Selective and nonselective HDAC8 inhibitors: a therapeutic patent review

Pharm Pat Anal. 2018 Nov;7(6):259-276. doi: 10.4155/ppa-2018-0019. Epub 2019 Jan 11.

Abstract

Histone deacetylase 8 (HDAC8) is one of the attractive therapeutic anticancer targets. HDAC8 has been overexpressed in a variety of human cancers. Therefore, HDAC8 inhibitors offer beneficial effects in the treatment of solid and hematological tumors. Different HDAC inhibitors entered into different phases of clinical studies. However, selectivity towards specific HDAC8 enzyme is still demanding. In this patent review, a number of patented selective and nonselective HDAC8 inhibitors along with their implication as anticancer agents have been discussed in details. Molecules should possess modified fish-like structural arrangement to impart potency and selectivity towards HDAC8. This comprehensive patent analysis will surely provide newer aspects of designing selective HDAC8 inhibitors targeted to anticancer therapy in future.

Keywords: HDAC8 inhibitors; benzamide; cancer; carboxylate; epigenetics; histone deacetylase 8; hydroxamate; selectivity; thiol.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Drug Design
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Histone Deacetylases / metabolism
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Patents as Topic
  • Repressor Proteins / antagonists & inhibitors*
  • Repressor Proteins / metabolism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Repressor Proteins
  • HDAC8 protein, human
  • Histone Deacetylases