Jump to main content
Jump to site search

Issue 31, 2018
Previous Article Next Article

Antibody drug conjugates (ADCs) charged with HDAC inhibitor for targeted epigenetic modulation

Author affiliations

Abstract

We describe here two novel antibody-drug conjugates loaded with the HDAC inhibitor ST7612AA1 (IC50 equal to 0.07 μM on NCI-H460 cells), a thiol-based molecule with a moderate toxicity in vivo. Two payloads were prepared using cleavable and non-cleavable linkers. After anchoring to cetuximab through amide bond with lysines, the resulting HDAC inhibitor-antibody conjugates showed ability to recognize EGFR and efficient internalization in tumor cells. Both ADCs induced sensible increment of histones 3 and 4 and alpha-tubulin acetylation. Animal models of human solid tumors showed high anti-tumor efficacy of the conjugates without the toxicity generally observed with traditional ADCs delivering highly potent cytotoxic drugs. These compounds, the first ADCs charged with not highly cytotoxic warheads, are potentially suitable for epigenetic modulation, extending the ADC strategy to the targeted delivery of HDAC inhibitors with many possible therapeutic applications beyond cancer.

Graphical abstract: Antibody drug conjugates (ADCs) charged with HDAC inhibitor for targeted epigenetic modulation

Back to tab navigation

Supplementary files

Article information


Submitted
12 Dec 2017
Accepted
26 Jun 2018
First published
03 Jul 2018

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2018,9, 6490-6496
Article type
Edge Article

Antibody drug conjugates (ADCs) charged with HDAC inhibitor for targeted epigenetic modulation

E. Cini, V. Faltoni, E. Petricci, M. Taddei, L. Salvini, G. Giannini, L. Vesci, F. M. Milazzo, A. M. Anastasi, G. Battistuzzi and R. De Santis, Chem. Sci., 2018, 9, 6490
DOI: 10.1039/C7SC05266A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

Reproduced material should be attributed as follows:

  • For reproduction of material from NJC:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
  • For reproduction of material from PCCP:
    [Original citation] - Published by the PCCP Owner Societies.
  • For reproduction of material from PPS:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
  • For reproduction of material from all other RSC journals:
    [Original citation] - Published by The Royal Society of Chemistry.

Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.


Social activity

Search articles by author

Spotlight

Advertisements