Understanding fusion molecules and the A-DAC principle

Fusion molecules combine two validated anti-cancer modes of action in one molecule in order to synergise and improve upon the efficacy of the single agents. Ideally, these are chemotherapy and a targeted agent fused into one molecule.1

EDO-S101 is a representative of the A-DAC principle, and combines the active moieties of an alkylating agent and pan-histone deacetylase (HDAC) inhibitor through fusion technology.

When used in malignant cells:2

  • Alkylating agents cause breaks in the DNA that result in cell death3
  • HDAC inhibition suppresses gene transcription and prevents the growth of cancer cells and may influence control mechanisms that protect against cell death4


Rationale for development

A fusion molecule offers true bi-functionality and synergy in antineoplastic activity.5,6

The A-DAC principle was proposed to exploit a synergistic mode of action that may overcome the difficulties associated with the combined use of two separate entities.2

Successful treatment of cancer is often hindered by the development of resistance to the therapy. HDAC enzymes are overexpressed in some cancers inducing cell proliferation and resistance.2,5

To learn more about the A-DAC fusion molecule S-101 click here.

  1. Mehrling T. Future Oncology 2015;11:549-52.
  2. Mehrling and Chen. Anti-cancer Agents Med Chem 2015;16:20-8.
  3. Leoni et al. Clinical Cancer Research 2008;14:309-17.
  4. Richon VM. Br J Cancer Research 2006;95:S2-S6.
  5. National Cancer Institute. http://www.cancer.gov/publications/dictionaries/cancer-drug?expand=B. Accessed June 2016.
  6. Kraus et al. Abstract presented at ASH 56th Annual Meeting and Exposition, San Francisco, USA, 6-9 December 2014.