. 2021 Apr 6;13(7):1746. doi: 10.3390/cancers13071746

Table 2.

Current epigenetic drugs in the treatment of myeloid malignancies.

Targets/Agents	Characteristics/Mechanisms of Action
Azanucleosides [100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127]	Promote differentiation, activate the innate immune response and lead to DNA damage response causing cytotoxicity.
	Through incorporation into RNA, AZA also reduces protein synthesis and impairs DNA synthesis and repair.
	Azacitidine and decitabine are FDA-approved for the treatment of MDS.
	Oral azacitidine CC-486 FDA approved as maintenance therapy in AML.
BET [128,129,130,131,132,133,134,135,136,137,138,139,140]	Mainly BRD4 inhibitors.
	Reduce expression of oncogenes, including MYC and BCL2, thus lead to reduced proliferation and increased apoptosis.
	In clinical trials, modest efficacy and adverse effects suggesting their use in combinatorial therapy.
HDAC [141,142,143,144,145,146]	Inhibitors restore histone acetylation, promoting differentiation and apoptosis.
HDAC [141,142,143,144,145,146]	Often have dual roles making their use as monotherapies difficult.
IDH1/IDH2 [147,148,149,150,151,152,153,154,155,156,157]	IDH inhibitors reduce the total serum 2-HG level and induce AML cell differentiation.
IDH1/IDH2 [147,148,149,150,151,152,153,154,155,156,157]	IDH1 inhibitor Ivosidenib and IDH2 inhibitor enasidenib are FDA approved for the treatment of adult relapsed or refractory AML with IDH1 or IDH2 mutations, respectively.
EZH2 [158,159,160]	S-adenosyl methionine-competitive EZH2 inhibitor tazemetostat is FDA approved for the treatment of epithelioid sarcoma.
DOT1L [160,161,162,163,164,165]	DOT1L inhibitor pinometostat selectively kills MLL-rearranged AML cells and is in phase I clinical trial in patients with MLL translocation.
DOT1L [160,161,162,163,164,165]	Pinometostat has limited pharmacokinetics (requires continuous intravenous administration); thus, new DOT1L inhibitors are currently being assessed in vitro and in PDX models.
PRMT5 [166,167,168,169,170]	PRMT5 inhibition has anti-leukemic effects in AML due to the downregulation of FLT3 expression.
PRMT5 [166,167,168,169,170]	PRMT5 inhibition induces alternative splicing and downregulation of proteins required for proliferation.
LSD1 [171,172,173,174,175,176,177]	LSD1 inhibition abrogates the clonogenic potential and induces differentiation of MLL-rearranged AML as well as sensitizes AML cells to differentiation induced by all-trans-retinoic acid.