Medicinal Chemistry Insights in the Discovery of Novel LSD1 Inhibitors

References

• Helin K , DhanakD . Chromatin proteins and modifications as drug targets . Nature502 ( 7472 ), 480 – 488 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Fan J , KrautkramerKA , FeldmanJLet al. Metabolic regulation of histone post-translational modifications . ACS Chem. Biol.10 ( 1 ), 95 – 108 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Suzuki T , MiyataN . Lysine demethylases inhibitors . J. Med. Chem.54 ( 24 ), 8236 – 8250 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Thinnes CC , EnglandKS , KawamuraAet al. Targeting histone lysine demethylases – progress, challenges, and the future . Biochim. Biophys. Acta1839 ( 12 ), 1416 – 1432 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Zheng YC , MaJ , WangZet al. A systematic review of histone lysine-specific demethylase 1 and its inhibitors . Med. Res. Rev. doi:10.1002/med.21350 ( 2015 ) ( Epub ahead of print ).
   PubMed Web of Science ®Google Scholar
• McGrath J , TrojerP . Targeting histone lysine methylation in cancer . Pharmacol. Ther.150 , 1 – 22 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• H⊘jfeldt JW , AggerK , HelinK . Histone lysine demethylases as targets for anticancer therapy . Nat. Rev. Drug Discov.12 ( 12 ), 917 – 930 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Mould DP , McGonagleAE , WisemanDHet al. Reversible inhibitors of LSD1 as therapeutic agents in acute myeloid leukemia: clinical significance and progress to date . Med. Res. Rev.35 ( 3 ), 586 – 618 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Varier RA , TimmersHT . Histone lysine methylation and demethylation pathways in cancer . Biochim. Biophys. Acta1815 ( 1 ), 75 – 89 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Hayami S , KellyJD , ChoHSet al. Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers . Int. J. Cancer.128 ( 3 ), 574 – 586 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Amente S , LaniaL , MajelloB . The histone LSD1 demethylase in stemness and cancer transcription programs . Biochim. Biophys. Acta1829 ( 10 ), 981 – 986 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Chen C , GeJ , LuQet al. Expression of Lysine-specific demethylase 1 in human epithelial ovarian cancer . J. Ovarian. Res.8 ( 1 ), 28 ( 2015 ).
   PubMedGoogle Scholar
• Chen L , XuY , XuBet al. Over-expression of lysine-specific demethylase 1 predicts tumor progression and poor prognosis in human esophageal cancer . Int. J. Clin. Exp. Pathol.7 ( 12 ), 8929 – 8934 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Niebel D , KirfelJ , JanzenVet al. Lysine-specific demethylase 1 (LSD1) in hematopoietic and lymphoid neoplasms . Blood124 ( 1 ), 151 – 152 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Lv T , YuanD , MiaoXet al. Over-expression of LSD1 promotes proliferation, migration and invasion in non-small cell lung cancer . PLoS ONE7 ( 4 ), e35065 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Hoshino I , AkutsuY , MurakamiKet al. Histone demethylase LSD1 inhibitors prevent cell growth by regulating gene expression in esophageal squamous cell carcinoma cells . Ann. Surg. Oncol. ( 2015 ) ( Epub ahead of print ).
   PubMed Web of Science ®Google Scholar
• Crea F , SunL , MaiAet al. The emerging role of histone lysine demethylases in prostate cancer . Mol. Cancer.11 , 52 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Sakamoto A , HinoS , NagaokaKet al. Lysine demethylase LSD1 coordinates glycolytic and mitochondrial metabolism in hepatocellular carcinoma cells . Cancer Res.75 ( 7 ), 1445 – 1456 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Hino S , SakamotoA , NagaokaKet al. FAD-dependent lysine-specific demethylase-1 regulates cellular energy expenditure . Nat. Commun.3 , 758 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Zhang F , XuD , YuanLet al. Epigenetic regulation of Atrophin1 by lysine-specific demethylase 1 is required for cortical progenitor maintenance . Nat. Commun.5 , 5815 ( 2012 ).
   Web of Science ®Google Scholar
• Whyte WA , BilodeauS , OrlandoDAet al. Enhancer decommissioning by LSD1 during embryonic stem cell differentiation . Nature482 , 221 – 225 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Duteil D , MetzgerE , WillmannDet al. LSD1 promotes oxidative metabolism of white adipose tissue . Nat. Commun.5 , 4093 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Abdulla A , ZhangY , HsuFNet al. Regulation of lipogenic gene expression by lysine-specific histone demethylase-1 (LSD1) . J. Biol. Chem.289 , 29937 – 29947 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Pan D , MaoC , WangYX . Suppression of gluconeogenic gene expression by LSD1-mediated histone demethylation . PLoS ONE8 , e66294 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Cai C , HeHH , GaoSet al. Lysine-specific demethylase 1 has dual functions as a major regulator of androgen receptor transcriptional activity . Cell Rep.9 ( 5 ), 1618 – 1627 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Wu CY , HsiehCY , HuangKEet al. Cryptotanshinone down-regulates androgen receptor signaling by modulating lysine-specific demethylase 1 function . Int. J. Cancer131 ( 6 ), 1423 – 1434 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Bennani-Baiti IM . Integration of ERα-PELP1-HER2 signaling by LSD1 (KDM1A/AOF2) offers combinatorial therapeutic opportunities to circumventing hormone resistance in breast cancer . Breast Cancer Res.14 , 112 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Cortez V , MannM , TekmalSet al. Targeting the PELP1-KDM1 axis as a potential therapeutic strategy for breast cancer . Breast Cancer Res.14 ( 4 ), R108 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Pollock JA , LarreaMD , JasperJSet al. Lysine-specific histone demethylase 1 inhibitors control breast cancer proliferation in ERα-dependent and -independent manners . ACS Chem. Biol.7 ( 7 ), 1221 – 1231 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Laurent B , RuituL , MurnJet al. A specific LSD1/KDM1A isoform regulates neuronal differentiation through H3K9 demethylation . Mol. Cell.57 ( 6 ), 957 – 970 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Shin J , MingGL , SongH . Molecular toggle switch of histone demethylase LSD1 . Mol. Cell.57 ( 6 ), 949 – 950 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Han X , GuiB , XiongCet al. Destabilizing LSD1 by Jade-2 promotes neurogenesis: an antibraking system in neural development . Mol. Cell.55 ( 3 ), 482 –4 94 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Li A , HeY , SunSet al. Lysine-specific demethylase 1 inhibitors protect cochlear spiral ganglion neurons against cisplatin-induced damage . Neuroreport26 ( 9 ), 539 – 547 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Liang Y , QuenelleD , VogelJLet al. A novel selective LSD1/KDM1A inhibitor epigenetically blocks herpes simplex virus lytic replication and reactivation from latency . mBio4 ( 1 ), e00558 – e005512 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Bag P , OjhaD , MukherjeeHet al. A dihydro-pyrido-indole potently inhibits HSV-1 infection by interfering the viral immediate early transcriptional events . Antiviral Res.105 , 126 – 134 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Robertson JC , HurleyNC , TortoriciMet al. Expanding the druggable space of the LSD1/CoREST epigenetic target: new potential binding regions for drug-like molecules, peptides, protein partners, and chromatin . PLoS Comput. Biol.9 ( 7 ), e1003158 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Luka Z , MossF , LoukachevitchLVet al. Histone demethylase LSD1 is a folate-binding protein . Biochemistry50 ( 21 ), 4750 – 4756 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Luka Z , PakhomovaS , LoukachevitchLVet al. Crystal structure of the histone lysine specific demethylase LSD1 complexed with tetrahydrofolate . Protein Sci.23 ( 7 ), 993 – 998 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Khan MN , SuzukiT , MiyataN . An overview of phenylcyclopropylamine derivatives: biochemical and biological significance and recent developments . Med. Res. Rev.33 ( 4 ), 873 – 910 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Vianello P , BotrugnoOA , CappaAet al. Synthesis, biological activity and mechanistic insights of 1-substituted cyclopropylamine derivatives: a novel class of irreversible inhibitors of histone demethylase KDM1A . Eur. J. Med. Chem.86 , 352 – 363 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Pieroni M , AnnunziatoG , AzzaliEet al. Further insights into the SAR of α-substituted cyclopropylamine derivatives as inhibitors of histone demethylase KDM1A . Eur. J. Med. Chem.92 , 377 – 386 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Valente S , RodriguezV , MercurioCet al. Pure enantiomers of benzoylamino-tranylcypromine: LSD1 inhibition, gene modulation in human leukemia cells and effects on clonogenic potential of murine promyelocytic blasts . Eur. J. Med. Chem.94 , 163 – 174 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Valente S , RodriguezV , MercurioCet al. Pure diastereomers of a tranylcypromine-based LSD1 inhibitor: enzyme selectivity and in-cell studies . ACS Med. Chem. Lett.6 ( 2 ), 173 – 177 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Mohammad H , SmithemanK , CusanMet al. Inhibition of LSD1 as a therapeutic strategy for the treatment of acute myeloid leukemia . Blood122 ( 21 ), 3964 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Kruger RG . Novel anti-tumor activity of targeted LSD1 inhibition . Presented at : Proceedings of the 105th Annual Meeting of the American Association for Cancer Research . San Diego, CA, USA , 5–9 April (2014) .
   Google Scholar
• Neelamegam R , RicqEL , MalvaezMet al. Brain-penetrant LSD1 inhibitors can block memory consolidation . ACS Chem. Neurosci.3 ( 2 ), 120 – 128 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Rivers A , VaitkusK , RuizMAet al. RN-1, a potent and selective LSD1 inhibitor, increases γ-globin expression, f-retics, and f-cells in a sickle cell disease mouse model . Exp. Hematol.43 ( 7 ), 546 – 553 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Fang Z , SongY , ZhanPet al. Conformational restriction: an effective tactic in ‘follow-on’-based drug discovery . Future Med. Chem.6 ( 8 ), 885 – 901 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Rodriguez V , ValenteS , RovidaSet al. Pyrrole- and indole- containing tranylcypromine derivatives as novel lysine-specific demethylase 1 inhibitors active on cancer cells . Med. Chem. Commun.6 , 665 – 670 ( 2014 ).
   Google Scholar
• Zhan P , SongY , ItohYet al. Recent advances in the structure-based rational design of TNKSIs . Mol. Biosyst.10 ( 11 ), 2783 – 2799 ( 2014 ).
   PubMedGoogle Scholar
• Kang D , SongY , ChenWet al. ’Old dogs with new tricks’: exploiting alternative mechanisms of action and new drug design strategies for clinically validated HIV targets . Mol. Biosyst.10 ( 8 ), 1998 – 2022 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Ueda R , SuzukiT , MinoKet al. Identification of cell-active lysine specific demethylase 1-selective inhibitors . J. Am. Chem. Soc.131 ( 48 ), 17536 –1753 7 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Etani T , SuzukiT , NaikiTet al. NCL1, a highly selective lysine-specific demethylase 1 inhibitor, suppresses prostate cancer without adverse effect . Oncotarget6 ( 5 ), 2865 – 2878 ( 2015 ).
   PubMedGoogle Scholar
• Pajtler KW , WeingartenC , ThorTet al. The KDM1A histone demethylase is a promising new target for the epigenetic therapy of medulloblastoma . Acta Neuropathol. Commun.1 ( 1 ), 19 ( 2013 ).
   PubMedGoogle Scholar
• Guibourt N , OrtegaMA , Castro-PalominoLJ : WO2010043721 ( 2010 ).
   Google Scholar
• Khan MNA , TsumotoH , ItohYet al. Design, synthesis, and biological activity of N-alkylated analogue of NCL1, a selective inhibitor of lysine-specific demethylase 1 . Med. Chem. Commun.6 , 407 – 412 ( 2015 ).
   Google Scholar
• Kumarasinghe IR , WosterPM . Synthesis and evaluation of novel cyclic peptide inhibitors of lysine-specific demethylase 1 . ACS Med. Chem. Lett.5 ( 1 ), 29 – 33 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Tortorici M , BorrelloMT , TardugnoMet al. Protein recognition by short peptide reversible inhibitors of the chromatin-modifying LSD1/CoREST lysine demethylase . ACS Chem. Biol.8 ( 8 ), 1677 – 82 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Kakizawa T , OtaY , ItohYet al. Histone H3 peptide based LSD1-selective inhibitors . Bioorg. Med. Chem. Lett.25 ( 9 ), 1925 – 1928 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Ogasawara D , ItohY , TsumotoHet al. Lysine-specific demethylase 1-selective inactivators: protein-targeted drug delivery mechanism . Angew. Chem. Int. Ed. Engl.52 ( 33 ), 8620 – 8624 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Itoh Y , OgasawaraD , OtaYet al. Synthesis, LSD1 inhibitory activity, and LSD1 binding model of optically pure lysine-PCPA conjugates . Comput. Struct. Biotechnol. J.9 , e201402002 ( 2014 ).
   PubMedGoogle Scholar
• Zhan P , LiuX . Rationally designed multitarget anti-HIV agents . Curr. Med. Chem.20 ( 13 ), 1743 – 58 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Zhan P , LiuX . Designed multiple ligands: an emerging anti-HIV drug discovery paradigm . Curr. Pharm. Des.15 ( 16 ), 1893 – 917 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Han H , YangX , PandiyanKet al. Synergistic re-activation of epigenetically silenced genes by combinatorial inhibition of DNMTs and LSD1 in cancer cells . PLoS ONE8 ( 9 ), e75136 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Huang Y , StewartTM , WuYet al. Novel oligoamine analogues inhibit lysine-specific demethylase 1 and induce reexpression of epigenetically silenced genes . Clin. Cancer Res.15 , 7217 – 7228 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Vasilatos SN , KatzTA , OesterreichSet al. Crosstalk between lysine-specific demethylase 1 (LSD1) and histone deacetylases mediates antineoplastic efficacy of HDAC inhibitors in human breast cancer cells . Carcinogenesis34 ( 6 ), 1196 – 1207 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Singh MM , JohnsonB , VenkatarayanAet al. Preclinical activity of combined HDAC and KDM1A inhibition in glioblastoma . Neuro Oncol.17 ( 11 ), 1463 – 1473 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Wissmann M , YinN , MüllerJMet al. Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression . Nat. Cell Biol.9 ( 3 ), 347 – 353 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Song Y , XuH , ChenWet al. 8-Hydroxyquinoline: a privileged structure with broad-ranging pharmacological potentials . Med. Chem. Commun.6 , 61 – 74 ( 2015 ).
   Web of Science ®Google Scholar
• Rotili D , TomassiS , ConteMet al. Pan-histone demethylase inhibitors simultaneously targeting Jumonji C and lysine-specific demethylases display high anticancer activities . J. Med. Chem.57 , 42 – 55 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Schmitt ML , HauserAT , CarlinoLet al. Nonpeptidic propargylamines as inhibitors of lysine specific demethylase 1 (LSD1) with cellular activity . J. Med. Chem.56 ( 18 ), 7334 – 7342 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Wang J , LuF , RenQet al. Novel histone demethylase LSD1 inhibitors selectively target cancer cells with pluripotent stem cell properties . Cancer Res.71 ( 23 ), 7238 – 7249 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Hsu HC , LiuYS , TsengKCet al. CBB1003, a lysine-specific demethylase 1 inhibitor, suppresses colorectal cancer cells growth through down-regulation of leucine-rich repeat-containing G-protein-coupled receptor 5 expression . J. Cancer Res. Clin. Oncol.141 ( 1 ), 11 – 21 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Prusevich P , KalinJH , MingSAet al. A selective phenelzine analogue inhibitor of histone demethylase LSD1 . ACS Chem. Biol.9 ( 6 ), 1284 – 1293 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Sorna V , TheisenER , StephensBet al. High-throughput virtual screening identifies novel N’;-(1-phenylethylidene)-benzohydrazides as potent, specific, and reversible LSD1 inhibitors . J. Med. Chem.56 ( 23 ), 9496 – 9508 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Theisen ER , GajiwalaS , BearssJet al. Reversible inhibition of lysine specific demethylase 1 is a novel anti-tumor strategy for poorly differentiated endometrial carcinoma . BMC Cancer14 , 752 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Fiskus W , SharmaS , ShahBet al. Highly effective combination of LSD1 (KDM1A) antagonist and pan-histone deacetylase inhibitor against human AML cells . Leukemia28 ( 11 ), 2155 – 2164 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Zhou Y , LiY , WangWet al. Synthesis and biological evaluation of novel (E)-N’-(2, 3-dihydro-1H-inden-1-ylidene) benzohydrazides as potent LSD1 inhibitors . Bioorg. Med. Chem. Lett. doi:10.1016/j.bmcl.2015.06.054 ( 2015 ).
   Google Scholar
• Hazeldine S , PachaiyappanB , SteinbergsNet al. Low molecular weight amidoximes that act as potent inhibitors of lysine-specific demethylase 1 . J. Med. Chem.55 ( 17 ), 7378 – 7391 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Zheng YC , DuanYC , MaJLet al. Triazole-dithiocarbamate based selective lysine specific demethylase 1 (LSD1) inactivators inhibit gastric cancer cell growth, invasion, and migration . J. Med. Chem.56 ( 21 ), 8543 – 8560 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Ye XW , ZhengYC , DuanYCet al. Synthesis and biological evaluation of coumarin-1, 2, 3-triazole-dithiocarbamate hybrids as potent LSD1 inhibitors . Med. Chem. Commun.5 , 650 – 654 ( 2014 ).
   Google Scholar
• Ma LY , ZhengYC , WangSQet al. Design, synthesis, and structure-activity relationship of novel LSD1 inhibitors based on pyrimidine-thiourea hybrids as potent, orally active antitumor agents . J. Med. Chem.58 ( 4 ), 1705 – 1716 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Dulla B , KirlaKT , RathoreVet al. Synthesis and evaluation of 3-amino/guanidine substituted phenyl oxazoles as a novel class of LSD1 inhibitors with anti-proliferative properties . Org. Biomol. Chem.11 ( 19 ), 3103 – 3107 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Kutz CJ , HolshouserSL , MarrowEAet al. 3,5-Diamino-1,2,4-triazoles as a novel scaffold for potent, reversible LSD1 (KDM1A) inhibitors . Med. Chem. Commun.5 ( 12 ), 1863 – 1870 ( 2014 ).
   Google Scholar
• Kutz CJ , HolshouserSL , WosterPM . Small molecule epigenetic modulators for the treatment of cardiovascular disorders . Presented at : Abstracts of Papers, 249th ACS National Meeting and Exposition . CO, USA , 22–26 March (2015) .
   Google Scholar
• Newman DJ , CraggGM . Natural products as sources of new drugs over the 30 years from 1981 to 2010 . J. Nat. Prod.75 ( 3 ), 311 – 335 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Newman DJ , CraggGM . Natural products as sources of new drugs over the last 25 years . J. Nat. Prod.70 ( 3 ), 461 – 477 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Newman DJ , CraggGM , SnaderKM . Natural products as sources of new drugs over the period 1981–2002 . J. Nat. Prod.66 ( 7 ), 1022 – 1037 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Abdulla A , ZhaoX , YangF . Natural polyphenols inhibit lysine-specific demethylase-1 in vitro . J. Biochem. Pharmacol. Res.1 ( 1 ), 56 – 63 ( 2013 ).
   PubMedGoogle Scholar
• Huang Y , GreeneE , Murray StewartTet al. Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes . Proc. Natl Acad. Sci. USA104 , 8023 – 8028 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Zhu Q , HuangY , MartonLJet al. Polyamine analogs modulate gene expression by inhibiting lysine-specific demethylase 1 (LSD1) and altering chromatin structure in human breast cancer cells . Amino Acids42 , 887 – 898 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Murray-Stewart T , WosterPM , CaseroRAJr . The re-expression of the epigenetically silenced e-cadherin gene by a polyamine analogue lysine-specific demethylase-1 (LSD1) inhibitor in human acute myeloid leukemia cell lines . Amino Acids46 , 585 – 594 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Müller G . Medicinal chemistry of target family-directed masterkeys . Drug Discov. Today.8 ( 15 ), 681 – 691 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Song Y , ChenW , KangDet al. ’Old friends in new guise’: exploiting privileged structures for scaffold re-evolution/refining . Comb. Chem. High Throughput Screen.17 ( 6 ), 536 – 553 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Bauer RA . Covalent inhibitors in drug discovery: from accidental discoveries to avoided liabilities and designed therapies . Drug Discov. Today20 ( 9 ), 1061 – 1073 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Kim SA , ChatterjeeN , JenningsMJet al. Extranucleosomal DNA enhances the activity of the LSD1/CoREST histone demethylase complex . Nucleic Acids Res.43 ( 10 ), 4868 – 4880 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Zhan P , ItohY , SuzukiTet al. Strategies for the discovery of target-specific or isoform-selective modulators . J. Med. Chem. doi:10.1021/acs.jmedchem.5b00229 ( 2015 ).
   Google Scholar
• Lolli M , NarramoreS , FishwickCWet al. Refining the chemical toolbox to be fit for educational and practical purpose for drug discovery in the 21st Century . Drug Discov. Today doi:10.1016/j.drudis.2015.04.010 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Zhao F , LiuN , ZhanPet al. Repurposing of HDAC inhibitors towards anti-HCV drug discovery: how to teach old dog new tricks? Future Med. Chem. 7 ( 11 ), 1367 – 1371 ( 2015 ).
   PubMed Web of Science ®Google Scholar