Luminescence complementation technology for the identification of MYC:TRRAP inhibitors

Area of Science:

• Oncology
• Molecular Biology
• Drug Discovery

Background:

• Targeted therapies are revolutionizing cancer treatment, yet novel strategies are needed for cancers with dysregulated transcriptional programs.
• The MYC oncogene is frequently amplified and overexpressed in human cancers, driving tumor growth and survival.
• Cancer cells often exhibit "MYC addiction," making MYC a promising therapeutic target.

Purpose of the Study:

• To develop a novel strategy for inhibiting MYC function by disrupting its interaction with TRRAP using small molecules.
• To establish a luminescence complementation assay for identifying MYC:TRRAP interaction inhibitors.
• To validate the developed assay by assessing disruptions in TRRAP binding.

Main Methods:

• Development of a luminescence complementation platform to screen for small molecules inhibiting the MYC:TRRAP interaction.
• Engineering of MYC constructs with substitutions in the MYC homology 2 region.
• Measurement of TRRAP binding disruption to validate the assay's efficacy.

Main Results:

• Successful development of a luminescence complementation assay for MYC:TRRAP interaction inhibition screening.
• Demonstrated assay validation by measuring the impact of MYC mutations on TRRAP binding.
• Established a foundation for identifying novel small molecules targeting MYC function.

Conclusions:

• The developed assay provides a robust platform for discovering MYC-specific targeted therapies.
• Disrupting the MYC:TRRAP interaction is a viable strategy for inhibiting MYC function in cancer.
• This research opens new avenues for developing treatments for MYC-driven cancers.