TABLE 2.

Most common DNA methyltransferase inhibitors that have been approved by the FDA or are currently undergoing clinical trials for the treatment of cancer.

DNMT inhibitor	DNMT class	Maximum phase of therapy	Cancer type	Status	FDA approval	DNA damage impact: Proteins regulated or involved/pathway impact/cellular response
5-Azacitidine	Nucleoside	Phase III	Continued treatment of acute myeloid leukemia and treatment of all subtypes of myelodysplastic syndrome	Completed	Yes	Cytotoxicity caused by genomic instability and DNA damage as a result of hypomethylation; reactivation of tumor suppressor genes (TSG); apoptosis through the reduction of MCL-1 expression levels (Guo et al., 2021; Guirguis, Liddicoat, and Dawson 2020; Goel et al., 2021; Zhou, Li, and Liu 2018)
			Acute myeloid leukemia; myelodysplastic syndromes	Active, not recruiting	No
		Phase II/III	Acute myeloid leukemia or high-risk myelodysplastic syndrome	Active, not recruiting	No
		Phase II	Advanced solid tumors; male breast carcinoma; recurrent breast cancer, stage IIIC breast cancer; stage IV breast cancer, triple negative breast carcinoma; neoplasms; pancreatic cancer; epithelial ovarian cancer; advanced/metastatic non-small cell lung cancer; prostate cancer; ovarian, primary peritoneal, or fallopian tube cancer; peripheral T-cell lymphoma; Chronic myeloid leukemia; relapsed/refractory acute myeloid leukemia or relapsed/high-risk myelodysplastic syndrome	Active, not recruiting	No
		Phase I/II	Mutant myeloid neoplasm; solid tumors, gliomas; acute myeloid leukemia; myelodysplastic syndrome; non-Hodgkin lymphoma, multiple myeloma, lymphocytic leukemia; recurrent ovarian, fallopian tube or primary peritoneal cancer	Active, not recruiting	No
Decitabine (analogues: 5-Aza-fluoro-2-deoxycytidine; zebularine)	Nucleoside	Phase IV	Acute myeloid leukemia	Active, not recruiting	No	Increases DSB frequency; reduces proliferation through PARP binding; invasion and adhesion; activation of tumor suppressor genes (VHL, CDKN2A, GATA4, MLH1) Sato, et al. (2017); Dellomo et al. (2019); Kashyap et al. (2020); Nigris et al. (2021)
		Phase III	Myelodysplastic syndromes (MDS) including myelomonocytic leukemia	Completed	Yes
		Phase III	Acute myeloid leukemia; myelodysplastic syndromes	Active, not recruiting	No
		Phase II/III	Acute myeloid leukemia or high-risk myelodysplastic syndrome	Active, not recruiting	No
		Phase II	Non-small cell lung cancer; acute myeloid leukemia; leukemia; myelodysplastic syndromes	Active, not recruiting	No
		Phase I/II	Advanced solid tumors; acute myeloid leukemia; acute myelogenous leukemia; diffuse large B cell lymphoma	Active, not recruiting	No
MG98	Oligonucleotide	Phase I	Solid tumors	Completed	No	Cellular sensitization, growth inhibition concomitant with re-expression of TSGs P16ink4a and RUNX3 Beaulieu et al. (2004); Reu et al. (2004); Ramezankhani et al. (2021)
S110	Miscellaneous	Phase III	Acute myeloid leukemia; myelodysplastic syndromes, chronic myelomonocytic leukemia	Completed	No	Suggested to be a damaging variant of the NHEJ pathway through XRCC4; retards tumor growth Voorde et al. (2012); Singh et al. (2018)
		Phase II	Small cell lung cancer; myeloproliferative neoplasms; recurrent ovarian carcinoma, primary peritoneal or fallopian tube cancer; urothelial cancer; high-risk myelodysplastic syndrome	Active, not recruiting	No
		Phase I/II	Advanced kidney cancer; recurrent ovarian, fallopian tube or primary peritoneal cancer	Active, not recruiting	No

Source: U.S. National Library of Medicine, U.S. Food and Drug Administration, NIH Clinical Trial database: www.clinicaltrials.gov