Design of selective histone deacetylase inhibitors: rethinking classical pharmacophore. (28th June 2018)

• Record Type: Journal Article
• Authors: Melesina, Jelena; Praetorius, Lucas; Simoben, Conrad V; Robaa, Dina; Sippl, Wolfgang
• Is Part Of: Future medicinal chemistry. Volume 10:Number 13(2018)
• Page Start: 1537
• Page End: 1540
• Publication Date: 2018-06-28
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.4155/fmc-2018-0125
• Languages: English
• ISSNs: 1756-8919

Abstract

For two decades, a classical pharmacophore model comprising a zinc binding group, a linker and a cap group, has been used for the development of histone deacetylase (HDAC) inhibitors. However, some of the recently reported selective HDAC inhibitors targeting additional, usually subtype specific, cavities in the binding pocket show supplementary features which do not fit this classical pharmacophore. We, therefore, propose an extended pharmacophore model, which can describe almost all currently known HDAC inhibitors. This pharmacophore consists of six pharmacophoric features and should be helpful for the classification and design of selective HDAC inhibitors.