A Quinquennial Review of Potent LSD1 Inhibitors Explored for the
Treatment of Different Cancers, with Special Focus on SAR Studies

Khursheed   Ahmad   Sheikh; Ashif      Iqubal; Mohammad   Mumtaz   Alam; Mymoona      Akhter; Mohammad   Ahmed   Khan; Syed      Ehtaishamul Haque; Suhel      Parvez; Umar      Jahangir; Mohammad      Amir; Suruchi      Khanna; Mohammad      Shaquiquzzaman
Abstract

Cancer bears a significant share of global mortality. The enzyme Lysine Specific Demethylase 1 (LSD1, also known as KDM1A), since its discovery in 2004, has captured the attention of cancer researchers due to its overexpression in several cancers like acute myeloid leukaemia (AML), solid tumours, etc. The Lysine Specific Demethylase (LSD1) downregulation is reported to have an effect on cancer proliferation, migration, and invasion. Therefore, research to discover safer and more potent LSD1 inhibitors can pave the way for the development of better cancer therapeutics. These efforts have resulted in the synthesis of many types of derivatives containing diverse structural nuclei. The present manuscript describes the role of Lysine Specific Demethylase 1 (LSD1) in carcinogenesis, reviews the LSD1 inhibitors explored in the past five years and discusses their comprehensive structural activity characteristics apart from the thorough description of LSD1. Besides, the potential challenges, opportunities, and future perspectives in the development of LSD1 inhibitors are also discussed. The review suggests that tranylcypromine derivatives are the most promising potent LSD1 inhibitors, followed by triazole and pyrimidine derivatives with IC₅₀ values in the nanomolar and sub-micromolar range. A number of potent LSD1 inhibitors derived from natural sources like resveratrol, protoberberine alkaloids, curcumin, etc. are also discussed. The structural-activity relationships discussed in the manuscript can be exploited to design potent and relatively safer LSD1 inhibitors as anticancer agents.
[1]
Nepali, K.; Sharma, S.; Sharma, M.; Bedi, P.M.S.; Dhar, K.L. Rational approaches, design strategies, structure activity relationship and mechanistic insights for anticancer hybrids. Eur. J. Med. Chem.,  2014, 77, 422-487.
 [http://dx.doi.org/10.1016/j.ejmech.2014.03.018] [PMID: 24685980]

[2]
Mareel, M.; Leroy, A. Clinical, cellular, and molecular aspects of cancer invasion. Physiol. Rev.,  2003, 83(2), 337-376.
 [http://dx.doi.org/10.1152/physrev.00024.2002] [PMID: 12663862]

[3]
Wesche, J.; Haglund, K.; Haugsten, E.M. Fibroblast growth factors and their receptors in cancer. Biochem. J.,  2011, 437(2), 199-213.
 [http://dx.doi.org/10.1042/BJ20101603] [PMID: 21711248]

[4]
GLOBOCAN. The global cancer observatory - All cancers. Int. Agency Res. Cancer,  2020, 419, 199-200.

[5]
Jemal, A.; Bray, F.; Center, M.M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA Cancer J. Clin.,  2011, 61(2), 69-90.
 [http://dx.doi.org/10.3322/caac.20107] [PMID: 21296855]

[6]
Kim, S.K. Handbook of Anticancer Drugs from Marine Origin; Springer, 2015, pp. 1-805.
 [http://dx.doi.org/10.1007/978-3-319-07145-9]

[7]
Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer,  2015, 136(5), E359-E386.
 [http://dx.doi.org/10.1002/ijc.29210] [PMID: 25220842]

[8]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin.,  2018, 68(6), 394-424.
 [http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]

[9]
de Martel, C.; Georges, D.; Bray, F.; Ferlay, J.; Clifford, G.M. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob. Health,  2020, 8(2), e180-e190.
 [http://dx.doi.org/10.1016/S2214-109X(19)30488-7] [PMID: 31862245]

[10]
Torre, L.A.; Bray, F.; Siegel, R.L.; Ferlay, J.; Lortet-Tieulent, J.; Jemal, A. Global cancer statistics, 2012. CA Cancer J. Clin.,  2015, 65(2), 87-108.
 [http://dx.doi.org/10.3322/caac.21262] [PMID: 25651787]

[11]
Akavia, U.D.; Litvin, O.; Kim, J.; Sanchez-Garcia, F.; Kotliar, D.; Causton, H.C.; Pochanard, P.; Mozes, E.; Garraway, L.A.; Pe’er, D. An integrated approach to uncover drivers of cancer. Cell,  2010, 143(6), 1005-1017.
 [http://dx.doi.org/10.1016/j.cell.2010.11.013] [PMID: 21129771]

[12]
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]

[13]
Tsai, H.C.; Baylin, S.B. Cancer epigenetics: linking basic biology to clinical medicine. Cell Res.,  2011, 21(3), 502-517.
 [http://dx.doi.org/10.1038/cr.2011.24] [PMID: 21321605]

[14]
Metzger, E.; Wissmann, M.; Yin, N.; Müller, J.M.; Schneider, R.; Peters, A.H.F.M.; 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]

[15]
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]

[16]
Kim, S.; Benoiton, L.; Paik, W.K. ε-Alkyllysinase. J. Biol. Chem.,  1964, 239(11), 3790-3796.
 [http://dx.doi.org/10.1016/S0021-9258(18)91206-8] [PMID: 14257609]

[17]
Shi, Y.; Lan, F.; Matson, C.; Mulligan, P.; Whetstine, J.R.; Cole, P.A.; Casero, R.A.; Shi, Y. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell,  2004, 119(7), 941-953.
 [http://dx.doi.org/10.1016/j.cell.2004.12.012] [PMID: 15620353]

[18]
Hakimi, M.A.; Bochar, D.A.; Chenoweth, J.; Lane, W.S.; Mandel, G.; Shiekhattar, R. A core–BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes. Proc. Natl. Acad. Sci. USA,  2002, 99(11), 7420-7425.
 [http://dx.doi.org/10.1073/pnas.112008599] [PMID: 12032298]

[19]
You, A.; Tong, J.K.; Grozinger, C.M.; Schreiber, S.L. CoREST is an integral component of the CoREST- human histone deacetylase complex. Proc. Natl. Acad. Sci. USA,  2001, 98(4), 1454-1458.
 [http://dx.doi.org/10.1073/pnas.98.4.1454] [PMID: 11171972]

[20]
Battaglioli, E.; Andrés, M.E.; Rose, D.W.; Chenoweth, J.G.; Rosenfeld, M.G.; Anderson, M.E.; Mandel, G. REST repression of neuronal genes requires components of the hSWI.SNF complex. J. Biol. Chem.,  2002, 277(43), 41038-41045.
 [http://dx.doi.org/10.1074/jbc.M205691200] [PMID: 12192000]

[21]
Lee, M.G.; Wynder, C.; Cooch, N.; Shiekhattar, R. An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation. Nature,  2005, 437(7057), 432-435.
 [http://dx.doi.org/10.1038/nature04021] [PMID: 16079794]

[22]
Tsukada, Y.; Fang, J.; Erdjument-Bromage, H.; Warren, M.E.; Borchers, C.H.; Tempst, P.; Zhang, Y. Histone demethylation by a family of JmjC domain-containing proteins. Nature,  2006, 439(7078), 811-816.
 [http://dx.doi.org/10.1038/nature04433] [PMID: 16362057]

[23]
Johansson, C.; Velupillai, S.; Tumber, A.; Szykowska, A.; Hookway, E.S.; Nowak, R.P.; Strain-Damerell, C.; Gileadi, C.; Philpott, M.; Burgess-Brown, N.; Wu, N.; Kopec, J.; Nuzzi, A.; Steuber, H.; Egner, U.; Badock, V.; Munro, S.; LaThangue, N.B.; Westaway, S.; Brown, J.; Athanasou, N.; Prinjha, R.; Brennan, P.E.; Oppermann, U. Structural analysis of human KDM5B guides histone demethylase inhibitor development. Nat. Chem. Biol.,  2016, 12(7), 539-545.
 [http://dx.doi.org/10.1038/nchembio.2087] [PMID: 27214403]

[24]
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]

[25]
Lienhart, W.D.; Gudipati, V.; Macheroux, P. The human flavoproteome. Arch. Biochem. Biophys.,  2013, 535(2), 150-162.
 [http://dx.doi.org/10.1016/j.abb.2013.02.015] [PMID: 23500531]

[26]
Spannhoff, A.; Hauser, A.T.; Heinke, R.; Sippl, W.; Jung, M. The emerging therapeutic potential of histone methyltransferase and demethylase inhibitors. ChemMedChem,  2009, 4(10), 1568-1582.
 [http://dx.doi.org/10.1002/cmdc.200900301] [PMID: 19739196]

[27]
Fang, R.; Barbera, A.J.; Xu, Y.; Rutenberg, M.; Leonor, T.; Bi, Q.; Lan, F.; Mei, P.; Yuan, G.C.; Lian, C.; Peng, J.; Cheng, D.; Sui, G.; Kaiser, U.B.; Shi, Y.; Shi, Y.G. Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating intragenic H3K4me2 methylation. Mol. Cell,  2010, 39(2), 222-233.
 [http://dx.doi.org/10.1016/j.molcel.2010.07.008] [PMID: 20670891]

[28]
Forneris, F.; Binda, C.; Battaglioli, E.; Mattevi, A. LSD1: oxidative chemistry for multifaceted functions in chromatin regulation. Trends Biochem. Sci.,  2008, 33(4), 181-189.
 [http://dx.doi.org/10.1016/j.tibs.2008.01.003] [PMID: 18343668]

[29]
Yang, M.; Gocke, C.B.; Luo, X.; Borek, D.; Tomchick, D.R.; Machius, M.; Otwinowski, Z.; Yu, H. Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase. Mol. Cell,  2006, 23(3), 377-387.
 [http://dx.doi.org/10.1016/j.molcel.2006.07.012] [PMID: 16885027]

[30]
Ciccone, D.N.; Su, H.; Hevi, S.; Gay, F.; Lei, H.; Bajko, J.; Xu, G.; Li, E.; Chen, T. KDM1B is a histone H3K4 demethylase required to establish maternal genomic imprints. Nature,  2009, 461(7262), 415-418.
 [http://dx.doi.org/10.1038/nature08315] [PMID: 19727073]

[31]
Shi, Y.J.; Matson, C.; Lan, F.; Iwase, S.; Baba, T.; Shi, Y. Regulation of LSD1 histone demethylase activity by its associated factors. Mol. Cell,  2005, 19(6), 857-864.
 [http://dx.doi.org/10.1016/j.molcel.2005.08.027] [PMID: 16140033]

[32]
Culhane, J.C.; Cole, P.A. LSD1 and the chemistry of histone demethylation. Curr. Opin. Chem. Biol.,  2007, 11(5), 561-568.
 [http://dx.doi.org/10.1016/j.cbpa.2007.07.014] [PMID: 17851108]

[33]
Yang, M.; Culhane, J.C.; Szewczuk, L.M.; Gocke, C.B.; Brautigam, C.A.; Tomchick, D.R.; Machius, M.; Cole, P.A.; Yu, H. Structural basis of histone demethylation by LSD1 revealed by suicide inactivation. Nat. Struct. Mol. Biol.,  2007, 14(6), 535-539.
 [http://dx.doi.org/10.1038/nsmb1255] [PMID: 17529991]

[34]
Forneris, F.; Binda, C.; Vanoni, M.A.; Battaglioli, E.; Mattevi, A. Human histone demethylase LSD1 reads the histone code. J. Biol. Chem.,  2005, 280(50), 41360-41365.
 [http://dx.doi.org/10.1074/jbc.M509549200] [PMID: 16223729]

[35]
Forneris, F.; Binda, C.; Dall’Aglio, A.; Fraaije, M.W.; Battaglioli, E.; Mattevi, A. A highly specific mechanism of histone H3-K4 recognition by histone demethylase LSD1. J. Biol. Chem.,  2006, 281(46), 35289-35295.
 [http://dx.doi.org/10.1074/jbc.M607411200] [PMID: 16987819]

[36]
Tu, W.J.; McCuaig, R.D.; Tan, A.H.Y.; Hardy, K.; Seddiki, N.; Ali, S.; Dahlstrom, J.E.; Bean, E.G.; Dunn, J.; Forwood, J.; Tsimbalyuk, S.; Smith, K.; Yip, D.; Malik, L.; Prasanna, T.; Milburn, P.; Rao, S. Targeting nuclear LSD1 to reprogram cancer cells and reinvigorate exhausted T cells via a novel LSD1-EOMES switch. Front. Immunol.,  2020, 11, 1228.
 [http://dx.doi.org/10.3389/fimmu.2020.01228] [PMID: 32612611]

[37]
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,  2021, 11(3), 621-631.
 [http://dx.doi.org/10.1016/j.apsb.2020.06.007] [PMID: 32837872]

[38]
Yang, G.J.; Lei, P.M.; Wong, S.Y.; Ma, D.L.; Leung, C.H. Pharmacological inhibition of LSD1 for cancer treatment. Molecules,  2018, 23(12), 3194.
 [http://dx.doi.org/10.3390/molecules23123194] [PMID: 30518104]

[39]
Lim, S.; Janzer, A.; Becker, A.; Zimmer, A.; Schüle, R.; Buettner, R.; Kirfel, J. Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology. Carcinogenesis,  2010, 31(3), 512-520.
 [http://dx.doi.org/10.1093/carcin/bgp324] [PMID: 20042638]

[40]
Sheng, W.; LaFleur, M.W.; Nguyen, T.H.; Chen, S.; Chakravarthy, A.; Conway, J.R.; Li, Y.; Chen, H.; Yang, H.; Hsu, P.H.; Van Allen, E.M.; Freeman, G.J.; De Carvalho, D.D.; He, H.H.; Sharpe, A.H.; Shi, Y. LSD1 Ablation stimulates anti-tumor immunity and enables checkpoint blockade. Cell,  2018, 174(3), 549-563.e19.
 [http://dx.doi.org/10.1016/j.cell.2018.05.052] [PMID: 29937226]

[41]
Zheng, Y.C.; Yu, B.; Chen, Z.S.; Liu, Y.; Liu, H.M. TCPs: privileged scaffolds for identifying potent LSD1 inhibitors for cancer therapy. Epigenomics,  2016, 8(5), 651-666.
 [http://dx.doi.org/10.2217/epi-2015-0002] [PMID: 27102879]

[42]
Hoshino, I.; Takahashi, M.; Akutsu, Y.; Murakami, K.; Matsumoto, Y.; Suito, H.; Sekino, N.; Komatsu, A.; Iida, K.; Suzuki, T.; Inoue, I.; Ishige, F.; Iwatate, Y.; Matsubara, H. Genome wide ChIP seq data with a transcriptome analysis reveals the groups of genes regulated by histone demethylase LSD1 inhibition in esophageal squamous cell carcinoma cells. Oncol. Lett.,  2019, 18(1), 872-881.
 [http://dx.doi.org/10.3892/ol.2019.10350] [PMID: 31289565]

[43]
Ueda, R.; Suzuki, T.; Mino, K.; Tsumoto, H.; Nakagawa, H.; Hasegawa, M.; Sasaki, R.; Mizukami, T.; Miyata, N. Identification of cell-active lysine specific demethylase 1-selective inhibitors. J. Am. Chem. Soc.,  2009, 131(48), 17536-17537.
 [http://dx.doi.org/10.1021/ja907055q] [PMID: 19950987]

[44]
Binda, C.; Valente, S.; Romanenghi, M.; Pilotto, S.; Cirilli, R.; Karytinos, A.; Ciossani, G.; Botrugno, O.A.; Forneris, F.; Tardugno, M.; Edmondson, D.E.; Minucci, S.; Mattevi, A.; Mai, A. Biochemical, structural, and biological evaluation of tranylcypromine derivatives as inhibitors of histone demethylases LSD1 and LSD2. J. Am. Chem. Soc.,  2010, 132(19), 6827-6833.
 [http://dx.doi.org/10.1021/ja101557k] [PMID: 20415477]

[45]
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]

[46]
Escoubet-Lozach, L.; Lin, I.L.; Jensen-Pergakes, K.; Brady, H.A.; Gandhi, A.K.; Schafer, P.H.; Muller, G.W.; Worland, P.J.; Chan, K.W.H.; Verhelle, D. Pomalidomide and lenalidomide induce p21 WAF-1 expression in both lymphoma and multiple myeloma through a LSD1-mediated epigenetic mechanism. Cancer Res.,  2009, 69(18), 7347-7356.
 [http://dx.doi.org/10.1158/0008-5472.CAN-08-4898] [PMID: 19738071]

[47]
Shi, Y.; Wu, Y.R.; Su, M.B.; Shen, D.H.; Gunosewoyo, H.; Yang, F.; Li, J.; Tang, J.; Zhou, Y.B.; Yu, L.F. Novel spirocyclic tranylcypromine derivatives as lysine-specific demethylase 1 (LSD1) inhibitors. RSC Advances,  2018, 8(3), 1666-1676.
 [http://dx.doi.org/10.1039/C7RA13097J] [PMID: 35540911]

[48]
Zhou, C.; Wu, F.; Lu, L.; Wei, L.; Pai, E.; Yao, Y.; Song, Y. Structure activity relationship and modeling studies of inhibitors of lysine specific demethylase 1. PLoS One,  2017, 12(2), e0170301.
 [http://dx.doi.org/10.1371/journal.pone.0170301] [PMID: 28158205]

[49]
Liang, L.; Wang, H.; Du, Y.; Luo, B.; Meng, N.; Cen, M.; Huang, P.; Ganesan, A.; Wen, S. New tranylcypromine derivatives containing sulfonamide motif as potent LSD1 inhibitors to target acute myeloid leukemia: Design, synthesis and biological evaluation. Bioorg. Chem.,  2020, 99, 103808.
 [http://dx.doi.org/10.1016/j.bioorg.2020.103808] [PMID: 32334189]

[50]
Sun, K.; Peng, J.D.; Suo, F.Z.; Zhang, T.; Fu, Y.D.; Zheng, Y.C.; Liu, H.M. Discovery of tranylcypromine analogs with an acylhydrazone substituent as LSD1 inactivators: Design, synthesis and their biological evaluation. Bioorg. Med. Chem. Lett.,  2017, 27(22), 5036-5039.
 [http://dx.doi.org/10.1016/j.bmcl.2017.10.003] [PMID: 29037950]

[51]
Trifirò, P.; Cappa, A.; Brambillasca, S.; Botrugno, O.A.; Cera, M.R.; Zuffo, R.D.; Dessanti, P.; Meroni, G.; Thaler, F.; Villa, M.; Minucci, S.; Mercurio, C.; Varasi, M.; Vianello, P. Novel potent inhibitors of the histone demethylase KDM1A (LSD1), orally active in a murine promyelocitic leukemia model. Future Med. Chem.,  2017, 9(11), 1161-1174.
 [http://dx.doi.org/10.4155/fmc-2017-0003] [PMID: 28722470]

[52]
Kakizawa, T.; Ota, Y.; Itoh, Y.; Suzuki, T. Histone H3 peptides incorporating modified lysine residues as lysine-specific demethylase 1 inhibitors. Bioorg. Med. Chem. Lett.,  2018, 28(2), 167-169.
 [http://dx.doi.org/10.1016/j.bmcl.2017.11.035] [PMID: 29198865]

[53]
Borrello, M.T.; Schinor, B.; Bartels, K.; Benelkebir, H.; Pereira, S.; Al-Jamal, W.T.; Douglas, L.; Duriez, P.J.; Packham, G.; Haufe, G.; Ganesan, A. Fluorinated tranylcypromine analogues as inhibitors of lysine-specific demethylase 1 (LSD1, KDM1A). Bioorg. Med. Chem. Lett.,  2017, 27(10), 2099-2101.
 [http://dx.doi.org/10.1016/j.bmcl.2017.03.081] [PMID: 28390942]

[54]
Fioravanti, R.; Romanelli, A.; Mautone, N.; Di Bello, E.; Rovere, A.; Corinti, D.; Zwergel, C.; Valente, S.; Rotili, D.; Botrugno, O.A.; Dessanti, P.; Vultaggio, S.; Vianello, P.; Cappa, A.; Binda, C.; Mattevi, A.; Minucci, S.; Mercurio, C.; Varasi, M.; Mai, A. Tranylcypromine-based LSD1 inhibitors: Structure-activity relationships, antiproliferative effects in leukemia, and gene target modulation. ChemMedChem,  2020, 15(7), 643-658.
 [http://dx.doi.org/10.1002/cmdc.201900730] [PMID: 32003940]

[55]
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]

[56]
Ota, Y.; Miyamura, S.; Araki, M.; Itoh, Y.; Yasuda, S.; Masuda, M.; Taniguchi, T.; Sowa, Y.; Sakai, T.; Itami, K.; Yamaguchi, J.; Suzuki, T. Design, synthesis and evaluation of γ-turn mimetics as LSD1-selective inhibitors. Bioorg. Med. Chem.,  2018, 26(3), 775-785.
 [http://dx.doi.org/10.1016/j.bmc.2017.12.045] [PMID: 29331452]

[57]
Milelli, A.; Marchetti, C.; Turrini, E.; Catanzaro, E.; Mazzone, R.; Tomaselli, D.; Fimognari, C.; Tumiatti, V.; Minarini, A. Novel polyamine-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]

[58]
Ota, Y.; Nakamura, A.; Elboray, E.E.; Itoh, Y.; Suzuki, T. Design, synthesis, and biological evaluation of a conjugate of 5-fluorouracil and an LSD1 inhibitor. Chem. Pharm. Bull. (Tokyo),  2019, 67(3), 192-195.
 [http://dx.doi.org/10.1248/cpb.c18-00577] [PMID: 30369513]

[59]
Ota, Y.; Kakizawa, T.; Itoh, Y.; Suzuki, T. Design, Synthesis, and In Vitro Evaluation of Novel Histone H3 Peptide-based LSD1 inactivators incorporating α,α-disubstituted amino acids with γ-turn-Inducing structures. Molecules,  2018, 23(5), 1099.
 [http://dx.doi.org/10.3390/molecules23051099] [PMID: 29734782]

[60]
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]

[61]
Naveen Sadhu, M.; 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(34), 127763.
 [http://dx.doi.org/10.1016/j.bmcl.2020.127763] [PMID: 33359604]

[62]
Huang, M.J.; Guo, J.W.; Fu, Y.D.; You, Y.Z.; Xu, W.Y.; Song, T.Y.; Li, R.; Chen, Z.T.; Huang, L.H.; Liu, H.M. Discovery of new tranylcypromine derivatives as highly potent LSD1 inhibitors. Bioorg. Med. Chem. Lett.,  2021, 41(41), 127993.
 [http://dx.doi.org/10.1016/j.bmcl.2021.127993] [PMID: 33775841]

[63]
Teresa Borrello, M.; Benelkebir, H.; Lee, A.; Hin Tam, C.; Shafat, M.; Rushworth, S.A.; Bowles, K.M.; Douglas, L.; Duriez, P.J.; Bailey, S.; Crabb, S.J.; Packham, G.; Ganesan, A. Tranylcypromine Analogues as LSD1 (KDM1A) inhibitors targeting acute myeloid leukemia. ChemMedChem,  2021, 16(8), 1316-1324.
 [http://dx.doi.org/10.1002/cmdc.202000754] [PMID: 33533576]

[64]
Ji, Y.Y.; Lin, S.D.; Wang, Y.J.; Su, M.B.; Zhang, W.; Gunosewoyo, H.; Yang, F.; Li, J.; Tang, J.; Zhou, Y.B.; Yu, L.F. Tying up tranylcypromine: Novel selective histone lysine specific demethylase 1 (LSD1) inhibitors. Eur. J. Med. Chem.,  2017, 141, 101-112.
 [http://dx.doi.org/10.1016/j.ejmech.2017.09.073] [PMID: 29031059]

[65]
Holshouser, S.; Dunworth, M.; Stewart, T.M.; Peterson, Y.K.; Burger, P.; Kirkpatrick, J.; Chen, H-H.; Robert, A. Dual inhibitors of LSD1 and spermine oxidase. AIChE Annu. Meet. Conf. Proc,  2019, 10(5), pp. 778-790.
 [http://dx.doi.org/10.1039/c8md00610e]

[66]
Li, Z.R.; Wang, S.; Yang, L.; Yuan, X.H.; Suo, F.Z.; Yu, B.; Liu, H.M. Experience-based discovery (EBD) of aryl hydrazines as new scaffolds for the development of LSD1/KDM1A inhibitors. Eur. J. Med. Chem.,  2019, 166, 432-444.
 [http://dx.doi.org/10.1016/j.ejmech.2019.01.075] [PMID: 30739825]

[67]
Li, Z.H.; Liu, X.Q.; Geng, P.F.; Suo, F.Z.; Ma, J.L.; Yu, B.; Zhao, T.Q.; Zhou, Z.Q.; Huang, C.X.; Zheng, Y.C.; Liu, H.M. Discovery of [1,2,3]Triazolo[4,5- d ]pyrimidine derivatives as novel LSD1 inhibitors. ACS Med. Chem. Lett.,  2017, 8(4), 384-389.
 [http://dx.doi.org/10.1021/acsmedchemlett.6b00423] [PMID: 28435523]

[68]
Li, Z.H.; Ma, J.L.; Liu, G.Z.; Zhang, X.H.; Qin, T.T.; Ren, W.H.; Zhao, T.Q.; Chen, X.H.; Zhang, Z.Q. [1,2,3]Triazolo[4,5-d]pyrimidine derivatives incorporating (thio)urea moiety as a novel scaffold for LSD1 inhibitors. Eur. J. Med. Chem.,  2020, 187, 111989.
 [http://dx.doi.org/10.1016/j.ejmech.2019.111989] [PMID: 31881456]

[69]
Wang, S.; Li, Z.R.; Suo, F.Z.; Yuan, X.H.; Yu, B.; Liu, H.M. Synthesis, structure-activity relationship studies and biological characterization of new [1,2,4]triazolo[1,5-a]pyrimidine-based LSD1/KDM1A inhibitors. Eur. J. Med. Chem.,  2019, 167, 388-401.
 [http://dx.doi.org/10.1016/j.ejmech.2019.02.039] [PMID: 30780087]

[70]
Li, Z.; Ding, L.; Li, Z.; Wang, Z.; Suo, F.; Shen, D.; Zhao, T.; Sun, X.; Wang, J.; Liu, Y.; Ma, L.; Zhao, B.; Geng, P.; Yu, B.; Zheng, Y.; Liu, H. Development of the triazole-fused pyrimidine derivatives as highly potent and reversible inhibitors of histone lysine specific demethylase 1 (LSD1/KDM1A). Acta Pharm. Sin. B,  2019, 9(4), 794-808.
 [http://dx.doi.org/10.1016/j.apsb.2019.01.001] [PMID: 31384539]

[71]
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, 940-951.
 [http://dx.doi.org/10.1016/j.ejmech.2016.10.021] [PMID: 27769034]

[72]
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]

[73]
Ma, L.; Wang, H.; You, Y.; Ma, C.; Liu, Y.; Yang, F.; Zheng, Y.; Liu, H. Exploration of 5-cyano-6-phenyl- pyrimidin 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]
Metwally, N.H.; Mohamed, M.S.; Ragb, E.A. Design, synthesis, anticancer evaluation, molecular docking and cell cycle analysis of 3-methyl-4,7-dihydropyrazolo[1,5-a] pyrimidine derivatives as potent histone lysine demethylases (KDM) inhibitors and apoptosis inducers. Bioorg. Chem.,  2019, 88(April), 102929.
 [http://dx.doi.org/10.1016/j.bioorg.2019.102929] [PMID: 31015179]

[75]
Kanouni, T.; Severin, C.; Cho, R.W.; Yuen, N.Y.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]

[76]
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 xanthine 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]

[77]
Wang, J.; Zhang, X.; Yan, J.; Li, W.; Jiang, Q.; Wang, X.; Zhao, D.; Cheng, M. Design, synthesis and biological evaluation of curcumin analogues as novel LSD1 inhibitors. Bioorg. Med. Chem. Lett.,  2019, 29(23), 126683.
 [http://dx.doi.org/10.1016/j.bmcl.2019.126683] [PMID: 31627991]

[78]
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]

[79]
Kumarasinghe, I.R.; Woster, P.M. Synthesis and evaluation of novel cyclic Peptide inhibitors of lysine-specific demethylase 1. ACS Med. Chem. Lett.,  2014, 5(1), 29-33.
 [http://dx.doi.org/10.1021/ml4002997] [PMID: 24883177]

[80]
Kumarasinghe, I.R.; Woster, P.M. Cyclic peptide inhibitors of lysine-specific demethylase 1 with improved potency identified by alanine scanning mutagenesis. Eur. J. Med. Chem.,  2018, 148, 210-220.
 [http://dx.doi.org/10.1016/j.ejmech.2018.01.098] [PMID: 29459279]

[81]
T. Hart, P.; Openy, J.; Krzyzanowski, A.; Adihou, H.; Waldmann, H. Hot-spot guided design of macrocyclic inhibitors of the LSD1-CoREST1 interaction. Tetrahedron,  2019, 75(48), 130685.
 [http://dx.doi.org/10.1016/j.tet.2019.130685]

[82]
Xu, Y.; He, Z.; Liu, H.; Chen, Y.; Gao, Y.; Zhang, S.; Wang, M.; Lu, X.; Wang, C.; Zhao, Z.; Liu, Y.; Zhao, J.; Yu, Y.; Yang, M. 3D-QSAR, molecular docking, and molecular dynamics simulation study of thieno[3,2-b]pyrrole-5-carboxamide derivatives as LSD1 inhibitors. RSC Advances,  2020, 10(12), 6927-6943.
 [http://dx.doi.org/10.1039/C9RA10085G] [PMID: 35493862]

[83]
Romussi, A.; Cappa, A.; Vianello, P.; Brambillasca, S.; Cera, M.R.; Dal Zuffo, R.; Fagà, G.; Fattori, R.; Moretti, L.; Trifirò, P.; Villa, M.; Vultaggio, S.; Cecatiello, V.; Pasqualato, S.; Dondio, G.; So, C.W.E.; Minucci, S.; Sartori, L.; Varasi, M.; Mercurio, C. Discovery of reversible inhibitors of KDM1A efficacious in acute myeloid leukemia models. ACS Med. Chem. Lett.,  2020, 11(5), 754-759.
 [http://dx.doi.org/10.1021/acsmedchemlett.9b00604] [PMID: 32435381]

[84]
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 histone 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]

[85]
Vianello, P.; Sartori, L.; 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.; Botrugno, O.A.; Dessanti, P.; Minucci, S.; Vultaggio, S.; Zagarrí, E.; Varasi, M.; Mercurio, C. Thieno[3,2- b ]pyrrole-5-carboxamides as new reversible inhibitors of histone lysine demethylase KDM1A/LSD1. Part 2: structure-based drug design and structure–activity relationship. J. Med. Chem.,  2017, 60(5), 1693-1715.
 [http://dx.doi.org/10.1021/acs.jmedchem.6b01019] [PMID: 28186757]

[86]
Xi, J.; Xu, S.; Wu, L.; Ma, T.; Liu, R.; Liu, Y.C.; Deng, D.; Gu, Y.; Zhou, J.; Lan, F.; Zha, X. Design, synthesis and biological activity of 3-oxoamino-benzenesulfonamides as selective and reversible LSD1 inhibitors. Bioorg. Chem.,  2017, 72, 182-189.
 [http://dx.doi.org/10.1016/j.bioorg.2017.04.006] [PMID: 28460360]

[87]
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, 112243.
 [http://dx.doi.org/10.1016/j.ejmech.2020.112243] [PMID: 32229389]

[88]
Li, Z.R.; Suo, F.Z.; Guo, Y.J.; Cheng, H.F.; Niu, S.H.; Shen, D.D.; Zhao, L.J.; Liu, Z.Z.; Maa, M.; Yu, B.; Zheng, Y.C.; Liu, H.M. Natural protoberberine alkaloids, identified as potent selective LSD1 inhibitors, induce AML cell differentiation. Bioorg. Chem.,  2020, 97, 103648.
 [http://dx.doi.org/10.1016/j.bioorg.2020.103648] [PMID: 32065882]

[89]
He, X.; Gao, Y.; Hui, Z.; Shen, G.; Wang, S.; Xie, T.; Ye, X.Y. 4-Hydroxy-3-methylbenzofuran-2-carbohydrazones as novel LSD1 inhibitors. Bioorg. Med. Chem. Lett.,  2020, 30(10), 127109.
 [http://dx.doi.org/10.1016/j.bmcl.2020.127109] [PMID: 32201021]

[90]
Gehling, V.S.; McGrath, J.P.; Duplessis, M.; Khanna, A.; Brucelle, F.; Vaswani, R.G.; Côté, A.; Stuckey, J.; Watson, V.; Cummings, R.T.; Balasubramanian, S.; Iyer, P.; Sawant, P.; Good, A.C.; Albrecht, B.K.; Harmange, J.C.; Audia, J.E.; Bellon, S.F.; Trojer, P.; Levell, J.R. Design and synthesis of styrenylcyclopropylamine LSD1 inhibitors. ACS Med. Chem. Lett.,  2020, 11(6), 1213-1220.
 [http://dx.doi.org/10.1021/acsmedchemlett.0c00060] [PMID: 32551003]

[91]
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]

[92]
Duan, Y.; Qin, W.; Suo, F.; Zhai, X.; Guan, Y.; Wang, X.; Zheng, Y.; Liu, H. Design, synthesis and in vitro evaluation of stilbene derivatives as novel LSD1 inhibitors for AML therapy. Bioorg. Med. Chem.,  2018, 26(23-24), 6000-6014.
 [http://dx.doi.org/10.1016/j.bmc.2018.10.037] [PMID: 30448189]

[93]
Duan, Y.C.; Guan, Y.Y.; Zhai, X.Y.; Ding, L.N.; Qin, W.P.; Shen, D.D.; Liu, X.Q.; Sun, X.D.; Zheng, Y.C.; Liu, H.M. Discovery of resveratrol derivatives as novel LSD1 inhibitors: Design, synthesis and their biological evaluation. Eur. J. Med. Chem.,  2017, 126, 246-258.
 [http://dx.doi.org/10.1016/j.ejmech.2016.11.035] [PMID: 27888721]

[94]
Nie, Z.; Shi, L.; Lai, C.; Severin, C.; Xu, J.; Del Rosario, J.R.; Stansfield, R.K.; Cho, R.W.; Kanouni, T.; Veal, J.M.; Stafford, J.A.; Chen, Y.K. Structure-based design and discovery of potent and selective lysine-specific demethylase 1 (LSD1) inhibitors. Bioorg. Med. Chem. Lett.,  2019, 29(1), 103-106.
 [http://dx.doi.org/10.1016/j.bmcl.2018.11.001] [PMID: 30409536]

[95]
Umezawa, N.; Tsuji, K.; Sato, S.; Kikuchi, M.; Watanabe, H.; Horai, Y.; Yamaguchi, M.; Hisamatsu, Y.; Umehara, T.; Higuchi, T. Inhibition of FAD-dependent lysine-specific demethylases by chiral polyamine analogues. RSC Advances,  2018, 8(64), 36895-36902.
 [http://dx.doi.org/10.1039/C8RA07879C] [PMID: 35558920]

[96]
Mould, D.P.; Bremberg, U.; Jordan, A.M.; Geitmann, M.; McGonagle, A.E.; Somervaille, T.C.P.; Spencer, G.J.; Ogilvie, D.J. Development and evaluation of 4-(pyrrolidin-3-yl)benzonitrile derivatives as inhibitors of lysine specific demethylase 1. Bioorg. Med. Chem. Lett.,  2017, 27(20), 4755-4759.
 [http://dx.doi.org/10.1016/j.bmcl.2017.08.052] [PMID: 28927796]

[97]
Yang, C.; Wang, W.; Liang, J.X.; Li, G.; Vellaisamy, K.; Wong, C.Y.; Ma, D.L.; Leung, C.H. A Rhodium(III)-based inhibitor of lysine-specific histone demethylase 1 as an epigenetic modulator in prostate cancer cells. J. Med. Chem.,  2017, 60(6), 2597-2603.
 [http://dx.doi.org/10.1021/acs.jmedchem.7b00133] [PMID: 28219005]

[98]
Lin, Y.; Luo, J.; Li, L.; Liu, X.; Wang, W.; Zhu, L.; Han, C.; Kong, L. Precise separation of lysine-specific demethylase 1 inhibitors from Corydalis yanhusuo using multi-mode counter-current chromatography guided by virtual screening. J. Chromatogr. A,  2020, 1625, 461294.
 [http://dx.doi.org/10.1016/j.chroma.2020.461294] [PMID: 32709337]

[99]
Jia, G.; Cang, S.; Ma, P.; Song, Z. Capsaicin: A “hot” KDM1A/LSD1 inhibitor from peppers. Bioorg. Chem.,  2020, 103(August), 104161.
 [http://dx.doi.org/10.1016/j.bioorg.2020.104161] [PMID: 32889380]

[100]
Wang, L.; Li, L.; Han, Q.; Wang, X.; Zhao, D.; Liu, J. Identification and biological evaluation of natural product Biochanin A. Bioorg. Chem.,  2020, 97, 103674.
 [http://dx.doi.org/10.1016/j.bioorg.2020.103674] [PMID: 32097796]

[101]
Lin, Y.; Han, C.; Xu, Q.; Wang, W.; Li, L.; Zhu, D.; Luo, J.; Kong, L. Integrative countercurrent chromatography for the target isolation of lysine-specific demethylase 1 inhibitors from the roots of Salvia miltiorrhiza. Talanta,  2020, 206(206), 120195.
 [http://dx.doi.org/10.1016/j.talanta.2019.120195] [PMID: 31514831]

[102]
Ren, C.; Lin, Y.; Liu, X.; Yan, D.; Xu, X.; Zhu, D.; Kong, L.; Han, C. Target separation and antitumor metastasis activity of sesquiterpene-based lysine-specific demethylase 1 inhibitors from zedoary turmeric oil. Bioorg. Chem.,  2021, 108, 104666.
 [http://dx.doi.org/10.1016/j.bioorg.2021.104666] [PMID: 33550070]

[103]
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, 113453.
 [http://dx.doi.org/10.1016/j.ejmech.2021.113453] [PMID: 33957387]

[104]
He, M.; Ning, W.; Hu, Z.; Huang, J.; Dong, C.; Zhou, H.B. Design, synthesis and biological evaluation of novel dual-acting modulators targeting both estrogen receptor α (ERα) and lysine-specific demethylase 1 (LSD1) for treatment of breast cancer. Eur. J. Med. Chem.,  2020, 195, 112281.
 [http://dx.doi.org/10.1016/j.ejmech.2020.112281] [PMID: 32283297]

[105]
Li, Y.; Sun, Y.; Zhou, Y.; Li, X.; Zhang, H.; Zhang, G. Discovery of orally active chalcones as histone lysine specific demethylase 1 inhibitors for the treatment of leukaemia. J. Enzyme Inhib. Med. Chem.,  2021, 36(1), 207-217.
 [http://dx.doi.org/10.1080/14756366.2020.1852556] [PMID: 33307878]

[106]
Yan, J.; Gu, Y.; Sun, Y.; Zhang, Z.; Zhang, X.; Wang, X.; Wu, T.; Zhao, D.; Cheng, M. Design, synthesis, and biological evaluation of 5-aminotetrahydroquinoline-based LSD1 inhibitors acting on Asp375. Arch. Pharm. (Weinheim),  2021, 354(8), 2100102.
 [http://dx.doi.org/10.1002/ardp.202100102] [PMID: 33987875]

[107]
Zhang, X.; Huang, H.; Zhang, Z.; Yan, J.; Wu, T.; Yin, W.; Sun, Y.; Wang, X.; Gu, Y.; Zhao, D.; Cheng, M. Design, synthesis and biological evaluation of novel benzofuran derivatives as potent LSD1 inhibitors. Eur. J. Med. Chem.,  2021, 220, 113501.
 [http://dx.doi.org/10.1016/j.ejmech.2021.113501] [PMID: 33945992]

[108]
Hattori, Y.; Matsuda, S.; Baba, R.; Matsumiya, K.; Iwasaki, S.; Constantinescu, C.C.; Morley, T.J.; Carroll, V.M.; Papin, C.; Gouasmat, A.; Alagille, D.; Tamagnan, G.; Koike, T. Design, synthesis, and evaluation of (2-Aminocyclopropyl)phenyl derivatives as novel positron emission tomography imaging agents for lysine-specific demethylase 1 in the brain. J. Med. Chem.,  2021, 64(7), 3780-3793.
 [http://dx.doi.org/10.1021/acs.jmedchem.0c01937] [PMID: 33729758]
Cite As
Current Medicinal Chemistry

A Quinquennial Review of Potent LSD1 Inhibitors Explored for the Treatment of Different Cancers, with Special Focus on SAR Studies

Abstract
