Table 3 Summary of HDAC inhibitors

Vorinostat (SAHA)

hydroxamic acid

Inhibits HDACs I & II; promotes histone acetylation, reactivates tumor suppressor genes, triggers cell cycle arrest, induces apoptosis

Anti-proliferative effects; anti-tumor efficacy

Approved for the treatment of cutaneous T-cell lymphoma (CTCL)

Gastrointestinal symptoms, fatigue, and thrombocytopenia

[88, 88,89,90,91,92,93]

Romidepsin

A cyclic peptide

Prodrug inhibits HDACs I & II, alters gene expression, and triggers cell cycle arrest, apoptosis, and autophagy, effectively preventing tumor growth and extending the survival of ATLL models

Promising in preclinical studies; moderate response rates in relapsed/refractory ATLL

Received approval to treat CTCL

Nausea, fatigue, thrombocytopenia, granulocytopenia

[94,95,96,97,98]

Belinostat

Decreases NF-κB activity, induces apoptosis, increases Tax protein levels

Enhanced cell death with AZT; reduced apoptosis with IFNα

[99]

Valproic Acid (VPA)

Augments histone acetylation active DNA demethylation; targets multiple HDACs (excluding 6 & 10), leading to the hyperacetylation of histones H3 and H4, upregulates hundreds of genes in a wide variety of cellular pathways, used in combination with AZT and IFNα to show complete molecular responses

Improved survival (chronic subtypes); cytotoxicity via induction of apoptosis and histone hyperacetylation

[100,101,102,103,104,105]

Entinostat

Benzamide

inhibits HDAC 1 and HDAC 3, demonstrating anti-tumor activity

suppresses the growth of HTLV-1-infected T-cell lines,

[106, 107]

HBI-8000 (tucidinostat)

Benzamide

Inhibits class I HDACs; inhibits tumor growth, modifies immune system, epigenetically alters cell activity

Induces cell cycle arrest and apoptosis in ATLL cell lines and patient samples who are undergoing their first round of treatment or suffer a relapse

[108, 109]