R.; Sharma, P.C.; Rajak, H. The combination of histone deacetylase inhibitors and radiotherapy: A promising novel approach for cancer treatment. Future Oncol., 2020, 16(30), 2457-2469.
[http://dx.doi.org/10.2217/fon-2020-0385] [PMID: 32815411]
[12]
Watson, P.J.; Fairall, L.; Santos, G.M.; Schwabe, J.W.R. Structure of HDAC3 bound to co-repressor and inositol tetraphosphate. Nature, 2012, 481(7381), 335-340.
[http://dx.doi.org/10.1038/nature10728] [PMID: 22230954]
[13]
Muslin, A.; Xing, H. 14-3-3 proteins: Regulation of subcellular localization by molecular interference. Cell. Signal., 2000, 12(11-12), 703-709.
[http://dx.doi.org/10.1016/S0898-6568(00)00131-5] [PMID: 11152955]
[14]
Gao, L.; Cueto, M.A.; Asselbergs, F.; Atadja, P. Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family. J. Biol. Chem., 2002, 277(28), 25748-25755.
[http://dx.doi.org/10.1074/jbc.M111871200] [PMID: 11948178]
[15]
Finnin, M.S.; Donigian, J.R.; Cohen, A.; Richon, V.M.; Rifkind, R.A.; Marks, P.A.; Breslow, R.; Pavletich, N.P. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature, 1999, 401(6749), 188-193.
[http://dx.doi.org/10.1038/43710] [PMID: 10490031]
[16]
Brachmann, C.B.; Sherman, J.M.; Devine, S.E.; Cameron, E.E.; Pillus, L.; Boeke, J.D. The SIR2 gene family, conserved from bacteria to humans, functions in silencing, cell cycle progression, and chromosome stability. Genes Dev., 1995, 9(23), 2888-2902.
[http://dx.doi.org/10.1101/gad.9.23.2888] [PMID: 7498786]
[17]
Qin, J.; Wen, B.; Liang, Y.; Yu, W.; Li, H. Histone modifications and their role in colorectal cancer. Pathol. Oncol. Res., 2020, 26(4), 2023-2033.
[http://dx.doi.org/10.1007/s12253-019-00663-8] [PMID: 31055775]
[18]
Rajak, H.; Singh, A.; Dewangan, P.K.; Patel, V.; Jain, D.K.; Tiwari, S.K.; Veerasamy, R.; Sharma, P.C. Peptide based macrocycles: Selective histone deacetylase inhibitors with antiproliferative activity. Curr. Med. Chem., 2013, 20(14), 1887-1903.
[http://dx.doi.org/10.2174/0929867311320140006] [PMID: 23409715]
[19]
Mottamal, M.; Zheng, S.; Huang, T.; Wang, G. Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules, 2015, 20(3), 3898-3941.
[http://dx.doi.org/10.3390/molecules20033898] [PMID: 25738536]
[20]
Price, S.; Dyke, H.J. Histone deacetylase inhibitors. Expert Opin. Ther. Pat., 2007, 17(7), 745-765.
[http://dx.doi.org/10.1517/13543776.17.7.745]
[21]
Liu, X.H.; Song, H.Y.; Zhang, J.X.; Han, B.C.; Wei, X.N.; Ma, X.H.; Cui, W.K.; Chen, Y.Z. Identifying novel type ZBGs and nonhydroxamate HDAC inhibitors through a SVM based virtual screening approach. Mol. Inform., 2010, 29(5), 407-420.
[http://dx.doi.org/10.1002/minf.200900014] [PMID: 27463196]
[22]
Madsen, A.S.; Kristensen, H.M.E.; Lanz, G.; Olsen, C.A. The effect of various zinc binding groups on inhibition of histone deacetylases 1-11. ChemMedChem, 2014, 9(3), 614-626.
[http://dx.doi.org/10.1002/cmdc.201300433] [PMID: 24375963]
[23]
Park, H.; Kim, S.; Kim, Y.E.; Lim, S.J. A structure-based virtual screening approach toward the discovery of histone deacetylase inhibitors: Identification of promising zincchelating groups. ChemMedChem, 2010, 5(4), 591-597.
[http://dx.doi.org/10.1002/cmdc.200900500] [PMID: 20157916]
[24]
Singh, A.; Patel, P.; Jageshwar; Patel, V.K.; Jain, D.K.; Kamal, M.; Rajak, H. The safety, efficacy and therapeutic potential of histone deacetylase inhibitors with special reference to panobinostat in gastrointestinal tumors: A review of preclinical and clinical studies. Curr. Cancer Drug Targets, 2018, 18(8), 720-736.
[http://dx.doi.org/10.2174/1568009617666170630124643] [PMID: 28669336]
[25]
Singh, A.; Patel, P.; Patel, V.K.; Jain, D.K.; Veerasamy, R.; Sharma, P.C.; Rajak, H. Histone deacetylase inhibitors for the treatment of colorectal cancer: Recent progress and future prospects. Curr. Cancer Drug Targets, 2017, 17(5), 456-466.
[http://dx.doi.org/10.2174/1568009617666170109150134] [PMID: 28067178]
[26]
Patel, P.; Patel, V.K.; Singh, A.; Jawaid, T.; Kamal, M.; Rajak, H. Identification of hydroxamic acid based selective HDAC1 inhibitors: Computer aided drug design studies. Curr. Computeraided Drug Des., 2019, 15(2), 145-166.
[http://dx.doi.org/10.2174/1573409914666180502113135] [PMID: 29732991]
[27]
Singh, A.; Patel, V.K.; Rajak, H. Appraisal of pyrrole as connecting unit in hydroxamic acid based histone deacetylase inhibitors: Synthesis, anticancer evaluation and molecular docking studies. J. Mol. Struct., 2021, 1240, 130590.
[http://dx.doi.org/10.1016/j.molstruc.2021.130590]
[28]
Peng, X.; Sun, Z.; Kuang, P.; Chen, J. Recent progress on HDAC inhibitors with dual targeting capabilities for cancer treatment. Eur. J. Med. Chem., 2020, 208, 112831.
[http://dx.doi.org/10.1016/j.ejmech.2020.112831] [PMID: 32961382]
[29]
Khan, N.; Jeffers, M.; Kumar, S.; Hackett, C.; Boldog, F.; Khramtsov, N.; Qian, X.; Mills, E.; Berghs, S.C.; Carey, N.; Finn, P.W.; Collins, L.S.; Tumber, A.; Ritchie, J.W.; Jensen, P.B.; Lichenstein, H.S.; Sehested, M. Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors. Biochem. J., 2008, 409(2), 581-589.
[http://dx.doi.org/10.1042/BJ20070779] [PMID: 17868033]
[30]
Vaidya, G.N.; Rana, P.; Venkatesh, A.; Chatterjee, D.R.; Contractor, D.; Satpute, D.P.; Nagpure, M.; Jain, A.; Kumar, D. Paradigm shift of “classical” HDAC inhibitors to “hybrid” HDAC inhibitors in therapeutic interventions. Eur. J. Med. Chem., 2021, 209, 112844.
[http://dx.doi.org/10.1016/j.ejmech.2020.112844] [PMID: 33143937]
[31]
Juengel, E.; Makarević, J.; Tsaur, I.; Bartsch, G.; Nelson, K.; Haferkamp, A.; Blaheta, R.A. Resistance after chronic application of the HDAC-inhibitor valproic acid is associated with elevated Akt activation in renal cell carcinoma in vivo. PLoS One, 2013, 8(1), e53100.
[http://dx.doi.org/10.1371/journal.pone.0053100] [PMID: 23372654]
[32]
National Library of Medicine (US). ClinicalTrials.gov identifier: NCT01171924. A Phase IB Expansion study investigating the safety, efficacy, and pharmacokinetics of intravenous CUDC-101 in subjects with advanced head and neck, gastric, breast, liver and non-small cell lung cancer tumors. Available from: https://clinicaltrials.gov/ct2/show/
[33]
Tolcher, A. A phase I study of the safety, pharmacokinetics, and anti-tumor activity of CUDC-101 in patients with advanced solid tumor, NCT00728793, 2018.
[34]
National Library of Medicine (US). Phase I study of CUDC-101 with cisplatin and radiation in subjects with head & neck cancer, NCT01384799, 2018.
[35]
Mueller, S. Fimepinostat in Treating Brain Tumors in Children and Young Adults (PNOC016), NCT03893487, 2022.
[36]
Shulman, S.D. Fimepinostat in treating brain tumors in children and young adults (PNOC016). NCT02909777, 2022.
[37]
National Library of Medicine (US). Study to assess the safety, tolerability and pharmacokinetics of fimepinostat (CUDC-907) in patients with lymphoma, NCT01742988, 2021.
[38]
Aggarwal, R. Hyperpolarized C-13 pyruvate as a biomarker in patients with advanced solid tumor malignancies, NCT02913131, 2022.
[39]
Kummar, S. Study of the safety, pharmacokinetics and efficacy of EDO-S101, in patients with advanced solid tumors, NCT03345485, 2020.
[40]
Hari, P.; Hess, D. Tinostamustine conditioning and autologous stem cell (Titanium1). NCT03687125, 2021.
[41]
Engert, A. Oral histone deacetylase inhibitor 4sc-202 in patients with advanced hematologic malignancies (TOPAS), NCT01344707, 2015.
[42]
Schadendorf, D. Combination with pembrolizumab in patients primary refractory/non-responding to prior anti-PD-1 therapy (Sensitize). NCT03278665, 2022.
[43]
Ma, X.; Ezzeldin, H.H.; Diasio, R.B. Histone deacetylase inhibitors: Current status and overview of recent clinical trials. Drugs, 2009, 69(14), 1911-1934.
[http://dx.doi.org/10.2165/11315680-000000000-00000] [PMID: 19747008]
[44]
Rabal, O.; Sánchez-Arias, J.A.; Cuadrado-Tejedor, M.; de Miguel, I.; Pérez-González, M.; García-Barroso, C.; Ugarte, A.; Estella-Hermoso de Mendoza, A.; Sáez, E.; Espelosin, M.; Ursua, S.; Haizhong, T.; Wei, W.; Musheng, X.; Garcia-Osta, A.; Oyarzabal, J. Design, Synthesis, and biological evaluation of first-in-class dual acting histone deacetylases (HDACs) and phosphodiesterase 5 (PDE5) inhibitors for the treatment of Alzheimer’s disease. J. Med. Chem., 2016, 59(19), 8967-9004.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00908] [PMID: 27606546]
[45]
Fu, R.; Sun, Y.; Sheng, W.; Liao, D. Designing multi-targeted agents: An emerging anticancer drug discovery paradigm. Eur. J. Med. Chem., 2017, 136, 195-211.
[http://dx.doi.org/10.1016/j.ejmech.2017.05.016] [PMID: 28494256]
[46]
Wang, X.X.; Wan, R.Z.; Liu, Z.P. Recent advances in the discovery of potent and selective HDAC6 inhibitors. Eur. J. Med. Chem., 2018, 143, 1406-1418.
[http://dx.doi.org/10.1016/j.ejmech.2017.10.040] [PMID: 29133060]
[47]
Bass, A.K.A.; El-Zoghbi, M.S.; Nageeb, E.S.M.; Mohamed, M.F.A.; Badr, M.; Abuo-Rahma, G.E.D.A. Comprehensive review for anticancer hybridized multitargeting HDAC inhibitors. Eur. J. Med. Chem., 2021, 209, 112904.
[http://dx.doi.org/10.1016/j.ejmech.2020.112904] [PMID: 33077264]
[48]
Suraweera, A.; O’Byrne, K.J.; Richard, D.J. Combination therapy with histone deacetylase inhibitors (HDACi) for the treatment of cancer: Achieving the full therapeutic potential of HDACi. Front. Oncol., 2018, 8, 92.
[http://dx.doi.org/10.3389/fonc.2018.00092] [PMID: 29651407]
[49]
Ranganna, K.; Selvam, C.; Shivachar, A.; Yousefipour, Z. Histone deacetylase inhibitors as multitarget-directed epidrugs in blocking PI3K oncogenic signaling: A polypharmacology approach. Int. J. Mol. Sci., 2020, 21(21), 8198.
[http://dx.doi.org/10.3390/ijms21218198] [PMID: 33147762]
[50]
Ververis, K.; Hiong, A.; Karagiannis, T.C. Histone deacetylase inhibitors (HDACIs): Multitargeted anticancer agents. Biologics, 2013, 7, 47-60.
[http://dx.doi.org/10.2147/BTT.S29965] [PMID: 23459471]
[51]
Liu, T.; Wan, Y.; Xiao, Y.; Xia, C.; Duan, G. Dual-target inhibitors based on HDACs: Novel antitumor agents for cancer therapy. J. Med. Chem., 2020, 63(17), 8977-9002.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00491] [PMID: 32320239]
[52]
Tang, J.; Maddali, K.; Dreis, C.D.; Sham, Y.Y.; Vince, R.; Pommier, Y.; Wang, Z. N-3 hydroxylation of pyrimidine-2,4-diones yields dual inhibitors of HIV reverse transcriptase and integrase. ACS Med. Chem. Lett., 2011, 2(1), 63-67.
[http://dx.doi.org/10.1021/ml1002162] [PMID: 21499541]
[53]
Chen, J.B.; Chern, T.R.; Wei, T.T.; Chen, C.C.; Lin, J.H.; Fang, J.M. Design and synthesis of dual-action inhibitors targeting histone deacetylases and 3-hydroxy-3-methylglutaryl coenzyme A reductase for cancer treatment. J. Med. Chem., 2013, 56(9), 3645-3655.
[http://dx.doi.org/10.1021/jm400179b] [PMID: 23570542]
[54]
Tavera-Mendoza, L.E.; Quach, T.D.; Dabbas, B.; Hudon, J.; Liao, X.; Palijan, A.; Gleason, J.L.; White, J.H. Incorporation of histone deacetylase inhibition into the structure of a nuclear receptor agonist. Proc. Natl. Acad. Sci. USA, 2008, 105(24), 8250-8255.
[http://dx.doi.org/10.1073/pnas.0709279105] [PMID: 18550844]
[55]
Schmidt, J.; Rotter, M.; Weiser, T.; Wittmann, S.; Weizel, L.; Kaiser, A.; Heering, J.; Goebel, T.; Angioni, C.; Wurglics, M.; Paulke, A.; Geisslinger, G.; Kahnt, A.; Steinhilber, D.; Proschak, E.; Merk, D. A dual modulator of farnesoid x receptor and soluble epoxide hydrolase to counter nonalcoholic steatohepatitis. J. Med. Chem., 2017, 60(18), 7703-7724.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00398] [PMID: 28845983]
[56]
Huang, W.; Lv, D.; Yu, H.; Sheng, R.; Kim, S.C.; Wu, P.; Luo, K.; Li, J.; Hu, Y. Dual-target-directed 1,3-diphenylurea derivatives: BACE 1 inhibitor and metal chelator against Alzheimer’s disease. Bioorg. Med. Chem., 2010, 18(15), 5610-5615.
[http://dx.doi.org/10.1016/j.bmc.2010.06.042] [PMID: 20620068]
[57]
Grommes, C.; Landreth, G.E.; Heneka, M.T. Antineoplastic effects of peroxisome proliferatoractivated receptor γ agonists. Lancet Oncol., 2004, 5(7), 419-429.
[http://dx.doi.org/10.1016/S1470-2045(04)01509-8] [PMID: 15231248]
[58]
Theocharis, S.; Margeli, A.; Vielh, P.; Kouraklis, G. Peroxisome proliferator-activated receptor-γ ligands as cell-cycle modulators. Cancer Treat. Rev., 2004, 30(6), 545-554.
[http://dx.doi.org/10.1016/j.ctrv.2004.04.004] [PMID: 15325034]
[59]
Youssef, J.; Badr, M. Peroxisome proliferator-activated receptors and cancer: Challenges and opportunities. Br. J. Pharmacol., 2011, 164(1), 68-82.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01383.x] [PMID: 21449912]
[60]
Aouali, N.; Palissot, V.; El-Khoury, V.; Moussay, E.; Janji, B.; Pierson, S.; Brons, N.H.C.; Kellner, L.; Bosseler, M.; Van Moer, K.; Berchem, G. Peroxisome proliferator-activated receptor γ agonists potentiate the cytotoxic effect of valproic acid in multiple myeloma cells. Br. J. Haematol., 2009, 147(5), 662-671.
[http://dx.doi.org/10.1111/j.1365-2141.2009.07902.x] [PMID: 19793255]
[61]
Chang, T.H.; Szabo, E. Enhanced growth inhibition by combination differentiation therapy with ligands of peroxisome proliferator-activated receptor-gamma and inhibitors of histone deacetylase in adenocarcinoma of the lung. Clin. Cancer Res., 2002, 8(4), 1206-1212.
[PMID: 11948134]
[62]
Tilekar, K.; Hess, J.D.; Upadhyay, N.; Bianco, A.L.; Schweipert, M.; Laghezza, A.; Loiodice, F.; Meyer-Almes, F.J.; Aguilera, R.J.; Lavecchia, A.; C S, R. Thiazolidinedione “Magic Bullets” simultaneously targeting PPARγ and HDACs: Design, synthesis, and investi-gations of their in vitro and in vivo antitumor effects. J. Med. Chem., 2021, 64(10), 6949-6971.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00491] [PMID: 34006099]
[63]
Lin, Y.C.; Lin, J.H.; Chou, C.W.; Chang, Y.F.; Yeh, S.H.; Chen, C.C. Statins increase p21 through inhibition of histone deacetylase activity and release of promoter-associated HDAC1/2. Cancer Res., 2008, 68(7), 2375-2383.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-5807] [PMID: 18381445]
[64]
Istvan, E.S.; Deisenhofer, J. Structural mechanism for statin inhibition of HMG-CoA reductase. Science, 2001, 292(5519), 1160-1164.
[http://dx.doi.org/10.1126/science.1059344] [PMID: 11349148]
[65]
Adorini, L.; Daniel, K.; Penna, G. Vitamin D receptor agonists, cancer and the immune system: An intricate relationship. Curr. Top. Med. Chem., 2006, 6(12), 1297-1301.
[http://dx.doi.org/10.2174/156802606777864890] [PMID: 16848743]
[66]
Masuda, S.; Jones, G. Promise of vitamin D analogues in the treatment of hyperproliferative conditions. Mol. Cancer Ther., 2006, 5(4), 797-808.
[http://dx.doi.org/10.1158/1535-7163.MCT-05-0539] [PMID: 16648549]
[67]
Lamblin, M.; Dabbas, B.; Spingarn, R.; Mendoza-Sanchez, R.; Wang, T.T.; An, B.S.; Huang, D.C.; Kremer, R.; White, J.H.; Gleason, J.L. Vitamin D receptor agonist/histone deacetylase inhibitor molecular hybrids. Bioorg. Med. Chem., 2010, 18(11), 4119-4137.
[http://dx.doi.org/10.1016/j.bmc.2010.03.078] [PMID: 20452225]
[68]
Hideshima, T.; Qi, J.; Paranal, R.M.; Tang, W.; Greenberg, E.; West, N.; Colling, M.E.; Estiu, G.; Mazitschek, R.; Perry, J.A.; Ohguchi, H.; Cottini, F.; Mimura, N.; Görgün, G.; Tai, Y.T.; Richardson, P.G.; Carrasco, R.D.; Wiest, O.; Schreiber, S.L.; Anderson, K.C.; Bradner, J.E. Discovery of selective small-molecule HDAC6 inhibitor for overcoming proteasome inhibitor resistance in multiple myeloma. Proc. Natl. Acad. Sci. USA, 2016, 113(46), 13162-13167.
[http://dx.doi.org/10.1073/pnas.1608067113] [PMID: 27799547]
[69]
Hideshima, T.; Richardson, P.G.; Anderson, K.C. Mechanism of action of proteasome inhibitors and deacetylase inhibitors and the biological basis of synergy in multiple myeloma. Mol. Cancer Ther., 2011, 10(11), 2034-2042.
[http://dx.doi.org/10.1158/1535-7163.MCT-11-0433] [PMID: 22072815]
[70]
Bhatia, S.; Krieger, V.; Groll, M.; Osko, J.D.; Reßing, N.; Ahlert, H.; Borkhardt, A.; Kurz, T.; Christianson, D.W.; Hauer, J.; Hansen, F.K. Discovery of the first-in-class dual histone deacetylase proteasome inhibitor. J. Med. Chem., 2018, 61(22), 10299-10309.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01487] [PMID: 30365892]
[71]
Allison, A.C.; Eugui, E.M. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology, 2000, 47(2-3), 85-118.
[http://dx.doi.org/10.1016/S0162-3109(00)00188-0] [PMID: 10878285]
[72]
Suganuma, K.; Sarwono, A.E.Y.; Mitsuhashi, S.; Jąkalski, M.; Okada, T.; Nthatisi, M.; Yamagishi, J.; Ubukata, M.; Inoue, N. Mycophenolic acid and its derivatives as potential chemotherapeutic agents targeting inosine monophosphate dehydrogenase in Trypanosoma congolense. Antimicrob. Agents Chemother., 2016, 60(7), 4391-4393.
[http://dx.doi.org/10.1128/AAC.02816-15] [PMID: 27139487]
[73]
Chen, L.; Wilson, D.; Jayaram, H.N.; Pankiewicz, K.W. Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylases for cancer treatment. J. Med. Chem., 2007, 50(26), 6685-6691.
[http://dx.doi.org/10.1021/jm070864w] [PMID: 18038969]
[74]
Chen, L.; Petrelli, R.; Gao, G.; Wilson, D.J.; McLean, G.T.; Jayaram, H.N.; Sham, Y.Y.; Pankiewicz, K.W. Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylase based on a cinnamic hydroxamic acid core structure. Bioorg. Med. Chem., 2010, 18(16), 5950-5964.
[http://dx.doi.org/10.1016/j.bmc.2010.06.081] [PMID: 20650640]
[75]
Bai, J.; Liao, C.; Liu, Y.; Qin, X.; Chen, J.; Qiu, Y.; Qin, D.; Li, Z.; Tu, Z.C.; Jiang, S. Structure-based design of potent nicotinamide phosphoribosyltransferase inhibitors with promising in vitro and in vivo antitumor activities. J. Med. Chem., 2016, 59(12), 5766-5779.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00324] [PMID: 27224875]
[76]
Dong, G.; Chen, W.; Wang, X.; Yang, X.; Xu, T.; Wang, P.; Zhang, W.; Rao, Y.; Miao, C.; Sheng, C. Small molecule inhibitors simultaneously targeting cancer metabolism and epigenetics: Discovery of novel nicotinamide phosphoribosyltransferase (NAMPT) and histone deacetylase (HDAC) dual inhibitors. J. Med. Chem., 2017, 60(19), 7965-7983.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00467] [PMID: 28885834]
[77]
Moradei, O.M.; Mallais, T.C.; Frechette, S.; Paquin, I.; Tessier, P.E.; Leit, S.M.; Fournel, M.; Bonfils, C.; Trachy-Bourget, M.C.; Liu, J.; Yan, T.P.; Lu, A.H.; Rahil, J.; Wang, J.; Lefebvre, S.; Li, Z.; Vaisburg, A.F.; Besterman, J.M. Novel aminophenyl benzamide-type histone deacetylase inhibitors with enhanced potency and selectivity. J. Med. Chem., 2007, 50(23), 5543-5546.
[http://dx.doi.org/10.1021/jm701079h] [PMID: 17941625]
[78]
Sitkovsky, M.; Lukashev, D.; Deaglio, S.; Dwyer, K.; Robson, S.C.; Ohta, A. Adenosine A2A receptor antagonists: Blockade of adenosinergic effects and T regulatory cells. Br. J. Pharmacol., 2008, 153(S1), S457-S464.
[http://dx.doi.org/10.1038/bjp.2008.23] [PMID: 18311159]
[79]
Ohta, A. A metabolic immune checkpoint: Adenosine in tumor microenvironment. Front. Immunol., 2016, 7, 109.
[http://dx.doi.org/10.3389/fimmu.2016.00109] [PMID: 27066002]
[80]
Yan, W.; Ling, L.; Wu, Y.; Yang, K.; Liu, R.; Zhang, J.; Zhao, S.; Zhong, G.; Zhao, S.; Jiang, H.; Xie, C.; Cheng, J. Structure-based design of dual-acting compounds targeting adenosine A2A receptor and histone deacetylase as novel tumor immunotherapeutic agents. J. Med. Chem., 2021, 64(22), 16573-16597.
[http://dx.doi.org/10.1021/acs.jmedchem.1c01155] [PMID: 34783558]
[81]
Benek, O.; Korabecny, J.; Soukup, O. A perspective on multi-target drugs for Alzheimers disease. Trends Pharmacol. Sci., 2020, 41(7), 434-445.
[http://dx.doi.org/10.1016/j.tips.2020.04.008] [PMID: 32448557]
[82]
Prati, F.; Cavalli, A.; Bolognesi, M. Navigating the chemical space of multitarget-directed ligands: From hybrids to fragments in Alzheimer’s disease. Molecules, 2016, 21(4), 466.
[http://dx.doi.org/10.3390/molecules21040466] [PMID: 27070562]
[83]
Zhou, N.; Xu, W.; Zhang, Y. Histone deacetylase inhibitors merged with protein tyrosine kinase inhibitors. Drug Discov. Ther., 2015, 9(3), 147-155.
[http://dx.doi.org/10.5582/ddt.2015.01001] [PMID: 26193935]
[84]
Roskoski, R., Jr. Properties of FDA-approved small molecule protein kinase inhibitors: A 2021 update. Pharmacol. Res., 2021, 165, 105463.
[http://dx.doi.org/10.1016/j.phrs.2021.105463] [PMID: 33513356]
[85]
Gao, Y.; Zhang, H.; Lirussi, F.; Garrido, C.; Ye, X.Y.; Xie, T. Dual inhibitors of histone deacetylases and other cancer-related targets: A pharmacological perspective. Biochem. Pharmacol., 2020, 182, 114224.
[http://dx.doi.org/10.1016/j.bcp.2020.114224] [PMID: 32956642]
[86]
Biersack, B.; Polat, S.; Höpfner, M. Anticancer properties of chimeric HDAC and kinase inhibitors. Semin. Cancer Biol., 2020, S1044-579(20), 30223-30226.
[http://dx.doi.org/10.1016/j.semcancer.2020.11.005]
[87]
Luan, Y.; Li, J.; Bernatchez, J.A.; Li, R. Kinase and histone deacetylase hybrid inhibitors for cancer therapy. J. Med. Chem., 2019, 62(7), 3171-3183.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00189] [PMID: 30418766]
[88]
Kim, M.J.; Kim, D.E.; Jeong, I.G.; Choi, J.; Jang, S.; Lee, J.H.; Ro, S.; Hwang, J.J.; Kim, C.S. HDAC inhibitors synergize antiproliferative effect of sorafenib in renal cell carcinoma cells. Anticancer Res., 2012, 32(8), 3161-3168.
[PMID: 22843888]
[89]
Chen, M-C.; Chen, C-H.; Wang, J-C.; Tsai, A-C.; Liou, J-P.; Pan, S-L.; Teng, C-M. The HDAC inhibitor, MPT0E028, enhances erlotinib-induced cell death in EGFR-TKI-resistant NSCLC cells. Cell Death Dis., 2013, 4(9), e810.
[http://dx.doi.org/10.1038/cddis.2013.330] [PMID: 24052078]
[90]
Chen, C.H.; Chen, M.C.; Wang, J.C.; Tsai, A.C.; Chen, C.S.; Liou, J.P.; Pan, S.L.; Teng, C.M. Synergistic interaction between the HDAC inhibitor, MPT0E028, and sorafenib in liver cancer cells in vitro and in vivo. Clin. Cancer Res., 2014, 20(5), 1274-1287.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-3909] [PMID: 24520095]
[91]
Greve, G.; Schiffmann, I.; Pfeifer, D.; Pantic, M.; Schüler, J.; Lübbert, M. The pan-HDAC inhibitor panobinostat acts as a sensitizer for erlotinib activity in EGFR-mutated and -wildtype non-small cell lung cancer cells. BMC Cancer, 2015, 15(1), 947.
[http://dx.doi.org/10.1186/s12885-015-1967-5] [PMID: 26675484]
[92]
Qian, D.Z.; Wang, X.; Kachhap, S.K.; Kato, Y.; Wei, Y.; Zhang, L.; Atadja, P.; Pili, R. The histone deacetylase inhibitor NVP-LAQ824 inhibits angiogenesis and has a greater antitumor effect in combination with the vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584. Cancer Res., 2004, 64(18), 6626-6634.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-0540] [PMID: 15374977]
[93]
Ding, C.; Chen, S.; Zhang, C.; Hu, G.; Zhang, W.; Li, L.; Chen, Y.Z.; Tan, C.; Jiang, Y. Synthesis and investigation of novel 6-(1,2,3-triazol-4-yl)-4-aminoquinazolin derivatives possessing hydroxamic acid moiety for cancer therapy. Bioorg. Med. Chem., 2017, 25(1), 27-37.
[http://dx.doi.org/10.1016/j.bmc.2016.10.006] [PMID: 27769671]
[94]
Zuo, M.; Zheng, Y.W.; Lu, S.M.; Li, Y.; Zhang, S.Q. Synthesis and biological evaluation of N-aryl salicylamides with a hydroxamic acid moiety at 5-position as novel HDAC–EGFR dual inhibitors. Bioorg. Med. Chem., 2012, 20(14), 4405-4412.
[http://dx.doi.org/10.1016/j.bmc.2012.05.034] [PMID: 22698782]
[95]
Cai, X.; Zhai, H.X.; Wang, J.; Forrester, J.; Qu, H.; Yin, L.; Lai, C.J.; Bao, R.; Qian, C. Discovery of 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDc-101) as a potent multi-acting HDAC, EGFR, and HER2 inhibitor for the treatment of cancer. J. Med. Chem., 2010, 53(5), 2000-2009.
[http://dx.doi.org/10.1021/jm901453q] [PMID: 20143778]
[96]
Jechlinger, M.; Sommer, A.; Moriggl, R.; Seither, P.; Kraut, N.; Capodiecci, P.; Donovan, M.; Cordon-Cardo, C.; Beug, H.; Grünert, S. Autocrine PDGFR signaling promotes mammary cancer metastasis. J. Clin. Invest., 2006, 116(6), 1561-1570.
[http://dx.doi.org/10.1172/JCI24652] [PMID: 16741576]
[97]
Patel, H.; Chuckowree, I.; Coxhead, P.; Guille, M.; Wang, M.; Zuckermann, A.; Williams, R.S.B.; Librizzi, M.; Paranal, R.M.; Bradner, J.E.; Spencer, J. Synthesis of hybrid anticancer agents based on kinase and histone deacetylase inhibitors. MedChemComm, 2014, 5(12), 1829-1833.
[http://dx.doi.org/10.1039/C4MD00211C]
[98]
Viola, D.; Valerio, L.; Molinaro, E.; Agate, L.; Bottici, V.; Biagini, A.; Lorusso, L.; Cappagli, V.; Pieruzzi, L.; Giani, C.; Sabini, E.; Passannati, P.; Puleo, L.; Matrone, A.; Pontillo-Contillo, B.; Battaglia, V.; Mazzeo, S.; Vitti, P.; Elisei, R. Treatment of advanced thyroid cancer with targeted therapies: Ten years of experience. Endocr. Relat. Cancer, 2016, 23(4), R185-R205.
[http://dx.doi.org/10.1530/ERC-15-0555] [PMID: 27207700]
[99]
Peng, F.W.; Wu, T.T.; Ren, Z.W.; Xue, J.Y.; Shi, L. Hybrids from 4-anilinoquinazoline and hydroxamic acid as dual inhibitors of vascular endothelial growth factor receptor-2 and histone deacetylase. Bioorg. Med. Chem. Lett., 2015, 25(22), 5137-5141.
[http://dx.doi.org/10.1016/j.bmcl.2015.10.006] [PMID: 26475519]
[100]
Ding, C.; Li, D.; Wang, Y.W.; Han, S.S.; Gao, C.M.; Tan, C.Y.; Jiang, Y.Y. Discovery of ErbB/HDAC inhibitors by combining the core pharmacophores of HDAC inhibitor vorinostat and kinase inhibitors vandetanib, BMS-690514, neratinib, and TAK-285. Chin. Chem. Lett., 2017, 28(6), 1220-1227.
[http://dx.doi.org/10.1016/j.cclet.2017.01.003]
[101]
Brotelle, T.; Bay, J.O. Pazopanib for treatment of renal cell carcinoma and soft tissue sarcomas. Bull. Cancer, 2014, 101(6), 641-646.
[http://dx.doi.org/10.1684/bdc.2014.1981] [PMID: 24977453]
[102]
Zang, J.; Liang, X.; Huang, Y.; Jia, Y.; Li, X.; Xu, W.; Chou, C.J.; Zhang, Y. Discovery of novel pazopanib-based HDAC and VEGFR dual inhibitors targeting cancer epigenetics and angiogenesis simultaneously. J. Med. Chem., 2018, 61(12), 5304-5322.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00384] [PMID: 29787262]
[103]
Zhang, M.; Jang, H.; Nussinov, R. PI3K inhibitors: Review and new strategies. Chem. Sci. (Camb.), 2020, 11(23), 5855-5865.
[http://dx.doi.org/10.1039/D0SC01676D] [PMID: 32953006]
[104]
Yamada, T.; Horinaka, M.; Shinnoh, M.; Yoshioka, T.; Miki, T.; Sakai, T. A novel HDAC inhibitor OBP-801 and a PI3K inhibitor LY294002 synergistically induce apoptosis via the suppression of survivin and XIAP in renal cell carcinoma. Int. J. Oncol., 2013, 43(4), 1080-1086.
[http://dx.doi.org/10.3892/ijo.2013.2042] [PMID: 23900601]
[105]
Yoshioka, T.; Yogosawa, S.; Yamada, T.; Kitawaki, J.; Sakai, T. Combination of a novel HDAC inhibitor OBP-801/YM753 and a PI3K inhibitor LY294002 synergistically induces apoptosis in human endometrial carcinoma cells due to increase of Bim with accumulation of ROS. Gynecol. Oncol., 2013, 129(2), 425-432.
[http://dx.doi.org/10.1016/j.ygyno.2013.02.008] [PMID: 23403163]
[106]
Yun, F.; Cheng, C.; Ullah, S.; Yuan, Q. Design, synthesis and biological evaluation of novel histone deacetylase1/2 (HDAC1/2) and cyclin-dependent Kinase2 (CDK2) dual inhibitors against malignant cancer. Eur. J. Med. Chem., 2020, 198, 112322.
[http://dx.doi.org/10.1016/j.ejmech.2020.112322] [PMID: 32361064]
[107]
Cheng, C.; Yun, F.; Ullah, S.; Yuan, Q. Discovery of novel cyclin-dependent kinase (CDK) and histone deacetylase (HDAC) dual inhibitors with potent in vitro and in vivo anticancer activity. Eur. J. Med. Chem., 2020, 189, 112073.
[http://dx.doi.org/10.1016/j.ejmech.2020.112073] [PMID: 31991336]
[108]
Guerra, B.; Issinger, O.G. Protein kinase CK2 in human diseases. Curr. Med. Chem., 2008, 15(19), 1870-1886.
[http://dx.doi.org/10.2174/092986708785132933] [PMID: 18691045]
[109]
Laurence, A.; Pesu, M.; Silvennoinen, O.; O’Shea, J. JAK kinases in health and disease: An update. Open Rheumatol. J., 2012, 6(1), 232-244.
[http://dx.doi.org/10.2174/1874312901206010232] [PMID: 23028408]
[110]
Gao, S.; Chen, C.; Wang, L.; Hong, L.; Wu, J.; Dong, P.; Yu, F. Histone deacetylases inhibitor sodium butyrate inhibits JAK2/STAT signaling through upregulation of SOCS1 and SOCS3 mediated by HDAC8 inhibition in myeloproliferative neoplasms. Exp. Hematol., 2013, 41(3), 261-270.e4.
[http://dx.doi.org/10.1016/j.exphem.2012.10.012] [PMID: 23111066]
[111]
Quintás-Cardama, A.; Kantarjian, H.; Estrov, Z.; Borthakur, G.; Cortes, J.; Verstovsek, S. Therapy with the histone deacetylase inhibitor pracinostat for patients with myelofibrosis. Leuk. Res., 2012, 36(9), 1124-1127.
[http://dx.doi.org/10.1016/j.leukres.2012.03.003] [PMID: 22475363]
[112]
Yang, E.G.; Mustafa, N.; Tan, E.C.; Poulsen, A.; Ramanujulu, P.M.; Chng, W.J.; Yen, J.J.Y.; Dymock, B.W. Design and synthesis of janus kinase 2 (JAK2) and histone deacetlyase (HDAC) bispecific inhibitors based on pacritinib and evidence of dual pathway inhibition in hematological cell lines. J. Med. Chem., 2016, 59(18), 8233-8262.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00157] [PMID: 27541357]
[113]
Ning, C.Q.; Lu, C.; Hu, L.; Bi, Y.J.; Yao, L.; He, Y.J.; Liu, L.F.; Liu, X.Y.; Yu, N.F. Macrocyclic compounds as anti-cancer agents: Design and synthesis of multi-acting inhibitors against HDAC, FLT3 and JAK2. Eur. J. Med. Chem., 2015, 95, 104-115.
[http://dx.doi.org/10.1016/j.ejmech.2015.03.034] [PMID: 25800646]
[114]
Rebocho, A.P.; Marais, R. ARAF acts as a scaffold to stabilize BRAF:CRAF heterodimers. Oncogene, 2013, 32(26), 3207-3212.
[http://dx.doi.org/10.1038/onc.2012.330] [PMID: 22926515]
[115]
Keating, G.M. Sorafenib: A review in hepatocellular carcinoma. Target. Oncol., 2017, 12(2), 243-253.
[http://dx.doi.org/10.1007/s11523-017-0484-7] [PMID: 28299600]
[116]
Geng, A.; Cui, H.; Zhang, L.; Chen, X.; Li, H.; Lu, T.; Zhu, Y. Discovery of novel phenoxybenzamide analogues as Raf/HDAC dual inhibitors. Bioorg. Med. Chem. Lett., 2019, 29(13), 1605-1608.
[http://dx.doi.org/10.1016/j.bmcl.2019.04.047] [PMID: 31053508]
[117]
Borgo, C.; Ruzzene, M. Role of protein kinase CK2 in antitumor drug resistance. J. Exp. Clin. Cancer Res., 2019, 38(1), 287.
[http://dx.doi.org/10.1186/s13046-019-1292-y] [PMID: 31277672]
[118]
Martínez, R.; Di Geronimo, B.; Pastor, M.; Zapico, J.M.; Coderch, C.; Panchuk, R.; Skorokhyd, N.; Maslyk, M.; Ramos, A.; de Pascual-Teresa, B. Multitarget anticancer agents based on histone deacetylase and protein kinase CK2 inhibitors. Molecules, 2020, 25(7), 1497.
[http://dx.doi.org/10.3390/molecules25071497] [PMID: 32218358]
[119]
Rangasamy, L.; Ortín, I.; Zapico, J.M.; Coderch, C.; Ramos, A.; de Pascual-Teresa, B. de Pascual-Teresa, B. New dual CK2/HDAC1 inhibitors with nanomolar inhibitory activity against both enzymes. ACS Med. Chem. Lett., 2020, 11(5), 713-719.
[http://dx.doi.org/10.1021/acsmedchemlett.9b00561] [PMID: 32435375]
[120]
Zhang, Y.; Xia, M.; Jin, K.; Wang, S.; Wei, H.; Fan, C.; Wu, Y.; Li, X.; Li, X.; Li, G.; Zeng, Z.; Xiong, W. Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities. Mol. Cancer, 2018, 17(1), 45.
[http://dx.doi.org/10.1186/s12943-018-0796-y] [PMID: 29455668]
[121]
Lu, D.; Yan, J.; Wang, L.; Liu, H.; Zeng, L.; Zhang, M.; Duan, W.; Ji, Y.; Cao, J.; Geng, M.; Shen, A.; Hu, Y. Design, synthesis, and biological evaluation of the first cmet/hdac inhibitors based on pyridazinone derivatives. ACS Med. Chem. Lett., 2017, 8(8), 830-834.
[http://dx.doi.org/10.1021/acsmedchemlett.7b00172] [PMID: 28835797]
[122]
Dai, S.; Zhou, Z.; Chen, Z.; Xu, G.; Chen, Y. Fibroblast growth factor receptors (FGFRs): Structures and small molecule inhibitors. Cells, 2019, 8(6), 614.
[http://dx.doi.org/10.3390/cells8060614] [PMID: 31216761]
[123]
Liu, J.; Qian, C.; Zhu, Y.; Cai, J.; He, Y.; Li, J.; Wang, T.; Zhu, H.; Li, Z.; Li, W.; Hu, L. Design, synthesis and evaluate of novel dual FGFR1 and HDAC inhibitors bearing an indazole scaffold. Bioorg. Med. Chem., 2018, 26(3), 747-757.
[http://dx.doi.org/10.1016/j.bmc.2017.12.041] [PMID: 29317150]
[124]
Shuai, W.; Wang, G.; Zhang, Y.; Bu, F.; Zhang, S.; Miller, D.D.; Li, W.; Ouyang, L.; Wang, Y. Recent progress on tubulin inhibitors with dual targeting capabilities for cancer therapy. J. Med. Chem., 2021, 64(12), 7963-7990.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00100] [PMID: 34101463]
[125]
Wang, Y.; Sun, M.; Wang, Y.; Qin, J.; Zhang, Y.; Pang, Y.; Yao, Y.; Yang, H.; Duan, Y. Discovery of novel tubulin/HDAC dual-targeting inhibitors with strong antitumor and antiangiogenic potency. Eur. J. Med. Chem., 2021, 225, 113790.
[http://dx.doi.org/10.1016/j.ejmech.2021.113790] [PMID: 34454126]
[126]
Lee, H.Y.; Lee, J.F.; Kumar, S.; Wu, Y.W.; HuangFu, W.C.; Lai, M.J.; Li, Y.H.; Huang, H.L.; Kuo, F.C.; Hsiao, C.J.; Cheng, C.C.; Yang, C.R.; Liou, J.P. 3-Aroylindoles display antitumor activity in vitro and in vivo: Effects of N1-substituents on biological activity. Eur. J. Med. Chem., 2017, 125, 1268-1278.
[http://dx.doi.org/10.1016/j.ejmech.2016.11.033] [PMID: 27886544]
[127]
Schmitt, F.; Gosch, L.; Dittmer, A.; Rothemund, M.; Mueller, T.; Schobert, R.; Biersack, B.; Volkamer, A.; Höpfner, M. Oxazole-bridged Combretastatin A-4 derivatives with tethered hydroxamic acids: Structure–activity relations of new inhibitors of HDAC and/or tubulin function. Int. J. Mol. Sci., 2019, 20(2), 383.
[http://dx.doi.org/10.3390/ijms20020383] [PMID: 30658435]
[128]
Mourad, A.A.E.; Mourad, M.A.E.; Jones, P.G. Novel HDAC/tubulin dual inhibitor: Design, synthesis and docking studies of α-phthalimido-chalcone hybrids as potential anticancer agents with apoptosis-inducing activity. Drug Des. Devel. Ther., 2020, 14, 3111-3130.
[http://dx.doi.org/10.2147/DDDT.S256756] [PMID: 32848361]
[129]
Patel, V.K.; Singh, A.; Jain, D.K.; Patel, P.; Veerasamy, R.; Sharma, P.C.; Rajak, H. Combretastatin A-4 based thiophene derivatives as antitumor agent: Development of structure activity correlation model using 3D-QSAR, pharmacophore and docking studies. Future J. Pharm. Sci., 2017, 3(2), 71-78.
[http://dx.doi.org/10.1016/j.fjps.2017.03.003]
[130]
Patel, V.K.; Rajak, H. Development of structure activity correlation model on aroylindole derivatives as anticancer agents. Lett. Drug Des. Discov., 2018, 15(2), 143-153.
[http://dx.doi.org/10.2174/1570180814666170823161751]
[131]
Zhang, X.; Kong, Y.; Zhang, J.; Su, M.; Zhou, Y.; Zang, Y.; Li, J.; Chen, Y.; Fang, Y.; Zhang, X.; Lu, W. Design, synthesis and biological evaluation of colchicine derivatives as novel tubulin and histone deacetylase dual inhibitors. Eur. J. Med. Chem., 2015, 95, 127-135.
[http://dx.doi.org/10.1016/j.ejmech.2015.03.035] [PMID: 25805446]
[132]
Zhang, X.; Zhang, J.; Su, M.; Zhou, Y.; Chen, Y.; Li, J.; Lu, W. Design, synthesis and biological evaluation of 4′-demethyl-4-deoxypodophyllotoxin derivatives as novel tubulin and histone deacetylase dual inhibitors. RSC Advances, 2014, 4(76), 40444-40448.
[http://dx.doi.org/10.1039/C4RA05508J]
[133]
Patel, V.K.; Rajak, H. Significance of amino group substitution at combretastatin a-4 and phenstatin analogs. Lett. Drug Des. Discov., 2016, 13(9), 943-951.
[http://dx.doi.org/10.2174/1570180813666160517163444]
[134]
Patel, V.K.; Rajak, H. Structural investigations of aroylindole derivatives through 3D-QSAR and multiple pharmacophore modeling for the search of novel colchicines inhibitor. Lett. Drug Des. Discov., 2021, 18(2), 131-142.
[http://dx.doi.org/10.2174/1570180817999200905092444]
[135]
Lamaa, D.; Lin, H.P.; Zig, L.; Bauvais, C.; Bollot, G.; Bignon, J.; Levaique, H.; Pamlard, O.; Dubois, J.; Ouaissi, M.; Souce, M.; Kasselouri, A.; Saller, F.; Borgel, D.; Jayat-Vignoles, C.; Al-Mouhammad, H.; Feuillard, J.; Benihoud, K.; Alami, M.; Hamze, A. Design and synthesis of tubulin and histone deacetylase inhibitor based on iso-Combretastatin A-4. J. Med. Chem., 2018, 61(15), 6574-6591.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00050] [PMID: 30004697]
[136]
Wang, J.C. Cellular roles of DNA topoisomerases: A molecular perspective. Nat. Rev. Mol. Cell Biol., 2002, 3(6), 430-440.
[http://dx.doi.org/10.1038/nrm831] [PMID: 12042765]
[137]
Guerrant, W.; Patil, V.; Canzoneri, J.C.; Oyelere, A.K. Dual targeting of histone deacetylase and topoisomerase II with novel bifunctional inhibitors. J. Med. Chem., 2012, 55(4), 1465-1477.
[http://dx.doi.org/10.1021/jm200799p] [PMID: 22260166]
[138]
Zhang, X.; Bao, B.; Yu, X.; Tong, L.; Luo, Y.; Huang, Q.; Su, M.; Sheng, L.; Li, J.; Zhu, H.; Yang, B.; Zhang, X.; Chen, Y.; Lu, W. The discovery and optimization of novel dual inhibitors of topoisomerase II and histone deacetylase. Bioorg. Med. Chem., 2013, 21(22), 6981-6995.
[http://dx.doi.org/10.1016/j.bmc.2013.09.023] [PMID: 24095018]
[139]
Guerrant, W.; Patil, V.; Canzoneri, J.C.; Yao, L.P.; Hood, R.; Oyelere, A.K. Dual-acting histone deacetylase-topoisomerase I inhibitors. Bioorg. Med. Chem. Lett., 2013, 23(11), 3283-3287.
[http://dx.doi.org/10.1016/j.bmcl.2013.03.108] [PMID: 23622981]
[140]
Cincinelli, R.; Musso, L.; Artali, R.; Guglielmi, M.B.; La Porta, I.; Melito, C.; Colelli, F.; Cardile, F.; Signorino, G.; Fucci, A.; Frusciante, M.; Pisano, C.; Dallavalle, S. Hybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents. PLoS One, 2018, 13(10), e0205018.
[http://dx.doi.org/10.1371/journal.pone.0205018] [PMID: 30300374]
[141]
Diyabalanage, H.V.K.; Granda, M.L.; Hooker, J.M. Combination therapy: Histone deacetylase inhibitors and platinum-based chemotherapeutics for cancer. Cancer Lett., 2013, 329(1), 1-8.
[http://dx.doi.org/10.1016/j.canlet.2012.09.018] [PMID: 23032720]
[142]
Xie, R.; Li, Y.; Tang, P.; Yuan, Q. Rational design, synthesis and preliminary antitumor activity evaluation of a chlorambucil derivative with potent DNA/HDAC dual-targeting inhibitory activity. Bioorg. Med. Chem. Lett., 2017, 27(18), 4415-4420.
[http://dx.doi.org/10.1016/j.bmcl.2017.08.011] [PMID: 28818449]
[143]
Griffith, D.; Morgan, M.P.; Marmion, C.J. A novel anti-cancer bifunctional platinum drug candidate with dual DNA binding and histone deacetylase inhibitory activity. Chem. Commun. (Camb.), 2009, 28(44), 6735-6737.
[http://dx.doi.org/10.1039/b916715c] [PMID: 19885462]
[144]
Almotairy, A.R.Z.; Gandin, V.; Morrison, L.; Marzano, C.; Montagner, D.; Erxleben, A. Antitumor platinum(IV) derivatives of carboplatin and the histone deacetylase inhibitor 4-phenylbutyric acid. J. Inorg. Biochem., 2017, 177, 1-7.
[http://dx.doi.org/10.1016/j.jinorgbio.2017.09.009] [PMID: 28918353]
[145]
Fujisawa, T.; Filippakopoulos, P. Functions of bromodomain-containing proteins and their roles in homeostasis and cancer. Nat. Rev. Mol. Cell Biol., 2017, 18(4), 246-262.
[http://dx.doi.org/10.1038/nrm.2016.143] [PMID: 28053347]
[146]
Lovén, J.; Hoke, H.A.; Lin, C.Y.; Lau, A.; Orlando, D.A.; Vakoc, C.R.; Bradner, J.E.; Lee, T.I.; Young, R.A. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell, 2013, 153(2), 320-334.
[http://dx.doi.org/10.1016/j.cell.2013.03.036] [PMID: 23582323]
[147]
Chesi, M.; Matthews, G.M.; Garbitt, V.M.; Palmer, S.E.; Shortt, J.; Lefebure, M.; Stewart, A.K.; Johnstone, R.W.; Bergsagel, P.L. Drug response in a genetically engineered mouse model of multiple myeloma is predictive of clinical efficacy. Blood, 2012, 120(2), 376-385.
[http://dx.doi.org/10.1182/blood-2012-02-412783] [PMID: 22451422]
[148]
He, S.; Dong, G.; Li, Y.; Wu, S.; Wang, W.; Sheng, C. Potent dual BET/HDAC inhibitors for efficient treatment of pancreatic cancer. Angew. Chem. Int. Ed., 2020, 59(8), 3028-3032.
[http://dx.doi.org/10.1002/anie.201915896] [PMID: 31943585]
[149]
Zhang, Z.; Hou, S.; Chen, H.; Ran, T.; Jiang, F.; Bian, Y.; Zhang, D.; Zhi, Y.; Wang, L.; Zhang, L.; Li, H.; Zhang, Y.; Tang, W.; Lu, T.; Chen, Y. Targeting epigenetic reader and eraser: Rational design, synthesis and in vitro evaluation of dimethylisoxazoles derivatives as BRD4/HDAC dual inhibitors. Bioorg. Med. Chem. Lett., 2016, 26(12), 2931-2935.
[http://dx.doi.org/10.1016/j.bmcl.2016.04.034] [PMID: 27142751]
[150]
Pan, Z.; Li, X.; Wang, Y.; Jiang, Q.; Jiang, L.; Zhang, M.; Zhang, N.; Wu, F.; Liu, B.; He, G. Discovery of thieno[2,3-d]pyrimidine-based hydroxamic acid derivatives as bromodomain-containing protein 4/histone deacetylase dual inhibitors induce autophagic cell death in colorectal carcinoma cells. J. Med. Chem., 2020, 63(7), 3678-3700.
[http://dx.doi.org/10.1021/acs.jmedchem.9b02178] [PMID: 32153186]
[151]
Shao, M.; He, L.; Zheng, L.; Huang, L.; Zhou, Y.; Wang, T.; Chen, Y.; Shen, M.; Wang, F.; Yang, Z.; Chen, L. Structure-based design, synthesis and in vitro antiproliferative effects studies of novel dual BRD4/HDAC inhibitors. Bioorg. Med. Chem. Lett., 2017, 27(17), 4051-4055.
[http://dx.doi.org/10.1016/j.bmcl.2017.07.054] [PMID: 28765013]
[152]
Hoter, A.; El-Sabban, M.; Naim, H. The HSP90 family: Structure, regulation, function, and implications in health and disease. Int. J. Mol. Sci., 2018, 19(9), 2560.
[http://dx.doi.org/10.3390/ijms19092560] [PMID: 30158430]
[153]
Wu, Y.W.; Chao, M.W.; Tu, H.J.; Chen, L.C.; Hsu, K.C.; Liou, J.P.; Yang, C.R.; Yen, S.C.; Huang Fu, W.C.; Pan, S.L. A novel dual HDAC and HSP90 inhibitor, MPT0G449, downregulates oncogenic pathways in human acute leukemia in vitro and in vivo. Oncogenesis, 2021, 10(5), 39.
[http://dx.doi.org/10.1038/s41389-021-00331-0] [PMID: 33986242]
[154]
Ojha, R.; Huang, H.L.; HuangFu, W.C.; Wu, Y.W.; Nepali, K.; Lai, M.J.; Su, C.J.; Sung, T.Y.; Chen, Y.L.; Pan, S.L.; Liou, J.P. 1-Aroylindoline-hydroxamic acids as anticancer agents, inhibitors of HSP90 and HDAC. Eur. J. Med. Chem., 2018, 150, 667-677.
[http://dx.doi.org/10.1016/j.ejmech.2018.03.006] [PMID: 29567459]
[155]
Mehndiratta, S.; Lin, M.H.; Wu, Y.W.; Chen, C.H.; Wu, T.Y.; Chuang, K.H.; Chao, M.W.; Chen, Y.Y.; Pan, S.L.; Chen, M.C.; Liou, J.P. N-alkyl-hydroxybenzoyl anilide hydroxamates as dual inhibitors of HDAC and HSP90, downregulating IFN-γ induced PD-L1 expression. Eur. J. Med. Chem., 2020, 185, 111725.
[http://dx.doi.org/10.1016/j.ejmech.2019.111725] [PMID: 31655430]
[156]
Yao, L.; Ohlson, S.; Dymock, B.W. Design and synthesis of triple inhibitors of janus kinase (JAK), histone deacetylase (HDAC) and Heat Shock Protein 90 (HSP90). Bioorg. Med. Chem. Lett., 2018, 28(8), 1357-1362.
[http://dx.doi.org/10.1016/j.bmcl.2018.03.009] [PMID: 29545103]
[157]
Overall, C.M.; Kleifeld, O. Validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat. Rev. Cancer, 2006, 6(3), 227-239.
[http://dx.doi.org/10.1038/nrc1821] [PMID: 16498445]
[158]
Egeblad, M.; Werb, Z. New functions for the matrix metalloproteinases in cancer progression. Nat. Rev. Cancer, 2002, 2(3), 161-174.
[http://dx.doi.org/10.1038/nrc745] [PMID: 11990853]
[159]
Adhikari, N.; Mukherjee, A.; Saha, A.; Jha, T. Arylsulfonamides and selectivity of matrix metalloproteinase-2: An overview. Eur. J. Med. Chem., 2017, 129, 72-109.
[http://dx.doi.org/10.1016/j.ejmech.2017.02.014] [PMID: 28219048]
[160]
Amin, S.A.; Adhikari, N.; Jha, T. Is dual inhibition of metalloenzymes HDAC-8 and MMP-2 a potential pharmacological target to combat hematological malignancies? Pharmacol. Res., 2017, 122, 8-19.
[http://dx.doi.org/10.1016/j.phrs.2017.05.002] [PMID: 28501516]
[161]
Klein, G.; Vellenga, E.; Fraaije, M.W.; Kamps, W.A.; de Bont, E.S.J.M. The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia. Crit. Rev. Oncol. Hematol., 2004, 50(2), 87-100.
[http://dx.doi.org/10.1016/j.critrevonc.2003.09.001] [PMID: 15157658]
[162]
Cheng, X.C.; Wang, R.L.; Dong, Z.K.; Li, J.; Li, Y.Y.; Li, R.R. Design, synthesis and evaluation of novel metalloproteinase inhibitors based on l-tyrosine scaffold. Bioorg. Med. Chem., 2012, 20(19), 5738-5744.
[http://dx.doi.org/10.1016/j.bmc.2012.08.014] [PMID: 22967811]
[163]
Li, X.; Wang, J.; Li, J.; Wu, J.; Li, Y.; Zhu, H.; Fan, R.; Xu, W. Novel aminopeptidase N inhibitors derived from antineoplaston AS2–5 (Part I). Bioorg. Med. Chem., 2009, 17(8), 3053-3060.
[http://dx.doi.org/10.1016/j.bmc.2009.02.063] [PMID: 19329328]
[164]
Li, X.; Wang, Y.; Wu, J.; Li, Y.; Wang, Q.; Xu, W. Novel aminopeptidase N inhibitors derived from antineoplaston AS2–5 (Part II). Bioorg. Med. Chem., 2009, 17(8), 3061-3071.
[http://dx.doi.org/10.1016/j.bmc.2009.03.017] [PMID: 19339187]
[165]
Wang, Y.; Yang, L.; Hou, J.; Zou, Q.; Gao, Q.; Yao, W.; Yao, Q.; Zhang, J. Hierarchical virtual screening of the dual MMP-2/HDAC-6 inhibitors from natural products based on pharmacophore models and molecular docking. J. Biomol. Struct. Dyn., 2019, 37(3), 649-670.
[http://dx.doi.org/10.1080/07391102.2018.1434833] [PMID: 29380672]
[166]
Fischer, S.M.; Hawk, E.T.; Lubet, R.A. Coxibs and other nonsteroidal anti-inflammatory drugs in animal models of cancer chemoprevention. Cancer Prev. Res. (Phila.), 2011, 4(11), 1728-1735.
[http://dx.doi.org/10.1158/1940-6207.CAPR-11-0166] [PMID: 21778329]
[167]
Zang, J.; Shi, B.; Liang, X.; Gao, Q.; Xu, W.; Zhang, Y. Development of N -hydroxycinnamamide-based HDAC inhibitors with improved HDAC inhibitory activity and in vitro antitumor activity. Bioorg. Med. Chem., 2017, 25(9), 2666-2675.
[http://dx.doi.org/10.1016/j.bmc.2016.12.001] [PMID: 28336407]
[168]
Chang, M.S. Tamoxifen resistance in breast cancer. Biomol. Ther. (Seoul), 2012, 20(3), 256-267.
[http://dx.doi.org/10.4062/biomolther.2012.20.3.256] [PMID: 24130921]
[169]
Hodges-Gallagher, L.; Valentine, C.D.; Bader, S.E.; Kushner, P.J. Inhibition of histone deacetylase enhances the anti-proliferative action of antiestrogens on breast cancer cells and blocks tamoxifen-induced proliferation of uterine cells. Breast Cancer Res. Treat., 2007, 105(3), 297-309.
[http://dx.doi.org/10.1007/s10549-006-9459-6] [PMID: 17186358]
[170]
Ulm, M.; Ramesh, A.V.; McNamara, K.M.; Ponnusamy, S.; Sasano, H.; Narayanan, R. Therapeutic advances in hormone-dependent cancers: Focus on prostate, breast and ovarian cancers. Endocr. Connect., 2019, 8(2), R10-R26.
[http://dx.doi.org/10.1530/EC-18-0425] [PMID: 30640710]
[171]
Yang, X.; Phillips, D.L.; Ferguson, A.T.; Nelson, W.G.; Herman, J.G.; Davidson, N.E. Synergistic activation of functional estrogen receptor (ER)-alpha by DNA methyltransferase and histone deacetylase inhibition in human ER-alpha-negative breast cancer cells. Cancer Res., 2001, 61(19), 7025-7029.
[PMID: 11585728]
[172]
Sabnis, G.J.; Goloubeva, O.; Chumsri, S.; Nguyen, N.; Sukumar, S.; Brodie, A.M.H. Functional activation of the estrogen receptor-α and aromatase by the HDAC inhibitor entinostat sensitizes ER-negative tumors to letrozole. Cancer Res., 2011, 71(5), 1893-1903.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-2458] [PMID: 21245100]
[173]
Restall, C.; Doherty, J.; Liu, H.B.; Genovese, R.; Paiman, L.; Byron, K.A.; Anderson, R.L.; Dear, A.E. A novel histone deacetylase inhibitor augments tamoxifen-mediated attenuation of breast carcinoma growth. Int. J. Cancer, 2009, 125(2), 483-487.
[http://dx.doi.org/10.1002/ijc.24350] [PMID: 19330834]
[174]
Gryder, B.E.; Rood, M.K.; Johnson, K.A.; Patil, V.; Raftery, E.D.; Yao, L.P.D.; Rice, M.; Azizi, B.; Doyle, D.F.; Oyelere, A.K. Histone deacetylase inhibitors equipped with estrogen receptor modulation activity. J. Med. Chem., 2013, 56(14), 5782-5796.
[http://dx.doi.org/10.1021/jm400467w] [PMID: 23786452]
[175]
Mendoza-Sanchez, R.; Cotnoir-White, D.; Kulpa, J.; Jutras, I.; Pottel, J.; Moitessier, N.; Mader, S.; Gleason, J.L. Design, synthesis and evaluation of antiestrogen and histone deacetylase inhibitor molecular hybrids. Bioorg. Med. Chem., 2015, 23(24), 7597-7606.
[http://dx.doi.org/10.1016/j.bmc.2015.11.005] [PMID: 26613635]
[176]
Tang, C.; Li, C.; Zhang, S.; Hu, Z.; Wu, J.; Dong, C.; Huang, J.; Zhou, H.B. Novel bioactive hybrid compound dual targeting estrogen receptor and histone deacetylase for the treatment of breast cancer. J. Med. Chem., 2015, 58(11), 4550-4572.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00099] [PMID: 25993269]
[177]
Duan, R.; Du, W.; Guo, W. EZH2: A novel target for cancer treatment. J. Hematol. Oncol., 2020, 13(1), 104.
[http://dx.doi.org/10.1186/s13045-020-00937-8] [PMID: 32723346]
[178]
Romanelli, A.; Stazi, G.; Fioravanti, R.; Zwergel, C.; Di Bello, E.; Pomella, S.; Perrone, C.; Battistelli, C.; Strippoli, R.; Tripodi, M.; del Bufalo, D.; Rota, R.; Trisciuoglio, D.; Mai, A.; Valente, S. Design of first-in-class dual EZH2/HDAC inhibitor: Biochemical activity and biological evaluation in cancer cells. ACS Med. Chem. Lett., 2020, 11(5), 977-983.
[http://dx.doi.org/10.1021/acsmedchemlett.0c00014] [PMID: 32435414]

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