Antibody drug conjugates with hydroxamic acid cargos for histone deacetylase (HDAC) inhibition

Chem Commun (Camb). 2021 Jan 28;57(7):867-870. doi: 10.1039/d0cc06131j.

Abstract

Antitumor hydroxamates SAHA and Dacinostat have been linked to cetuximab and trastuzumab through a non-cleavable linker based on the p-mercaptobenzyl alcohol structure. These antibody drug conjugates (ADCs) were able to inhibit HDAC in several tumour cell lines. The cetuximab based ADCs block human lung adenocarcinoma cell proliferation, demonstrating that bioconjugation with antibodies is a suitable approach for targeted therapy based on hydroxamic acid-containing drugs. This work also shows that ADC-based delivery might be used to overcome the classical pharmacokinetic problems of hydroxamic acids.

MeSH terms

  • A549 Cells
  • Cell Proliferation / drug effects
  • Cetuximab / chemistry
  • Histone Deacetylase Inhibitors / chemistry*
  • Histone Deacetylase Inhibitors / metabolism
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism*
  • Humans
  • Hydroxamic Acids / chemistry*
  • Hydroxamic Acids / metabolism
  • Hydroxamic Acids / pharmacology
  • Immunoconjugates / chemistry*
  • Immunoconjugates / metabolism
  • Trastuzumab / chemistry

Substances

  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Immunoconjugates
  • Histone Deacetylases
  • Trastuzumab
  • Cetuximab