61. Kakizawa T, Mizukami T, Itoh Y, Hasegawa M, Sasaki R, Suzuki T (2016) Evaluation of
phenylcyclopropylamine compounds by enzymatic assay of lysine-specific demethylase 2 in the
presence of NPAC peptide. Bioorg Med Chem Lett 26:1193–1195
62. Sugino N, Kawahara M, Tatsumi G, Kanai A, Matsui H, Yamamoto R, Nagai Y, Fujii S,
Shimazu Y, Hishizawa M, Inaba T, Andoh A, Suzuki T, Takaori-Kondo A (2017) A novel
LSD1 inhibitor NCD38 ameliorates MDS-related leukemia with complex karyotype by attenuating leukemia programs via activating super-enhancers. Leukemia 31:2303–2314
63. Rao S, Zafar A (2014) Methods and compositions comprising lysine-specific demethylase
inhibitors (LSD) for inhibiting growth of cancer stem cells. Patent Appl WO2014205511A1
64. Sareddy GR, Viswanadhapalli S, Surapaneni P, Suzuki T, Brenner A, Vadlamudi RK (2017)
Novel KDM1A inhibitors induce differentiation and apoptosis of glioma stem cells via unfolded
protein response pathway. Oncogene 36:2423–2434
65. Mohammad HP, Smitheman KN, Kamat CD, Soong D, Federowicz KE, van Aller GS, Schneck
JL, Carson JD, Liu Y, Butticello M, Bonnette WG, Gorman SA, Degenhardt Y, Bai Y, McCabe
MT, Pappalardi MB, Kasparec J, Tian X, McNulty KC, Rouse M, McDevitt P, Ho T,
Crouthamel M, Hart TK, Concha NO, McHugh CF, Miller WH, Dhanak D, Tummino PJ,
Carpenter CL, Johnson NW, Hann CL, Kruger RG (2015) A DNA hypomethylation signature
predicts antitumor activity of LSD1 inhibitors in SCLC. Cancer Cell 28:57–69
66. Maes T, Mascaró C, Ortega A, Lunardi S, Ciceri F, Somervaille TC, Buesa C (2015) KDM1
histone lysine demethylases as targets for treatments of oncological and neurodegenerative
disease. Epigenomics 7:609–626
67. Vianello P, Botrugno OA, Cappa A, Dal Zuffo R, Dessanti P, Mai A, Marrocco B, Mattevi A,
Meroni G, Minucci S, Stazi G, Thaler F, Trifiró P, Valente S, Villa M, Varasi M, Mercurio C
(2016) Discovery of a novel inhibitor of histone lysine-specific demethylase 1A (KDM1A/
LSD1) as orally active antitumor agent. J Med Chem 59:1501–1517
68. Rotili D, Tomassi S, Conte M, Benedetti R, Tortorici M, Ciossani G, Valente S, Marrocco B,
Labella D, Novellino E, Mattevi A, Altucci L, Tumber A, Yapp C, King ON, Hopkinson RJ,
Kawamura A, Schofield CJ, Mai A (2014) Pan-histone demethylase inhibitors simultaneously
targeting Jumonji C and lysine-specific demethylases display high anticancer activities. J Med
Chem 57:42–55
69. Ota Y, Itoh Y, Kaise A, Ohta K, Endo Y, Masuda M, Sowa Y, Sakai T, Suzuki T (2016)
Targeting cancer with PCPA-drug conjugates: LSD1 inhibition-triggered release of
4-hydroxytamoxifen. Angew Chem Int Ed 55:16115–16118
70. Schmitt ML, Hauser AT, Carlino L, Pippel M, Schulz-Fincke J, Metzger E, Willmann D, Yiu T,
Barton M, Schüle R, Sippl W, Jung M (2013) Nonpeptidic propargylamines as inhibitors of
lysine specific demethylase 1 (LSD1) with cellular activity. J Med Chem 56:7334–7342
71. Lee MG, Wynder C, Schmidt DM, McCafferty DG, Shiekhattar R (2006) Histone H3 lysine
4 demethylation is a target of nonselective antidepressive medications. Chem Biol 13:563–567
72. Culhane JC, Wang D, Yen PM, Cole PA (2010) Comparative analysis of small molecules and
histone substrate analogues as LSD1 lysine demethylase inhibitors. J Am Chem Soc
132:3164–3176
73. Prusevich P, Kalin JH, Ming SA, Basso M, Givens J, Li X, Hu J, Taylor MS, Cieniewicz AM,
Hsiao PY, Huang R, Roberson H, Adejola N, Avery LB, Casero RA Jr, Taverna SD, Qian J,
Tackett AJ, Ratan RR, McDonald OG, Feinberg AP, Cole PA (2014) A selective phenelzine
analogue inhibitor of histone demethylase LSD1. ACS Chem Biol 9:1284–1293
74. Hazeldine S, Pachaiyappan B, Steinbergs N, Nowotarski S, Hanson AS, Casero RA Jr, Woster
PM (2012) Low molecular weight amidoximes that act as potent inhibitors of lysine-specific
demethylase 1. J Med Chem 55:7378–7391
75. Wu F, Zhou C, Yao Y, Wei L, Feng Z, Deng L, Song Y (2016) 3-(Piperidin-4-ylmethoxy)
pyridine containing compounds are potent inhibitors of lysine specific demethylase 1. J Med
Chem 59:253–263
76. Sorna V, Theisen ER, Stephens B, Warner SL, Bearss DJ, Vankayalapati H, Sharma S (2013)
High-throughput virtual screening identifies novel N
0 -(1-phenylethylidene)-benzohydrazides as
potent, specific, and reversible LSD1 inhibitors. J Med Chem 56:9496–9508
218
T. Suzuki
phenylcyclopropylamine compounds by enzymatic assay of lysine-specific demethylase 2 in the
presence of NPAC peptide. Bioorg Med Chem Lett 26:1193–1195
62. Sugino N, Kawahara M, Tatsumi G, Kanai A, Matsui H, Yamamoto R, Nagai Y, Fujii S,
Shimazu Y, Hishizawa M, Inaba T, Andoh A, Suzuki T, Takaori-Kondo A (2017) A novel
LSD1 inhibitor NCD38 ameliorates MDS-related leukemia with complex karyotype by attenuating leukemia programs via activating super-enhancers. Leukemia 31:2303–2314
63. Rao S, Zafar A (2014) Methods and compositions comprising lysine-specific demethylase
inhibitors (LSD) for inhibiting growth of cancer stem cells. Patent Appl WO2014205511A1
64. Sareddy GR, Viswanadhapalli S, Surapaneni P, Suzuki T, Brenner A, Vadlamudi RK (2017)
Novel KDM1A inhibitors induce differentiation and apoptosis of glioma stem cells via unfolded
protein response pathway. Oncogene 36:2423–2434
65. Mohammad HP, Smitheman KN, Kamat CD, Soong D, Federowicz KE, van Aller GS, Schneck
JL, Carson JD, Liu Y, Butticello M, Bonnette WG, Gorman SA, Degenhardt Y, Bai Y, McCabe
MT, Pappalardi MB, Kasparec J, Tian X, McNulty KC, Rouse M, McDevitt P, Ho T,
Crouthamel M, Hart TK, Concha NO, McHugh CF, Miller WH, Dhanak D, Tummino PJ,
Carpenter CL, Johnson NW, Hann CL, Kruger RG (2015) A DNA hypomethylation signature
predicts antitumor activity of LSD1 inhibitors in SCLC. Cancer Cell 28:57–69
66. Maes T, Mascaró C, Ortega A, Lunardi S, Ciceri F, Somervaille TC, Buesa C (2015) KDM1
histone lysine demethylases as targets for treatments of oncological and neurodegenerative
disease. Epigenomics 7:609–626
67. Vianello P, Botrugno OA, Cappa A, Dal Zuffo R, Dessanti P, Mai A, Marrocco B, Mattevi A,
Meroni G, Minucci S, Stazi G, Thaler F, Trifiró P, Valente S, Villa M, Varasi M, Mercurio C
(2016) Discovery of a novel inhibitor of histone lysine-specific demethylase 1A (KDM1A/
LSD1) as orally active antitumor agent. J Med Chem 59:1501–1517
68. Rotili D, Tomassi S, Conte M, Benedetti R, Tortorici M, Ciossani G, Valente S, Marrocco B,
Labella D, Novellino E, Mattevi A, Altucci L, Tumber A, Yapp C, King ON, Hopkinson RJ,
Kawamura A, Schofield CJ, Mai A (2014) Pan-histone demethylase inhibitors simultaneously
targeting Jumonji C and lysine-specific demethylases display high anticancer activities. J Med
Chem 57:42–55
69. Ota Y, Itoh Y, Kaise A, Ohta K, Endo Y, Masuda M, Sowa Y, Sakai T, Suzuki T (2016)
Targeting cancer with PCPA-drug conjugates: LSD1 inhibition-triggered release of
4-hydroxytamoxifen. Angew Chem Int Ed 55:16115–16118
70. Schmitt ML, Hauser AT, Carlino L, Pippel M, Schulz-Fincke J, Metzger E, Willmann D, Yiu T,
Barton M, Schüle R, Sippl W, Jung M (2013) Nonpeptidic propargylamines as inhibitors of
lysine specific demethylase 1 (LSD1) with cellular activity. J Med Chem 56:7334–7342
71. Lee MG, Wynder C, Schmidt DM, McCafferty DG, Shiekhattar R (2006) Histone H3 lysine
4 demethylation is a target of nonselective antidepressive medications. Chem Biol 13:563–567
72. Culhane JC, Wang D, Yen PM, Cole PA (2010) Comparative analysis of small molecules and
histone substrate analogues as LSD1 lysine demethylase inhibitors. J Am Chem Soc
132:3164–3176
73. Prusevich P, Kalin JH, Ming SA, Basso M, Givens J, Li X, Hu J, Taylor MS, Cieniewicz AM,
Hsiao PY, Huang R, Roberson H, Adejola N, Avery LB, Casero RA Jr, Taverna SD, Qian J,
Tackett AJ, Ratan RR, McDonald OG, Feinberg AP, Cole PA (2014) A selective phenelzine
analogue inhibitor of histone demethylase LSD1. ACS Chem Biol 9:1284–1293
74. Hazeldine S, Pachaiyappan B, Steinbergs N, Nowotarski S, Hanson AS, Casero RA Jr, Woster
PM (2012) Low molecular weight amidoximes that act as potent inhibitors of lysine-specific
demethylase 1. J Med Chem 55:7378–7391
75. Wu F, Zhou C, Yao Y, Wei L, Feng Z, Deng L, Song Y (2016) 3-(Piperidin-4-ylmethoxy)
pyridine containing compounds are potent inhibitors of lysine specific demethylase 1. J Med
Chem 59:253–263
76. Sorna V, Theisen ER, Stephens B, Warner SL, Bearss DJ, Vankayalapati H, Sharma S (2013)
High-throughput virtual screening identifies novel N
0 -(1-phenylethylidene)-benzohydrazides as
potent, specific, and reversible LSD1 inhibitors. J Med Chem 56:9496–9508
218
T. Suzuki