TABLE 1.

DNMT versus TET inhibitors.

Group	Subgroup	Drug	Target(s)	Effect(s)	Disease(s)	References
DNMT inhibitors	Nucleoside analogs	5-azacytidine (5-AZA)	DNMT1	DNA demethylation, reactivation of TSGs, leukemic cells differentiation	MDS, AML	(Bohl et al., 2018
						Kazachenka et al. (2019)
		5-aza-2′-deoxycytidine (decitabine)		DNA demethylation, cytotoxic activities	MDS, AML	Bohl et al. (2018)
		Zebularine		DNA demethylation and tumor growth inhibition, gene reexpression	Solid tumors, MDS	Yoo et al. (2004)
		Guadecitabine (SGI-110)			Haematological and solid tumors	Griffiths et al. (2013)
		4′-thio-2′-deoxycytidine (TdCyd)			Solid tumors	Thottassery et al. (2014)
		5-fluoro-2′-deoxycytidine (FdCyd)		DNA hypomethylation, cytotoxicity	Solid tumors, AML, MDS	Beumer et al. (2008)
	Non-nucleoside analogs	Procainamide	DNMT1	DNMT1 inhibition reexpression of TSGs	Solid tumors	Lee et al. (2014)
		Procaine	DNMT1, DNMT3A	DNA demethylation, apoptosis and cell proliferation inhibition		Li et al. (2018)
		Nanaomycin A	DNMT3B	DNA hypomethylation, reactivation of silenced genes	Haematological and solid tumors (in vitro)	Moreira-Silva et al. (2020)
		Hydralazine	DNMT1	DNA demethylation, reduction of DNMT1 activity, silenced genes reexpression, cell growth inhibition	Refractory solid tumors
		MG98	DNMT1	DNMT1 downregulation, reexpression of hypermethylated genes	Solid tumors	Plummer et al. (2009)
		N-phthaloyl-l-tryptophan 1 (RG108)	DNMT1	DNA demethylation, reactivation of TSGs		Brueckner et al. (2005)
		Disulfiram	DNMT1	DNA demethylation, reactivation of silenced genes, growth inhibition	Refractory Multiple Myeloma and prostate cancer	Lin et al. (2011)
		SGI-1027	DNMT1, DNMT3A/B	Inhibition of DNMTs activity, induction of DNMT1 degradation, reactivation of TSGs, apoptosis	Haematological and solid tumors	Sun et al. (2018)
		epigallocatechin-3-gallate (EGCG)	DNMT1, DNMT3A/B	Inhibition of tumor proliferation, induction of cell death	Solid tumors	Chen et al. (2015)
TET inhibitors	Competitive inhibitors	2-Hydroxyglutarate (2-HG)	TET2	DNA hypermethylation, gene silencing, tumor progression	Haematological malignancies, AML, MDS	Ye et al. (2018)
		Fumarate	TET1/2/3	Downregulation of 5hmC levels, DNA hypermethylation		Laukka et al. (2016)
		Succinate
	α-ketoglutarate competitive substrate	Itaconate	TET2	reduction of inflammatory responses	Haematological malignancies	Chen et al. (2022)
	Non-specific inhibitor	Dimethylallyl glycine (DMOG)	TET3	Increase of 5 mC levels, downregulation of pluripotency genes	Solid tumors	Zhang et al. (2019)
	Cytosine-based inhibitor	Bobcat339	TET1/2	Inhibition of TET activity, reduction of 5hmC levels	N/A	Chua et al. (2019)
	First-in-class TET inhibitor	C35	TET1/2/3	Inhibition of TET activity, Somatic cell reprogramming	In vitro	Métivier et al. (2008)
						Singh et al. (2020)
	TET-specific inhibitor	TETi76	TET1/2/3	Reduction of 5hmC levels, growth inhibition	Haematological malignancies, MDS, AML	Guan et al. (2020)