Histone acetyltransferases: challenges in targeting bi-substrate enzymes

Clinical Epigenetics

Table 2 HAT inhibitors and activators, their target histone acetyltransferases, and proposed target pathologies

	HATs	Proposed target pathologies	References
HAT inhibitors
Bi-substrate inhibitors	Various	–	[43–45]
Garcinol	KAT3B	Breast cancer, colon carcinoma	[48, 52–54]
Curcumin	KAT3B	Cancer, inflammation, neurological disorders, cardiovascular disease, metabolic diseases^a	[47], clinicaltrials.gov
Anacardic acid	Non-selective	Sensitizing cancer cells to irradiation	[46, 51]
TH1834	KAT5	Breast cancer	[56]
Benzylidene barbituric acid	KAT3B	Cell cycle arrest, increase in hypodiploid nuclei	[57]
Isothiazolones	various	Inhibition of cancer cell proliferation	[58–61]
Thiazinesulfonamide	KAT3B	–	[62]
C646	KAT3B	Prostate cancer, melanoma, leukemia, peritoneal fibrosis	[63–68]
ICG-001	KAT3A/β-catenin	Investigation of the KAT3A/β-catenin interaction in survivin gene transcription, colon carcinoma	[70, 71]
Ischemin (bromodomain inhibitor)	KAT2A and 2B, KAT3A and 3B	Myocardial ischemia	[73]
Cyclic peptide bromodomain inhibitors		Inhibitors of the tumor suppressor protein p53	[74]
N1-aryl-propane-1,3-diamine derivatives (bromodomain inhibitors)		HIV-1	[75]
HAT activators
CTPB	KAT3B	–	[46]
TTK21	KAT3A and 3B	Neurogenesis and long-term memory, brain disease	[76]
Pentadecylidenemalonate	KAT2B	Conditioned fear, wound repair, cardiovascular disease, diabetes	[77]

^aCurcumin is currently in clinical trials for many applications as a therapeutic agent, combination therapy, or dietary supplement, although measurements on HATs or their activities were not included in the outcome parameters of these trials

ISSN: 1868-7083