Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Author(s): Rangan Mitra and Senthil Raja Ayyannan*

DOI: 10.2174/1871520622666220421092414

DownloadDownload PDF Flyer Cite As
Role of Lysine-specific Demethylase 1 and Its Small Molecule Inhibitors in Glioblastoma Multiforme Therapy

Page: [3062 - 3085] Pages: 24

  • * (Excluding Mailing and Handling)

Abstract

Glioblastoma multiforme (GBM) is among the most critical and aggressive carcinomas of CNS, characterised by poor prognosis, low survival rate and difficult clinical correlations. Current treatment opportunities have proved to be insufficient due to high chemoresistance and relapse of the disease with enhanced malignancy. Molecular diagnostics and epigenetic profiling of GBM have discovered several signaling pathways and cellular mediators, which play key roles in triggering GBM phenotypic manifestations via somatic and genetic aberrations and recruitment of GBM stem-like cells (GSCs). Lysine specific demethylase 1 (LSD1), a flavin-containing oxidoreductase encoded by the KDM1A gene and containing the unique CoREST component, is an important histone-modifying enzyme belonging to the histone demethylase (KDM) subfamily and is responsible for master regulation of several signaling pathways in glioma cells. Pharmacological inhibition of LSD1, either individually or in a dual-targeted approach, is a logical strategy for the management of GBM. The current review discusses the role of LSD1 in various epigenetic modulations in differentiated glioma cells and GSCs. The 2D and 3D structural similarities/dissimilarities between LSD1 and MAOs have been analysed and presented along with a detailed discussion on different chemical classes of small molecule LSD1 inhibitors (both standalone and hybrid pharmacophores) that have shown promise in GBM chemotherapy.

Keywords: Glioblastoma multiforme, histone demethylases, Lysine-specific demethylase 1, LSD1 inhibitors, dual inhibitors, monoamine oxidase.

Graphical Abstract

[1]
Mucignat-Caretta, C. Tumors of the central nervous system: An update. Cancers, 2020, 12(2507), 1-4.
[http://dx.doi.org/10.3390/cancers12092507]
[2]
Hanif, F.; Muzaffar, K.; Perveen, K.; Malhi, S.M.; Simjee, S. Glioblastoma multiforme: A review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pac. J. Cancer Prev., 2017, 18(1), 3-9.
[http://dx.doi.org/10.22034/APJCP.2017.18.1.3] [PMID: 28239999]
[3]
Ostrom, Q.T.; Cioffi, G.; Gittleman, H.; Patil, N.; Waite, K.; Kruchko, C.; Barnholtz-Sloan, J.S. CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the united states in 2012-2016. Neuro-oncol., 2019, 21(Suppl. 5), v1-v100.
[http://dx.doi.org/10.1093/neuonc/noz150] [PMID: 31675094]
[4]
Tan, A.C.; Ashley, D.M.; López, G.Y.; Malinzak, M.; Friedman, H.S.; Khasraw, M. Management of glioblastoma: State of the art and fu-ture directions. CA Cancer J. Clin., 2020, 70(4), 299-312.
[http://dx.doi.org/10.3322/caac.21613] [PMID: 32478924]
[5]
Oliver, L.; Lalier, L.; Salaud, C.; Heymann, D.; Cartron, P.F.; Vallette, F.M. Drug resistance in glioblastoma: Are persisters the key to ther-apy? Cancer Drug Resist., 2020, 3, 287-301.
[http://dx.doi.org/10.20517/cdr.2020.29]
[6]
Chrysanthakopoulos, N.A.; Chrysanthakopoulos, P.A. Molecular biology and cellular signaling pathways in glioblastoma. Mathews J. Neurol., 2018, 3(1), 1-13.
[7]
Zheng, Y.C.; Ma, J.; Wang, Z.; Li, J.; Jiang, B.; Zhou, W.; Shi, X.; Wang, X.; Zhao, W.; Liu, H.M. A systematic review of histone lysine-specific demethylase 1 and its inhibitors. Med. Res. Rev., 2015, 35(5), 1032-1071.
[http://dx.doi.org/10.1002/med.21350] [PMID: 25990136]
[8]
Hyun, K.; Jeon, J.; Park, K.; Kim, J. Writing, erasing and reading histone lysine methylations. Exp. Mol. Med., 2017, 49(e324), 1-e324.
[http://dx.doi.org/10.1038/emm.2017.11]
[9]
Chen, Y.; Yang, Y.; Wang, F.; Wan, K.; Yamane, K.; Zhang, Y.; Lei, M. Crystal structure of human histone lysine-specific demethylase 1 (LSD1). Proc. Natl. Acad. Sci. USA, 2006, 103(38), 13956-13961.
[http://dx.doi.org/10.1073/pnas.0606381103] [PMID: 16956976]
[10]
Laurent, B.; Ruitu, L.; Murn, J.; Hempel, K.; Ferrao, R.; Xiang, Y.; Liu, S.; Garcia, B.A.; Wu, H.; Wu, F.; Steen, H.; Shi, Y. A specific LSD1/KDM1A isoform regulates neuronal differentiation through H3K9 demethylation. Mol. Cell, 2015, 57(6), 957-970.
[http://dx.doi.org/10.1016/j.molcel.2015.01.010] [PMID: 25684206]
[11]
Karytinos, A.; Forneris, F.; Profumo, A.; Ciossani, G.; Battaglioli, E.; Binda, C.; Mattevi, A. A novel mammalian flavin-dependent histone demethylase. J. Biol. Chem., 2009, 284(26), 17775-17782.
[http://dx.doi.org/10.1074/jbc.M109.003087] [PMID: 19407342]
[12]
Majello, B.; Gorini, F.; Saccà, C.D.; Amente, S. Expanding the role of the histone lysine-specific demethylase LSD1 in cancer. Cancers, 2019, 11, 1-324.
[http://dx.doi.org/10.3390/cancers11030324]
[13]
Amente, S.; Lania, L.; Majello, B. The histone LSD1 demethylase in stemness and cancer transcription programs. Biochim. Biophys. Acta, 2013, 1829(10), 981-986.
[http://dx.doi.org/10.1016/j.bbagrm.2013.05.002] [PMID: 23684752]
[14]
Gu, F.; Lin, Y.; Wang, Z.; Wu, X.; Ye, Z.; Wang, Y.; Lan, H. Biological roles of LSD1 beyond its demethylase activity. Cell. Mol. Life Sci., 2020, 77(17), 3341-3350.
[http://dx.doi.org/10.1007/s00018-020-03489-9] [PMID: 32193608]
[15]
Sehrawat, A.; Gao, L.; Wang, Y.; Bankhead, A., III; McWeeney, S.K.; King, C.J.; Schwartzman, J.; Urrutia, J.; Bisson, W.H.; Coleman, D.J.; Joshi, S.K.; Kim, D.H.; Sampson, D.A.; Weinmann, S.; Kallakury, B.V.S.; Berry, D.L.; Haque, R.; Van Den Eeden, S.K.; Sharma, S.; Bearss, J.; Beer, T.M.; Thomas, G.V.; Heiser, L.M.; Alumkal, J.J. LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc. Natl. Acad. Sci. USA, 2018, 115(18), E4179-E4188.
[http://dx.doi.org/10.1073/pnas.1719168115] [PMID: 29581250]
[16]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell, 2011, 144(5), 646-674.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[17]
Ismail, T.; Lee, H-K.; Kim, C.; Kwon, T.; Park, T.J.; Lee, H-S. KDM1A microenvironment, its oncogenic potential, and therapeutic signifi-cance. Epigenetics Chromatin, 2018, 11, 1-33.
[http://dx.doi.org/10.1186/s13072-018-0203-3]
[18]
Robertson, J.C.; Hurley, N.C.; Tortorici, M.; Ciossani, G.; Borrello, M.T.; Vellore, N.A.; Ganesan, A.; Mattevi, A.; Baron, R. Expanding the druggable space of the LSD1/CoREST epigenetic target: New potential binding regions for drug-like molecules, peptides, protein part-ners, and chromatin. PLOS Comput. Biol., 2013, 9(7), 1-e1003158.
[http://dx.doi.org/10.1371/journal.pcbi.1003158]
[19]
Forneris, F.; Binda, C.; Adamo, A.; Battaglioli, E.; Mattevi, A. Structural basis of LSD1-CoREST selectivity in histone H3 recognition. J. Biol. Chem., 2007, 282(28), 20070-20074.
[http://dx.doi.org/10.1074/jbc.C700100200] [PMID: 17537733]
[20]
Boulding, T.; McCuaig, R.D.; Tan, A.; Hardy, K.; Wu, F.; Dunn, J.; Kalimutho, M.; Sutton, C.R.; Forwood, J.K.; Bert, A.G.; Goodall, G.J.; Malik, L.; Yip, D.; Dahlstrom, J.E.; Zafar, A.; Khanna, K.K.; Rao, S. LSD1 activation promotes inducible EMT programs and modulates the tumour microenvironment in breast cancer. Sci. Rep., 2018, 8(1), 1-73.
[http://dx.doi.org/10.1038/s41598-017-17913-x]
[21]
Lv, T.; Yuan, D.; Miao, X.; Lv, Y.; Zhan, P.; Shen, X.; Song, Y. Over-expression of LSD1 promotes proliferation, migration and invasion in non-small cell lung cancer. PLoS One, 2012, 7(4), 1-e35065.
[http://dx.doi.org/10.1371/journal.pone.0035065]
[22]
Pilotto, S.; Speranzini, V.; Tortorici, M.; Durand, D.; Fish, A.; Valente, S.; Forneris, F.; Mai, A.; Sixma, T.K.; Vachette, P.; Mattevi, A. Interplay among nucleosomal DNA, histone tails, and corepressor CoREST underlies LSD1-mediated H3 demethylation. Proc. Natl. Acad. Sci. USA, 2015, 112(9), 2752-2757.
[http://dx.doi.org/10.1073/pnas.1419468112] [PMID: 25730864]
[23]
Metzger, E.; Wissmann, M.; Yin, N.; Müller, J.M.; Schneider, R.; Peters, A.H.; Günther, T.; Buettner, R.; Schüle, R. LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature, 2005, 437(7057), 436-439.
[http://dx.doi.org/10.1038/nature04020] [PMID: 16079795]
[24]
Toffolo, E.; Rusconi, F.; Paganini, L.; Tortorici, M.; Pilotto, S.; Heise, C.; Verpelli, C.; Tedeschi, G.; Maffioli, E.; Sala, C.; Mattevi, A.; Battaglioli, E. Phosphorylation of neuronal Lysine-Specific Demethylase 1LSD1/KDM1A impairs transcriptional repression by regulating interaction with CoREST and histone deacetylases HDAC1/2. J. Neurochem., 2014, 128(5), 603-616.
[http://dx.doi.org/10.1111/jnc.12457] [PMID: 24111946]
[25]
Hwang, I.; Cao, D.; Na, Y.; Kim, D.Y.; Zhang, T.; Yao, J.; Oh, H.; Hu, J.; Zheng, H.; Yao, Y.; Paik, J. Far upstream element-binding protein 1 Regulates LSD1 alternative splicing to promote terminal differentiation of neural progenitors. Stem Cell Reports, 2018, 10(4), 1208-1221.
[http://dx.doi.org/10.1016/j.stemcr.2018.02.013] [PMID: 29606613]
[26]
Wang, J.; Telese, F.; Tan, Y.; Li, W.; Jin, C.; He, X.; Basnet, H.; Ma, Q.; Merkurjev, D.; Zhu, X.; Liu, Z.; Zhang, J.; Ohgi, K.; Taylor, H.; White, R.R.; Tazearslan, C.; Suh, Y.; Macfarlan, T.S.; Pfaff, S.L.; Rosenfeld, M.G. LSD1n is an H4K20 demethylase regulating memory formation via transcriptional elongation control. Nat. Neurosci., 2015, 18(9), 1256-1264.
[http://dx.doi.org/10.1038/nn.4069] [PMID: 26214369]
[27]
Zorzan, M.; Giordan, E.; Redaelli, M.; Caretta, A.; Mucignat-Caretta, C. Molecular targets in glioblastoma. Future Oncol., 2015, 11(9), 1407-1420.
[http://dx.doi.org/10.2217/fon.15.22] [PMID: 25952786]
[28]
Shao, G.; Wang, J.; Li, Y.; Liu, X.; Xie, X.; Wan, X.; Yan, M.; Jin, J.; Lin, Q.; Zhu, H.; Zhang, L.; Gong, A.; Shao, Q.; Wu, C. Lysine-specific demethylase 1 mediates epidermal growth factor signaling to promote cell migration in ovarian cancer cells. Sci. Rep., 2015, 5, 1-15344.
[http://dx.doi.org/10.1038/srep15344]
[29]
Li, Z.; Bao, S.; Wu, Q.; Wang, H.; Eyler, C.; Sathornsumetee, S.; Shi, Q.; Cao, Y.; Lathia, J.; McLendon, R.E.; Hjelmeland, A.B.; Rich, J.N. Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell, 2009, 15(6), 501-513.
[http://dx.doi.org/10.1016/j.ccr.2009.03.018] [PMID: 19477429]
[30]
Banelli, B.; Carra, E.; Barbieri, F.; Würth, R.; Parodi, F.; Pattarozzi, A.; Carosio, R.; Forlani, A.; Allemanni, G.; Marubbi, D.; Florio, T.; Daga, A.; Romani, M. The histone demethylase KDM5A is a key factor for the resistance to temozolomide in glioblastoma. Cell Cycle, 2015, 14(21), 3418-3429.
[http://dx.doi.org/10.1080/15384101.2015.1090063] [PMID: 26566863]
[31]
Romani, M.; Daga, A.; Forlani, A.; Pistillo, M.P.; Banelli, B. Targeting of histone demethylases KDM5A and KDM6B inhibits the prolifera-tion of temozolomide-resistant glioblastoma cells. Cancers, 2019, 11, 1-878.
[http://dx.doi.org/10.3390/cancers11060878]
[32]
Yi, L.; Cui, Y.; Xu, Q.; Jiang, Y. Stabilization of LSD1 by deubiquitinating enzyme USP7 promotes glioblastoma cell tumorigenesis and metastasis through suppression of the p53 signaling pathway. Oncol. Rep., 2016, 36(5), 2935-2945.
[http://dx.doi.org/10.3892/or.2016.5099] [PMID: 27632941]
[33]
Tsai, M.C.; Manor, O.; Wan, Y.; Mosammaparast, N.; Wang, J.K.; Lan, F.; Shi, Y.; Segal, E.; Chang, H.Y. Long noncoding RNA as modu-lar scaffold of histone modification complexes. Science, 2010, 329(5992), 689-693.
[http://dx.doi.org/10.1126/science.1192002] [PMID: 20616235]
[34]
Bhan, A.; Mandal, S.S. LncRNA HOTAIR: A master regulator of chromatin dynamics and cancer. Biochim. Biophys. Acta, 2015, 1856(1), 151-164.
[http://dx.doi.org/10.1016/j.bbcan.2015.07.001] [PMID: 26208723]
[35]
Zhang, K.; Sun, X.; Zhou, X.; Han, L.; Chen, L.; Shi, Z.; Zhang, A.; Ye, M.; Wang, Q.; Liu, C.; Wei, J.; Ren, Y.; Yang, J.; Zhang, J.; Pu, P.; Li, M.; Kang, C. Long non-coding RNA HOTAIR promotes glioblastoma cell cycle progression in an EZH2 dependent manner. Oncotarget, 2015, 6(1), 537-546.
[http://dx.doi.org/10.18632/oncotarget.2681] [PMID: 25428914]
[36]
(a) Shi, J.; Lv, S.; Wu, M.; Wang, X.; Deng, Y.; Li, Y.; Li, K.; Zhao, H.; Zhu, X.; Ye, M. HOTAIR-EZH2 inhibitor AC1Q3QWB upregu-lates CWF19L1 and enhances cell cycle inhibition of CDK4/6 inhibitor palbociclib in glioma. Clin. Transl. Med., 2020, 10(1), 182-198.
[http://dx.doi.org/10.1002/ctm2.21] [PMID: 32508030]
(b) Zhao, J.; Jin, W.; Yi, K.; Wang, Q.; Zhou, J.; Tan, Y.; Xu, C.; Xiao, M.; Hong, B.; Xu, F.; Zhang, K.; Kang, C. Combination LSD1 and HOTAIR-EZH2 inhibition disrupts cell cycle processes and induces apoptosis in glioblastoma cells. Pharmacol. Res., 2021, 171, 105764.
[http://dx.doi.org/10.1016/j.phrs.2021.105764] [PMID: 34246782]
[37]
Gaweska, H.; Fitzpatrick, P.F. Structures and mechanism of the monoamine oxidase family. Biomol. Concepts, 2011, 2(5), 365-377.
[http://dx.doi.org/10.1515/BMC.2011.030] [PMID: 22022344]
[38]
Singh, M.M.; Johnson, B.; Venkatarayan, A.; Flores, E.R.; Zhang, J.; Su, X.; Barton, M.; Lang, F.; Chandra, J. Preclinical activity of com-bined HDAC and KDM1A inhibition in glioblastoma. Neuro-oncol., 2015, 17(11), 1463-1473.
[http://dx.doi.org/10.1093/neuonc/nov041] [PMID: 25795306]
[39]
Kategaya, L.; Di Lello, P.; Rougé, L.; Pastor, R.; Clark, K.R.; Drummond, J.; Kleinheinz, T.; Lin, E.; Upton, J.P.; Prakash, S.; Heideker, J.; McCleland, M.; Ritorto, M.S.; Alessi, D.R.; Trost, M.; Bainbridge, T.W.; Kwok, M.C.M.; Ma, T.P.; Stiffler, Z.; Brasher, B.; Tang, Y.; Jaishankar, P.; Hearn, B.R.; Renslo, A.R.; Arkin, M.R.; Cohen, F.; Yu, K.; Peale, F.; Gnad, F.; Chang, M.T.; Klijn, C.; Blackwood, E.; Mar-tin, S.E.; Forrest, W.F.; Ernst, J.A.; Ndubaku, C.; Wang, X.; Beresini, M.H.; Tsui, V.; Schwerdtfeger, C.; Blake, R.A.; Murray, J.; Maurer, T.; Wertz, I.E. USP7 small-molecule inhibitors interfere with ubiquitin binding. Nature, 2017, 550(7677), 534-538.
[http://dx.doi.org/10.1038/nature24006] [PMID: 29045385]
[40]
Wang, L.H.; Jiang, X.R.; Yang, J.Y.; Bao, X.F.; Chen, J.L.; Liu, X.; Chen, G.L.; Wu, C.F. SYP-5, a novel HIF-1 inhibitor, suppresses tumor cells invasion and angiogenesis. Eur. J. Pharmacol., 2016, 791, 560-568.
[http://dx.doi.org/10.1016/j.ejphar.2016.09.027] [PMID: 27664769]
[41]
Maes, T.; Mascaró, C.; Rotllant, D.; Lufino, M.; Estiarte, A.; Guibourt, N.; Cavalcanti, F.; Griñan-Ferré, C.; Pallàs, M.; Nadal, R.; Armario, A.; Ferrer, I.; Ortega, A.; Valls, N.; Fyfe, M.; Martinell, M.; Castro, P.J.C.; Buesa, A.C. Modulation of KDM1A with vafidemstat rescues memory deficit and behavioral alterations. PLoS One, 2020, 15(5), e0233468.
[http://dx.doi.org/10.1371/journal.pone.0233468]
[42]
Schmitt, M.L.; Hauser, A.T.; Carlino, L.; Pippel, M.; Schulz-Fincke, J.; Metzger, E.; Willmann, D.; Yiu, T.; Barton, M.; Schüle, R.; Sippl, W.; Jung, M. Nonpeptidic propargylamines as inhibitors of lysine specific demethylase 1 (LSD1) with cellular activity. J. Med. Chem., 2013, 56(18), 7334-7342.
[http://dx.doi.org/10.1021/jm400792m] [PMID: 24007511]
[43]
Prusevich, P.; Kalin, J.H.; Ming, S.A.; Basso, M.; Givens, J.; Li, X.; Hu, J.; Taylor, M.S.; Cieniewicz, A.M.; Hsiao, P.Y.; Huang, R.; Rob-erson, H.; Adejola, N.; Avery, L.B.; Casero, R.A., Jr; Taverna, S.D.; Qian, J.; Tackett, A.J.; Ratan, R.R.; McDonald, O.G.; Feinberg, A.P.; Cole, P.A. A selective phenelzine analogue inhibitor of histone demethylase LSD1. ACS Chem. Biol., 2014, 9(6), 1284-1293.
[http://dx.doi.org/10.1021/cb500018s] [PMID: 24707965]
[44]
Xi, J.; Xu, S.; Zhang, L.; Bi, X.; Ren, Y.; Liu, Y.C.; Gu, Y.; Xu, Y.; Lan, F.; Zha, X. Design, synthesis and biological activity of 4-(4-benzyloxy)phenoxypiperidines as selective and reversible LSD1 inhibitors. Bioorg. Chem., 2018, 78, 7-16.
[http://dx.doi.org/10.1016/j.bioorg.2018.02.016] [PMID: 29524666]
[45]
Hitchin, J.R.; Blagg, J.; Burke, R.; Burns, S.; Cockerill, M.J.; Fairweather, E.E.; Hutton, C.; Jordan, A.M.; McAndrew, C.; Mirza, A.; Mould, D.; Thomson, G.J.; Waddella, I.; Ogilvie, D.J. Development and evaluation of selective, reversible LSD1 inhibitors derived from frag-ments. MedChemComm, 2013, 4(11), 1513-1522.
[http://dx.doi.org/10.1039/c3md00226h]
[46]
Ma, Q.S.; Yao, Y.; Zheng, Y.C.; Feng, S.; Chang, J.; Yu, B.; Liu, H.M. Ligand-based design, synthesis and biological evaluation of xan-thine derivatives as LSD1/KDM1A inhibitors. Eur. J. Med. Chem., 2019, 162, 555-567.
[http://dx.doi.org/10.1016/j.ejmech.2018.11.035] [PMID: 30472603]
[47]
Xu, S.; Zhou, C.; Liu, R.; Zhu, Q.; Xu, Y.; Lan, F.; Zha, X. Optimization of 5-arylidene barbiturates as potent, selective, reversible LSD1 inhibitors for the treatment of acute promyelocytic leukemia. Bioorg. Med. Chem., 2018, 26(17), 4871-4880.
[http://dx.doi.org/10.1016/j.bmc.2018.08.026] [PMID: 30153955]
[48]
Zhou, C.; Kang, D.; Xu, Y.; Zhang, L.; Zha, X. Identification of novel selective lysine-specific demethylase 1 (LSD1) inhibitors using a pharmacophore-based virtual screening combined with docking. Chem. Biol. Drug Des., 2015, 85(6), 659-671.
[http://dx.doi.org/10.1111/cbdd.12461] [PMID: 25346381]
[49]
Singh, M.M.; Manton, C.A.; Bhat, K.P.; Tsai, W.W.; Aldape, K.; Barton, M.C.; Chandra, J. Inhibition of LSD1 sensitizes glioblastoma cells to histone deacetylase inhibitors. Neuro-oncol., 2011, 13(8), 894-903.
[http://dx.doi.org/10.1093/neuonc/nor049] [PMID: 21653597]
[50]
Sareddy, G.R.; Nair, B.C.; Krishnan, S.K.; Gonugunta, V.K.; Zhang, Q.G.; Suzuki, T.; Miyata, N.; Brenner, A.J.; Brann, D.W.; Vadlamudi, R.K. KDM1 is a novel therapeutic target for the treatment of gliomas. Oncotarget, 2013, 4(1), 18-28.
[http://dx.doi.org/10.18632/oncotarget.725] [PMID: 23248157]
[51]
Saccà, C.D.; Gorini, F.; Ambrosio, S.; Amente, S.; Faicchia, D.; Matarese, G.; Lania, L.; Majello, B. Inhibition of lysine-specific demethyl-ase LSD1 induces senescence in Glioblastoma cells through a HIF-1α-dependent pathway. Biochim. Biophys. Acta. Gene Regul. Mech., 2019, 1862(5), 535-546.
[http://dx.doi.org/10.1016/j.bbagrm.2019.03.004] [PMID: 30951900]
[52]
Alves, A.L.V.; Gomes, I.N.F.; Carloni, A.C.; Rosa, M.N.; da Silva, L.S.; Evangelista, A.F.; Reis, R.M.; Silva, V.A.O. Role of glioblastoma stem cells in cancer therapeutic resistance: A perspective on antineoplastic agents from natural sources and chemical derivatives. Stem Cell Res. Ther., 2021, 12, 1-206.
[http://dx.doi.org/10.1186/s13287-021-02231-x]
[53]
Prager, B.C.; Bhargava, S.; Mahadev, V.; Hubert, C.G.; Rich, J.N. Glioblastoma stem cells: Driving resilience through chaos. Trends Cancer, 2020, 6(3), 223-235.
[http://dx.doi.org/10.1016/j.trecan.2020.01.009] [PMID: 32101725]
[54]
Suvà, M.L.; Rheinbay, E.; Gillespie, S.M.; Patel, A.P.; Wakimoto, H.; Rabkin, S.D.; Riggi, N.; Chi, A.S.; Cahill, D.P.; Nahed, B.V.; Curry, W.T.; Martuza, R.L.; Rivera, M.N.; Rossetti, N.; Kasif, S.; Beik, S.; Kadri, S.; Tirosh, I.; Wortman, I.; Shalek, A.K.; Rozenblatt-Rosen, O.; Regev, A.; Louis, D.N.; Bernstein, B.E. Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells. Cell, 2014, 157(3), 580-594.
[http://dx.doi.org/10.1016/j.cell.2014.02.030] [PMID: 24726434]
[55]
Kozono, D.; Li, J.; Nitta, M.; Sampetrean, O.; Gonda, D.; Kushwaha, D.S.; Merzon, D.; Ramakrishnan, V.; Zhu, S.; Zhu, K.; Matsui, H.; Harismendy, O.; Hua, W.; Mao, Y.; Kwon, C.H.; Saya, H.; Nakano, I.; Pizzo, D.P.; VandenBerg, S.R.; Chen, C.C. Dynamic epigenetic regu-lation of glioblastoma tumorigenicity through LSD1 modulation of MYC expression. Proc. Natl. Acad. Sci. USA, 2015, 112(30), E4055-E4064.
[http://dx.doi.org/10.1073/pnas.1501967112] [PMID: 26159421]
[56]
Hiramatsu, H.; Kobayashi, K.; Kobayashi, K.; Haraguchi, T.; Ino, Y.; Todo, T.; Iba, H. The role of the SWI/SNF chromatin remodeling complex in maintaining the stemness of glioma initiating cells. Sci. Rep., 2017, 7(1), 1-889.
[http://dx.doi.org/10.1038/s41598-017-00982-3]
[57]
Zhou, A.; Lin, K.; Zhang, S.; Chen, Y.; Zhang, N.; Xue, J.; Wang, Z.; Aldape, K.D.; Xie, K.; Woodgett, J.R.; Huang, S. Nuclear GSK3β promotes tumorigenesis by phosphorylating KDM1A and inducing its deubiquitylation by USP22. Nat. Cell Biol., 2016, 18(9), 954-966.
[http://dx.doi.org/10.1038/ncb3396] [PMID: 27501329]
[58]
Singh, S.K.; Hawkins, C.; Clarke, I.D.; Squire, J.A.; Bayani, J.; Hide, T.; Henkelman, R.M.; Cusimano, M.D.; Dirks, P.B. Identification of human brain tumour initiating cells. Nature, 2004, 432(7015), 396-401.
[http://dx.doi.org/10.1038/nature03128] [PMID: 15549107]
[59]
Dai, X.J.; Liu, Y.; Xue, L.P.; Xiong, X.P.; Zhou, Y.; Zheng, Y.C.; Liu, H.M. Reversible lysine specific demethylase 1 (LSD1) inhibitors: A promising wrench to impair LSD1. J. Med. Chem., 2021, 64(5), 2466-2488.
[http://dx.doi.org/10.1021/acs.jmedchem.0c02176] [PMID: 33619958]
[60]
Fu, X.; Zhang, P.; Yu, B. Advances toward LSD1 inhibitors for cancer therapy. Future Med. Chem., 2017, 9(11), 1227-1242.
[http://dx.doi.org/10.4155/fmc-2017-0068] [PMID: 28722477]
[61]
Fang, Y.; Yang, C.; Yu, Z.; Li, X.; Mu, Q.; Liao, G.; Yu, B. Natural products as LSD1 inhibitors for cancer therapy. Acta Pharm. Sin. B, 2020, 11(3), 621-631.
[http://dx.doi.org/10.1016/j.apsb.2020.06.007] [PMID: 32837872]
[62]
Stazi, G.; Zwergel, C.; Valente, S.; Mai, A. LSD1 inhibitors: A patent review (2010-2015). Expert Opin. Ther. Pat., 2016, 26(5), 565-580.
[http://dx.doi.org/10.1517/13543776.2016.1165209] [PMID: 27019002]
[63]
Mould, D.P.; Bremberg, U.; Jordan, A.M.; Geitmann, M.; Maiques-Diaz, A.; McGonagle, A.E.; Small, H.F.; Somervaille, T.C.P.; Ogilvie, D. Development of 5-hydroxypyrazole derivatives as reversible inhibitors of lysine specific demethylase 1. Bioorg. Med. Chem. Lett., 2017, 27(14), 3190-3195.
[http://dx.doi.org/10.1016/j.bmcl.2017.05.018] [PMID: 28545974]
[64]
Sharma, S.K.; Wu, Y.; Steinbergs, N.; Crowley, M.L.; Hanson, A.S.; Casero, R.A., Jr; Woster, P.M. (Bis)urea and (bis)thiourea inhibitors of lysine-specific demethylase 1 as epigenetic modulators. J. Med. Chem., 2010, 53(14), 5197-5212.
[http://dx.doi.org/10.1021/jm100217a] [PMID: 20568780]
[65]
Ma, L.Y.; Zheng, Y.C.; Wang, S.Q.; Wang, B.; Wang, Z.R.; Pang, L.P.; Zhang, M.; Wang, J.W.; Ding, L.; Li, J.; Wang, C.; Hu, B.; Liu, Y.; Zhang, X.D.; Wang, J.J.; Wang, Z.J.; Zhao, W.; Liu, H.M. Design, synthesis, and structure-activity relationship of novel LSD1 inhibitors based on pyrimidine-thiourea hybrids as potent, orally active antitumor agents. J. Med. Chem., 2015, 58(4), 1705-1716.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00037] [PMID: 25610955]
[66]
Sharma, S.; Sorna, V.; Vankayalapati, H. Substituted-1Hbenzo[ d]imidazole series compounds as lysine-specific demethylase 1 (LSD1) inhibitors. U.S. Patent 2015031564 (A2), 2015.
[67]
Sorna, V.; Theisen, E.R.; Stephens, B.; Warner, S.L.; Bearss, D.J.; Vankayalapati, H.; Sharma, S. High-throughput virtual screening identi-fies novel N′-(1-phenylethylidene)-benzohydrazides as potent, specific, and reversible LSD1 inhibitors. J. Med. Chem., 2013, 56(23), 9496-9508.
[http://dx.doi.org/10.1021/jm400870h] [PMID: 24237195]
[68]
Kanouni, T.; Severin, C.; Cho, R.W.; Yuen, N.Y.; Xu, J.; Shi, L.; Lai, C.; Del Rosario, J.R.; Stansfield, R.K.; Lawton, L.N.; Hosfield, D.; O’Connell, S.; Kreilein, M.M.; Tavares-Greco, P.; Nie, Z.; Kaldor, S.W.; Veal, J.M.; Stafford, J.A.; Chen, Y.K. Discovery of CC-90011: A potent and selective reversible inhibitor of lysine specific demethylase 1 (LSD1). J. Med. Chem., 2020, 63(23), 14522-14529.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00978] [PMID: 33034194]
[69]
Hazeldine, S.; Pachaiyappan, B.; Steinbergs, N.; Nowotarski, S.; Hanson, A.S.; Casero, R.A., Jr; Woster, P.M. Low molecular weight ami-doximes that act as potent inhibitors of lysine-specific demethylase 1. J. Med. Chem., 2012, 55(17), 7378-7391.
[http://dx.doi.org/10.1021/jm3002845] [PMID: 22876979]
[70]
Zheng, Y.C.; Duan, Y.C.; Ma, J.L.; Xu, R.M.; Zi, X.; Lv, W.L.; Wang, M.M.; Ye, X.W.; Zhu, S.; Mobley, D.; Zhu, Y.Y.; Wang, J.W.; Li, J.F.; Wang, Z.R.; Zhao, W.; Liu, H.M. Triazole-dithiocarbamate based selective lysine specific demethylase 1 (LSD1) inactivators inhibit gastric cancer cell growth, invasion, and migration. J. Med. Chem., 2013, 56(21), 8543-8560.
[http://dx.doi.org/10.1021/jm401002r] [PMID: 24131029]
[71]
Sartori, L.; Mercurio, C.; Amigoni, F.; Cappa, A.; Fagá, G.; Fattori, R.; Legnaghi, E.; Ciossani, G.; Mattevi, A.; Meroni, G.; Moretti, L.; Cecatiello, V.; Pasqualato, S.; Romussi, A.; Thaler, F.; Trifiró, P.; Villa, M.; Vultaggio, S.; Botrugno, O.A.; Dessanti, P.; Minucci, S.; Zagarrí, E.; Carettoni, D.; Iuzzolino, L.; Varasi, M.; Vianello, P. Thieno[3,2-b]pyrrole-5-carboxamides as new reversible inhibitors of his-tone lysine demethylase KDM1A/LSD1. Part 1: High-throughput screening and preliminary exploration. J. Med. Chem., 2017, 60(5), 1673-1692.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01018] [PMID: 28186755]
[72]
Abdel-Magid, A.F. Lysine-Specific Demethylase 1 (LSD1) inhibitors as potential treatment for different types of cancers. ACS Med. Chem. Lett., 2017, 8(11), 1134-1135.
[http://dx.doi.org/10.1021/acsmedchemlett.7b00426] [PMID: 29152043]
[73]
Ma, L.; Wang, H.; You, Y.; Ma, C.; Liu, Y.; Yang, F.; Zheng, Y.; Liu, H. Exploration of 5-cyano-6-phenylpyrimidin derivatives containing an 1,2,3-triazole moiety as potent FAD-based LSD1 inhibitors. Acta Pharm. Sin. B, 2020, 10(9), 1658-1668.
[http://dx.doi.org/10.1016/j.apsb.2020.02.006] [PMID: 33088686]
[74]
Dulla, B.; Kirla, K.T.; Rathore, V.; Deora, G.S.; Kavela, S.; Maddika, S.; Chatti, K.; Reiser, O.; Iqbal, J.; Pal, M. Synthesis and evaluation of 3-amino/guanidine substituted phenyl oxazoles as a novel class of LSD1 inhibitors with anti-proliferative properties. Org. Biomol. Chem., 2013, 11(19), 3103-3107.
[http://dx.doi.org/10.1039/c3ob40217g] [PMID: 23575971]
[75]
Wang, J.; Lu, F.; Ren, Q.; Sun, H.; Xu, Z.; Lan, R.; Liu, Y.; Ward, D.; Quan, J.; Ye, T.; Zhang, H. Novel histone demethylase LSD1 inhibi-tors selectively target cancer cells with pluripotent stem cell properties. Cancer Res., 2011, 71(23), 7238-7249.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-0896] [PMID: 21975933]
[76]
Wang, S.; Zhao, L.J.; Zheng, Y.C.; Shen, D.D.; Miao, E.F.; Qiao, X.P.; Zhao, L.J.; Liu, Y.; Huang, R.; Yu, B.; Liu, H.M. Design, synthesis and biological evaluation of [1,2,4]triazolo[1,5-a]pyrimidines as potent lysine specific demethylase 1 (LSD1/KDM1A) inhibitors. Eur. J. Med. Chem., 2017, 125(5), 940-951.
[http://dx.doi.org/10.1016/j.ejmech.2016.10.021] [PMID: 27769034]
[77]
Wang, X.; Zhang, C.; Zhang, X.; Yan, J.; Wang, J.; Jiang, Q.; Zhao, L.; Zhao, D.; Cheng, M. Design, synthesis and biological evaluation of tetrahydroquinoline-based reversible LSD1 inhibitors. Eur. J. Med. Chem., 2020, 194, 1-112243.
[http://dx.doi.org/10.1016/j.ejmech.2020.112243]
[78]
Li, L.; Li, R.; Wang, Y. Identification of selective and reversible LSD1 inhibitors with anti-metastasis activity by high-throughput docking. Bioorg. Med. Chem. Lett., 2019, 29(4), 544-548.
[http://dx.doi.org/10.1016/j.bmcl.2018.12.067] [PMID: 30611617]
[79]
He, X.; Gao, Y.; Hui, Z.; Shen, G.; Wang, S.; Xie, T.; Ye, X.Y. 4-Hydroxy-3-methylbenzofuran-2-carbohydrazones as novel LSD1 inhibi-tors. Bioorg. Med. Chem. Lett., 2020, 30, 1-127109.
[http://dx.doi.org/10.1016/j.bmcl.2020.127109]
[80]
Liu, H.M.; Suo, F.Z.; Li, X.B.; You, Y.H.; Lv, C.T.; Zheng, C.X.; Zhang, G.C.; Liu, Y.J.; Kang, W.T.; Zheng, Y.C.; Xu, H.W. Discovery and synthesis of novel indole derivatives-containing 3-methylenedihydrofuran-2(3H)-one as irreversible LSD1 inhibitors. Eur. J. Med. Chem., 2019, 175, 357-372.
[http://dx.doi.org/10.1016/j.ejmech.2019.04.065] [PMID: 31096156]
[81]
Alnabulsi, S.; Al-Hurani, E.A.; Al-Shar’i, N.A.; El-Elimat, T. Amino-carboxamide benzothiazoles as potential LSD1 hit inhibitors. J. Mol. Graph. Model., 2019, 93, 1-107440.
[http://dx.doi.org/10.1016/j.jmgm.2019.107440]
[82]
Speranzini, V.; Rotili, D.; Ciossani, G.; Pilotto, S.; Marrocco, B.; Forgione, M.; Lucidi, A.; Forneris, F.; Mehdipour, P.; Velankar, S.; Mai, A.; Mattevi, A. Polymyxins and quinazolines are LSD1/KDM1A inhibitors with unusual structural features. Sci. Adv., 2016, 2, 1-e1601017.
[http://dx.doi.org/10.1126/sciadv.1601017]
[83]
Clinical Trials: Studies found for: LSD1. Available from: https://clinicaltrials.gov/ct2/results?cond=&term=LSD1&cntry=&state=&city=&dist= (Accessed June 5, 2021).
[84]
Fang, Y.; Liao, G.; Yu, B. LSD1/KDM1A inhibitors in clinical trials: Advances and prospects. J. Hematol. Oncol., 2019, 12, 1-129.
[http://dx.doi.org/10.1186/s13045-019-0811-9]
[85]
Dai, X.J.; Liu, Y.; Xiong, X.P.; Xue, L.P.; Zheng, Y.C.; Liu, H.M. Tranylcypromine based lysine-specific demethylase 1 inhibitor: Sum-mary and perspective. J. Med. Chem., 2020, 63(23), 14197-14215.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00919] [PMID: 32931269]
[86]
Wang, X.; Huang, B.; Suzuki, T.; Liu, X.; Zhan, P. Medicinal chemistry insights in the discovery of novel LSD1 inhibitors. Epigenomics, 2015, 7(8), 1379-1396.
[http://dx.doi.org/10.2217/epi.15.86] [PMID: 26646727]
[87]
Yang, M.; Culhane, J.C.; Szewczuk, L.M.; Jalili, P.; Ball, H.L.; Machius, M.; Cole, P.A.; Yu, H. Structural basis for the inhibition of the LSD1 histone demethylase by the antidepressant trans-2-phenylcyclopropylamine. Biochemistry, 2007, 46(27), 8058-8065.
[http://dx.doi.org/10.1021/bi700664y] [PMID: 17569509]
[88]
Binda, C.; Li, M.; Hubalek, F.; Restelli, N.; Edmondson, D.E.; Mattevi, A. Insights into the mode of inhibition of human mitochondrial monoamine oxidase B from high-resolution crystal structures. Proc. Natl. Acad. Sci. USA, 2003, 100(17), 9750-9755.
[http://dx.doi.org/10.1073/pnas.1633804100] [PMID: 12913124]
[89]
Cai, C.; He, H.H.; Gao, S.; Chen, S.; Yu, Z.; Gao, Y.; Chen, S.; Chen, M.W.; Zhang, J.; Ahmed, M.; Wang, Y.; Metzger, E.; Schüle, R.; Liu, X.S.; Brown, M.; Balk, S.P. Lysine-specific demethylase 1 has dual functions as a major regulator of androgen receptor transcriptional ac-tivity. Cell Rep., 2014, 9(5), 1618-1627.
[http://dx.doi.org/10.1016/j.celrep.2014.11.008] [PMID: 25482560]
[90]
Zhang, L.; Zhang, J.; Jiang, Q.; Zhang, L.; Song, W. Zinc binding groups for histone deacetylase inhibitors. J. Enzyme Inhib. Med. Chem., 2018, 33(1), 714-721.
[http://dx.doi.org/10.1080/14756366.2017.1417274] [PMID: 29616828]
[91]
Duan, Y.C.; Ma, Y.C.; Qin, W.P.; Ding, L.N.; Zheng, Y.C.; Zhu, Y.L.; Zhai, X.Y.; Yang, J.; Ma, C.Y.; Guan, Y.Y. Design and synthesis of tranylcypromine derivatives as novel LSD1/HDACs dual inhibitors for cancer treatment. Eur. J. Med. Chem., 2017, 140, 392-402.
[http://dx.doi.org/10.1016/j.ejmech.2017.09.038] [PMID: 28987602]
[92]
Milelli, A.; Marchetti, C.; Turrini, E.; Catanzaro, E.; Mazzone, R.; Tomaselli, D.; Fimognari, C.; Tumiatti, V.; Minarini, A. Novel polyam-ine-based histone deacetylases-lysine demethylase 1 dual binding inhibitors. Bioorg. Med. Chem. Lett., 2018, 28(6), 1001-1004.
[http://dx.doi.org/10.1016/j.bmcl.2018.02.034] [PMID: 29496367]
[93]
Kalin, J.H.; Wu, M.; Gomez, A.V.; Song, Y.; Das, J.; Hayward, D.; Adejola, N.; Wu, M.; Panova, I.; Chung, H.J.; Kim, E.; Roberts, H.J.; Roberts, J.M.; Prusevich, P.; Jeliazkov, J.R.; Roy, B.S.S.; Fairall, L.; Milano, C.; Eroglu, A.; Proby, C.M.; Dinkova-Kostova, A.T.; Han-cock, W.W.; Gray, J.J.; Bradner, J.E.; Valente, S.; Mai, A.; Anders, N.M.; Rudek, M.A.; Hu, Y.; Ryu, B.; Schwabe, J.W.R.; Mattevi, A.; Alani, R.M.; Cole, P.A. Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors. Nat. Commun., 2018, 9(1), 1-53.
[http://dx.doi.org/10.1038/s41467-017-02242-4]
[94]
Sadhu, M.N.; Sivanandhan, D.; Gajendran, C.; Tantry, S.; Dewang, P.; Murugan, K.; Chickamunivenkatappa, S.; Zainuddin, M.; Nair, S.; Vaithilingam, K.; Rajagopal, S. Novel dual LSD1/HDAC6 inhibitors for the treatment of multiple myeloma. Bioorg. Med. Chem. Lett., 2021, 34, 1-127763.
[http://dx.doi.org/10.1016/j.bmcl.2020.127763]
[95]
Inui, K.; Zhao, Z.; Yuan, J.; Jayaprakash, S.; Le, L.T.M.; Drakulic, S.; Sander, B.; Golas, M.M. Stepwise assembly of functional C-terminal REST/NRSF transcriptional repressor complexes as a drug target. Protein Sci., 2017, 26(5), 997-1011.
[http://dx.doi.org/10.1002/pro.3142] [PMID: 28218430]
[96]
Duan, Y.C.; Jin, L.F.; Ren, H.M.; Zhang, S.J.; Liu, Y.J.; Xu, Y.T.; He, Z.H.; Song, Y.; Yuan, H.; Chen, S.H.; Guan, Y.Y. Design, synthesis, and biological evaluation of novel dual inhibitors targeting lysine specific demethylase 1 (LSD1) and histone deacetylases (HDAC) for treatment of gastric cancer. Eur. J. Med. Chem., 2021, 220, 1-113453.
[http://dx.doi.org/10.1016/j.ejmech.2021.113453]
[97]
Holshouser, S.; Dunworth, M.; Murray-Stewart, T.; Peterson, Y.K.; Burger, P.; Kirkpatrick, J.; Chen, H.H.; Casero, R.A., Jr; Woster, P.M. Dual inhibitors of LSD1 and spermine oxidase. MedChemComm, 2019, 10(5), 778-790.
[http://dx.doi.org/10.1039/C8MD00610E] [PMID: 31191868]
[98]
Li, Z.R.; Suo, F.Z.; Hu, B.; Guo, Y.J.; Fu, D.J.; Yu, B.; Zheng, Y.C.; Liu, H.M. Identification of osimertinib (AZD9291) as a lysine specific demethylase 1 inhibitor. Bioorg. Chem., 2019, 84, 164-169.
[http://dx.doi.org/10.1016/j.bioorg.2018.11.018] [PMID: 30502627]
[99]
Arvanitis, C.D.; Ferraro, G.B.; Jain, R.K. The blood-brain barrier and blood-tumour barrier in brain tumours and metastases. Nat. Rev. Cancer, 2020, 20(1), 26-41.
[http://dx.doi.org/10.1038/s41568-019-0205-x] [PMID: 31601988]
[100]
de Trizio, I.; Errede, M.; d’Amati, A.; Girolamo, F.; Virgintino, D. Expression of P-gp in Glioblastoma: What we can learn from brain development. Curr. Pharm. Des., 2020, 26(13), 1428-1437.
[http://dx.doi.org/10.2174/1381612826666200318130625] [PMID: 32186270]
[101]
Bleau, A.M.; Huse, J.T.; Holland, E.C. The ABCG2 resistance network of glioblastoma. Cell Cycle, 2009, 8(18), 2936-2944.
[http://dx.doi.org/10.4161/cc.8.18.9504] [PMID: 19713741]
[102]
Luo, H.; Shusta, E.V. Blood–brain barrier modulation to improve glioma drug delivery. Pharmaceutics, 2020, 12, 1-1085.
[http://dx.doi.org/10.3390/pharmaceutics12111085]
[103]
Kim, S.A.; Zhu, J.; Yennawar, N.; Eek, P.; Tan, S. Crystal structure of the LSD1/CoREST histone demethylase bound to its nucleosome substrate. Mol. Cell, 2020, 78(5), 903-914.e4.
[http://dx.doi.org/10.1016/j.molcel.2020.04.019] [PMID: 32396821]
[104]
Mimasu, S.; Sengoku, T.; Fukuzawa, S.; Umehara, T.; Yokoyama, S. Crystal structure of histone demethylase LSD1 and tranylcypromine at 2.25 Å. Biochem. Biophys. Res. Commun., 2008, 366(1), 15-22.
[http://dx.doi.org/10.1016/j.bbrc.2007.11.066] [PMID: 18039463]
[105]
Pilotto, S.; Speranzini, V.; Marabelli, C.; Rusconi, F.; Toffolo, E.; Grillo, B.; Battaglioli, E.; Mattevi, A. LSD1/KDM1A mutations associat-ed to a newly described form of intellectual disability impair demethylase activity and binding to transcription factors. Hum. Mol. Genet., 2016, 25(12), 2578-2587.
[http://dx.doi.org/10.1093/hmg/ddw120] [PMID: 27094131]
[106]
De Colibus, L.; Li, M.; Binda, C.; Lustig, A.; Edmondson, D.E.; Mattevi, A. Three-dimensional structure of human monoamine oxidase A (MAO A): Relation to the structures of rat MAO A and human MAO B. Proc. Natl. Acad. Sci. USA, 2005, 102(36), 12684-12689.
[http://dx.doi.org/10.1073/pnas.0505975102] [PMID: 16129825]
[107]
Ogasawara, D.; Itoh, Y.; Tsumoto, H.; Kakizawa, T.; Mino, K.; Fukuhara, K.; Nakagawa, H.; Hasegawa, M.; Sasaki, R.; Mizukami, T.; Miyata, N.; Suzuki, T. Lysine-specific demethylase 1-selective inactivators: Protein-targeted drug delivery mechanism. Angew. Chem. Int. Ed. Engl., 2013, 52(33), 8620-8624.
[http://dx.doi.org/10.1002/anie.201303999] [PMID: 23824985]
[108]
Binda, C.; Mattevi, A.; Edmondson, D.E. Structure-function relationships in flavoenzyme-dependent amine oxidations: A comparison of polyamine oxidase and monoamine oxidase. J. Biol. Chem., 2002, 277(27), 23973-23976.
[http://dx.doi.org/10.1074/jbc.R200005200] [PMID: 12015330]
[109]
Li, M.; Binda, C.; Mattevi, A.; Edmondson, D.E. Functional role of the “aromatic cage” in human monoamine oxidase B: Structures and catalytic properties of Tyr435 mutant proteins. Biochemistry, 2006, 45(15), 4775-4784.
[http://dx.doi.org/10.1021/bi051847g] [PMID: 16605246]
[110]
Kumar, B.; Gupta, V.P.; Kumar, V. A perspective on monoamine oxidase enzyme as drug target: Challenges and opportunities. Curr. Drug Targets, 2017, 18(1), 87-97.
[http://dx.doi.org/10.2174/1389450117666151209123402] [PMID: 26648064]
[111]
Schmidt, D.M.; McCafferty, D.G. trans-2-Phenylcyclopropylamine is a mechanism-based inactivator of the histone demethylase LSD1. Biochemistry, 2007, 46(14), 4408-4416.
[http://dx.doi.org/10.1021/bi0618621] [PMID: 17367163]
[112]
Welch, D.; Kahen, E.; Fridley, B.; Brohl, A.S.; Cubitt, C.L.; Reed, D.R. Small molecule inhibition of lysine-specific demethylase 1 (LSD1) and histone deacetylase (HDAC) alone and in combination in Ewing sarcoma cell lines. PLoS One, 2019, 14(9), 1-e0222228.
[http://dx.doi.org/10.1371/journal.pone.0222228]
[113]
Mimasu, S.; Umezawa, N.; Sato, S.; Higuchi, T.; Umehara, T.; Yokoyama, S. Structurally designed trans-2-phenylcyclopropylamine deriv-atives potently inhibit histone demethylase LSD1/KDM1. Biochemistry, 2010, 49(30), 6494-6503.
[http://dx.doi.org/10.1021/bi100299r] [PMID: 20568732]
[114]
Kondo, Y.; Umehara, T. Potent Inhibitor of LSD1 as a treatment of glioblastoma. Available from: https://www.nypharmaforum.org/wp-content/uploads/2017/12/NYPF_SUM_Riken_Umehara_Final.pdf
[115]
Niwa, H.; Sato, S.; Handa, N.; Sengoku, T.; Umehara, T.; Yokoyama, S. Development and structural evaluation of N-alkylated trans-2-phenylcyclopropylamine-based LSD1 inhibitors. ChemMedChem, 2020, 15(9), 787-793.
[http://dx.doi.org/10.1002/cmdc.202000014] [PMID: 32166890]
[116]
Saito, S.; Kikuchi, J.; Koyama, D.; Sato, S.; Koyama, H.; Osada, N.; Kuroda, Y.; Akahane, K.; Inukai, T.; Umehara, T.; Furukawa, Y. Eradication of central nervous system leukemia of T-Cell origin with a brain-permeable LSD1 inhibitor. Clin. Cancer Res., 2019, 25(5), 1601-1611.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-0919] [PMID: 30518632]
[117]
Neelamegam, R.; Ricq, E.L.; Malvaez, M.; Patnaik, D.; Norton, S.; Carlin, S.M.; Hill, I.T.; Wood, M.A.; Haggarty, S.J.; Hooker, J.M. Brain-penetrant LSD1 inhibitors can block memory consolidation. ACS Chem. Neurosci., 2012, 3(2), 120-128.
[http://dx.doi.org/10.1021/cn200104y] [PMID: 22754608]
[118]
Bailey, C.P.; Figueroa, M.; Gangadharan, A.; Yang, Y.; Romero, M.M.; Kennis, B.A.; Yadavilli, S.; Henry, V.; Collier, T.; Monje, M.; Lee, D.A.; Wang, L.; Nazarian, J.; Gopalakrishnan, V.; Zaky, W.; Becher, O.J.; Chandra, J. Pharmacologic inhibition of lysine-specific deme-thylase 1 as a therapeutic and immune-sensitization strategy in pediatric high-grade glioma. Neuro-oncol., 2020, 22(9), 1302-1314.
[http://dx.doi.org/10.1093/neuonc/noaa058] [PMID: 32166329]
[119]
Sareddy, G.R.; Viswanadhapalli, S.; Surapaneni, P.; Suzuki, T.; Brenner, A.; Vadlamudi, R.K. Novel KDM1A inhibitors induce differentia-tion and apoptosis of glioma stem cells via unfolded protein response pathway. Oncogene, 2017, 36(17), 2423-2434.
[http://dx.doi.org/10.1038/onc.2016.395] [PMID: 27893719]
[120]
Ogasawara, D.; Suzuki, T.; Mino, K.; Ueda, R.; Khan, M.N.; Matsubara, T.; Koseki, K.; Hasegawa, M.; Sasaki, R.; Nakagawa, H.; Mizuka-mi, T.; Miyata, N. Synthesis and biological activity of optically active NCL-1, a lysine-specific demethylase 1 selective inhibitor. Bioorg. Med. Chem., 2011, 19(12), 3702-3708.
[http://dx.doi.org/10.1016/j.bmc.2010.12.024] [PMID: 21227703]
[121]
(a) Yin, W.; Arkilo, D.; Khudyakov, P.; Hazel, J.; Gupta, S.; Quinton, M.S.; Lin, J.; Hartman, D.S.; Bednar, M.M.; Rosen, L.; Wendland, J.R. Safety, pharmacokinetics and pharmacodynamics of TAK-418, a novel inhibitor of the epigenetic modulator lysine-specific deme-thylase 1A. Br. J. Clin. Pharmacol., 2021, 87(12), 4756-4768.
[http://dx.doi.org/10.1111/bcp.14912] [PMID: 33990969]
(b) Baba, R.; Matsuda, S.; Arakawa, Y.; Yamada, R.; Suzuki, N.; Ando, T.; Oki, H.; Igaki, S.; Daini, M.; Hattori, Y.; Matsumoto, S.; Ito, M.; Nakatani, A.; Kimura, H. LSD1 enzyme inhibitor TAK-418 unlocks aberrant epigenetic machinery and improves autism symptoms in neurodevelopmental disorder models. Sci. Adv., 2021, 7(11), eaba1187.
[http://dx.doi.org/10.1126/sciadv.aba1187] [PMID: 33712455]
[122]
Engel, M.; Gee, Y.S.; Cross, D.; Maccarone, A.; Heng, B.; Hulme, A.; Smith, G.; Guillemin, G.J.; Stringer, B.W.; Hyland, C.J.T.; Ooi, L. Novel dual-action prodrug triggers apoptosis in glioblastoma cells by releasing a glutathione quencher and lysine-specific histone deme-thylase 1A inhibitor. J. Neurochem., 2019, 149(4), 535-550.
[http://dx.doi.org/10.1111/jnc.14655] [PMID: 30592774]
[123]
Herrlinger, E.M.; Hau, M.; Redhaber, D.M.; Greve, G.; Willmann, D.; Steimle, S.; Müller, M.; Lübbert, M.; Miething, C.C.; Schüle, R.; Jung, M. Nitroreductase-mediated release of inhibitors of lysine-specific demethylase 1 (LSD1) from prodrugs in transfected acute mye-loid leukaemia cells. ChemBioChem, 2020, 21(16), 2329-2347.
[http://dx.doi.org/10.1002/cbic.202000138] [PMID: 32227662]
[124]
Zhou, Y.; Li, Y.; Wang, W.J.; Xiang, P.; Luo, X.M.; Yang, L.; Yang, S.Y.; Zhao, Y.L. Synthesis and biological evaluation of novel (E)-N′-(2,3-dihydro-1H-inden-1-ylidene) benzohydrazides as potent LSD1 inhibitors. Bioorg. Med. Chem. Lett., 2016, 26(18), 4552-4557.
[http://dx.doi.org/10.1016/j.bmcl.2015.06.054] [PMID: 27524309]
[125]
Li, Y.; Tao, L.; Zuo, Z.; Zhou, Y.; Qian, X.; Lin, Y.; Jie, H.; Liu, C.; Li, Z.; Zhang, H.; Zhang, H.; Cen, X.; Yang, S.; Zhao, Y. ZY0511, a novel, potent and selective LSD1 inhibitor, exhibits anticancer activity against solid tumors via the DDIT4/mTOR pathway. Cancer Lett., 2019, 454, 179-190.
[http://dx.doi.org/10.1016/j.canlet.2019.03.052] [PMID: 30978443]