Research Papers:

Luminescence complementation technology for the identification of MYC:TRRAP inhibitors

Edmond J. Feris, John W. Hinds and Michael D. Cole _

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Oncotarget. 2021; 12:2147-2157. https://doi.org/10.18632/oncotarget.28078

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Edmond J. Feris1,2, John W. Hinds1,2 and Michael D. Cole1,2

1 Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth College, Hanover, NH 03755, USA

2 Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA

Correspondence to:

Michael D. Cole, email: [email protected]

Keywords: cancer; drug discovery; targeted therapy; oncogene; transcription factor

Received: May 15, 2021     Accepted: September 04, 2021     Published: October 12, 2021

Copyright: © 2021 Feris et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Mechanism-based targeted therapies have exhibited remarkable success in treating otherwise untreatable or unresectable cancers. Novel targeted therapies that correct dysregulated transcriptional programs in cancer are an unmet medical need. The transcription factor MYC is the most frequently amplified gene in human cancer and is overexpressed because of mutations in an array of oncogenic signaling pathways. The fact that many cancer cells cannot survive without MYC – a phenomenon termed “MYC addiction” – provides a compelling case for the development of MYC-specific targeted therapies. We propose a new strategy to inhibit MYC function by disrupting its essential interaction with TRRAP using small molecules. To achieve our goal, we developed a platform using luminescence complementation for identifying small molecules as inhibitors of the MYC:TRRAP interaction. Here we present validation of this assay by measuring the disruption of TRRAP binding caused by substitutions to the invariant and essential MYC homology 2 region of MYC.

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