44. Andrisani OM (2013) Deregulation of epigenetic mechanisms by the hepatitis B virus X protein
in hepatocarcinogenesis. Viruses 5:858–872
45. Xu J, Bauer DE, Kerenyi MA, Vo TD, Hou S, Hsu YJ, Yao H, Trowbridge JJ, Mandel G, Orkin
SH (2013) Corepressor-dependent silencing of fetal hemoglobin expression by BCL11A. Proc
Natl Acad Sci U S A 110:6518–6523
46. Cui S, Kolodziej KE, Obara N, Amaral-Psarris A, Demmers J, Shi L, Engel JD, Grosveld F,
Strouboulis J, Tanabe O (2011) Nuclear receptors TR2 and TR4 recruit multiple epigenetic
transcriptional corepressors that associate specifically with the embryonic β-type globin promoters in differentiated adult erythroid cells. Mol Cell Biol 31:3298–3311
47. Shi L, Cui S, Engel JD, Tanabe O (2013) Lysine-specific demethylase 1 is a therapeutic target
for fetal hemoglobin induction. Nat Med 19:291–294
48. Hino S, Sakamoto A, Nagaoka K, Anan K, Wang Y, Mimasu S, Umehara T, Yokoyama S,
Kosai K, Nakao M (2012) FAD-dependent lysine-specific demethylase-1 regulates cellular
energy expenditure. Nat Commun 3:758
49. Buesa C, Mascaró C, Rotllant D, Griñan-Ferré C, Pallàs M, Maes T (2015) The dual LSD1/
MAOB inhibitor ORY2001 prevents the development of the memory deficit in SAMP8 mice
through induction of neuronal plasticity and reduction of neuroinflammation. Alzheimers
Dement 11:P905
50. Rusconi F, Grillo B, Ponzoni L, Bassani S, Toffolo E, Paganini L, Mallei A, Braida D,
Passafaro M, Popoli M, Sala M, Battaglioli E (2016) LSD1 modulates stress-evoked transcription of immediate early genes and emotional behavior. Proc Natl Acad Sci U S A
113:3651–3656
51. Schmidt DM, McCafferty DG (2007) trans-2-Phenylcyclopropylamine is a mechanism-based
inactivator of the histone demethylase LSD1. Biochemistry 46:4408–4416
52. Yang M, Culhane JC, Szewczuk LM, Jalili P, Ball HL, Machius M, Cole PA, Yu H (2007)
Structural basis for the inhibition of the LSD1 histone demethylase by the antidepressant trans2-phenylcyclopropylamine. Biochemistry 46:8058–8065
53. Kauffman EC, Robinson BD, Downes MJ, Powell LG, Lee MM, Scherr DS, Gudas LJ, Mongan
NP (2011) Role of androgen receptor and associated lysine-demethylase coregulators, LSD1
and JMJD2A, in localized and advanced human bladder cancer. Mol Carcinog 50:931–944
54. Schenk T, Chen WC, Göllner S, Howell L, Jin L, Hebestreit K, Klein HU, Popescu AC,
Burnett A, Mills K, Casero RA Jr, Marton L, Woster P, Minden MD, Dugas M, Wang JC, Dick
JE, Müller-Tidow C, Petrie K, Zelent A (2012) Inhibition of the LSD1 (KDM1A) demethylase
reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia. Nat
Med 18:605–611
55. Tsutsumi T, Iwao K, Hayashi H, Kirihara T, Kawaji T, Inoue T, Hino S, Nakao M, Tanihara H
(2016) Potential neuroprotective effects of an LSD1 inhibitor in retinal ganglion cells via p38
MAPK activity. Invest Ophthalmol Vis Sci 57:6461–6473
56. Ueda R, Suzuki T, Mino K, Tsumoto H, Nakagawa H, Hasegawa M, Sasaki R, Mizukami T,
Miyata N (2009) Identification of cell-active lysine specific demethylase 1-selective inhibitors.
J Am Chem Soc 131:17536–17537
57. Son SY, Ma J, Kondou Y, Yoshimura M, Yamashita E, Tsukihara T (2008) Structure of human
monoamine oxidase A at 2.2-Å resolution: the control of opening the entry for substrates/
inhibitors. Proc Natl Acad Sci U S A 105:5739–5744
58. Binda C, Li M, Hubalek F, Restelli N, Edmondson DE, Mattevi A (2003) Insights into the mode
of inhibition of human mitochondrial monoamine oxidase B from high-resolution crystal
structures. Proc Natl Acad Sci U S A 100:9750–9755
59. Etani T, Suzuki T, Naiki T, Naiki-Ito A, Ando R, Iida K, Kawai N, Tozawa K, Miyata N,
Kohri K, Takahashi S (2015) NCL1, a highly selective lysine-specific demethylase 1 inhibitor,
suppresses prostate cancer without adverse effect. Oncotarget 6:2865–2878
60. Ogasawara D, Itoh Y, Tsumoto H, Kakizawa T, Mino K, Fukuhara K, Nakagawa H,
Hasegawa M, Sasaki R, Mizukami T, Miyata N, Suzuki T (2013) Lysine-specific demethylase
1-selective inactivators: protein-targeted drug delivery mechanism. Angew Chem Int Ed
52:8620–8624
Lysine-Specific Histone Demethylases 1/2 (LSD1/2) and Their Inhibitors
217
in hepatocarcinogenesis. Viruses 5:858–872
45. Xu J, Bauer DE, Kerenyi MA, Vo TD, Hou S, Hsu YJ, Yao H, Trowbridge JJ, Mandel G, Orkin
SH (2013) Corepressor-dependent silencing of fetal hemoglobin expression by BCL11A. Proc
Natl Acad Sci U S A 110:6518–6523
46. Cui S, Kolodziej KE, Obara N, Amaral-Psarris A, Demmers J, Shi L, Engel JD, Grosveld F,
Strouboulis J, Tanabe O (2011) Nuclear receptors TR2 and TR4 recruit multiple epigenetic
transcriptional corepressors that associate specifically with the embryonic β-type globin promoters in differentiated adult erythroid cells. Mol Cell Biol 31:3298–3311
47. Shi L, Cui S, Engel JD, Tanabe O (2013) Lysine-specific demethylase 1 is a therapeutic target
for fetal hemoglobin induction. Nat Med 19:291–294
48. Hino S, Sakamoto A, Nagaoka K, Anan K, Wang Y, Mimasu S, Umehara T, Yokoyama S,
Kosai K, Nakao M (2012) FAD-dependent lysine-specific demethylase-1 regulates cellular
energy expenditure. Nat Commun 3:758
49. Buesa C, Mascaró C, Rotllant D, Griñan-Ferré C, Pallàs M, Maes T (2015) The dual LSD1/
MAOB inhibitor ORY2001 prevents the development of the memory deficit in SAMP8 mice
through induction of neuronal plasticity and reduction of neuroinflammation. Alzheimers
Dement 11:P905
50. Rusconi F, Grillo B, Ponzoni L, Bassani S, Toffolo E, Paganini L, Mallei A, Braida D,
Passafaro M, Popoli M, Sala M, Battaglioli E (2016) LSD1 modulates stress-evoked transcription of immediate early genes and emotional behavior. Proc Natl Acad Sci U S A
113:3651–3656
51. Schmidt DM, McCafferty DG (2007) trans-2-Phenylcyclopropylamine is a mechanism-based
inactivator of the histone demethylase LSD1. Biochemistry 46:4408–4416
52. Yang M, Culhane JC, Szewczuk LM, Jalili P, Ball HL, Machius M, Cole PA, Yu H (2007)
Structural basis for the inhibition of the LSD1 histone demethylase by the antidepressant trans2-phenylcyclopropylamine. Biochemistry 46:8058–8065
53. Kauffman EC, Robinson BD, Downes MJ, Powell LG, Lee MM, Scherr DS, Gudas LJ, Mongan
NP (2011) Role of androgen receptor and associated lysine-demethylase coregulators, LSD1
and JMJD2A, in localized and advanced human bladder cancer. Mol Carcinog 50:931–944
54. Schenk T, Chen WC, Göllner S, Howell L, Jin L, Hebestreit K, Klein HU, Popescu AC,
Burnett A, Mills K, Casero RA Jr, Marton L, Woster P, Minden MD, Dugas M, Wang JC, Dick
JE, Müller-Tidow C, Petrie K, Zelent A (2012) Inhibition of the LSD1 (KDM1A) demethylase
reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia. Nat
Med 18:605–611
55. Tsutsumi T, Iwao K, Hayashi H, Kirihara T, Kawaji T, Inoue T, Hino S, Nakao M, Tanihara H
(2016) Potential neuroprotective effects of an LSD1 inhibitor in retinal ganglion cells via p38
MAPK activity. Invest Ophthalmol Vis Sci 57:6461–6473
56. Ueda R, Suzuki T, Mino K, Tsumoto H, Nakagawa H, Hasegawa M, Sasaki R, Mizukami T,
Miyata N (2009) Identification of cell-active lysine specific demethylase 1-selective inhibitors.
J Am Chem Soc 131:17536–17537
57. Son SY, Ma J, Kondou Y, Yoshimura M, Yamashita E, Tsukihara T (2008) Structure of human
monoamine oxidase A at 2.2-Å resolution: the control of opening the entry for substrates/
inhibitors. Proc Natl Acad Sci U S A 105:5739–5744
58. Binda C, Li M, Hubalek F, Restelli N, Edmondson DE, Mattevi A (2003) Insights into the mode
of inhibition of human mitochondrial monoamine oxidase B from high-resolution crystal
structures. Proc Natl Acad Sci U S A 100:9750–9755
59. Etani T, Suzuki T, Naiki T, Naiki-Ito A, Ando R, Iida K, Kawai N, Tozawa K, Miyata N,
Kohri K, Takahashi S (2015) NCL1, a highly selective lysine-specific demethylase 1 inhibitor,
suppresses prostate cancer without adverse effect. Oncotarget 6:2865–2878
60. Ogasawara D, Itoh Y, Tsumoto H, Kakizawa T, Mino K, Fukuhara K, Nakagawa H,
Hasegawa M, Sasaki R, Mizukami T, Miyata N, Suzuki T (2013) Lysine-specific demethylase
1-selective inactivators: protein-targeted drug delivery mechanism. Angew Chem Int Ed
52:8620–8624
Lysine-Specific Histone Demethylases 1/2 (LSD1/2) and Their Inhibitors
217