# Therapeutic targeting of MYC interactions with an essential cofactor

> **NIH NIH R21** · DARTMOUTH COLLEGE · 2022 · $230,010

## Abstract

MYC is the most frequently amplified gene in human cancer and is overexpressed as a
consequence of mutations in diverse oncogenic signaling pathways in 70% of cancers. Given
the ubiquity of MYC as a driver of cancer, there is a critical unmet need to develop specific
drugs that inhibit MYC function as anti-cancer therapeutics. TRansactivation/tRansformation-
domain Associated Protein (TRRAP) is an essential nuclear cofactor for MYC, and small
molecule inhibitors of the MYC:TRRAP interaction are predicted to have potent anti-cancer
activity. We developed a luciferase-based assay to identify small molecule inhibitors of
MYC:TRRAP and initiated a collaboration with the Novartis Institute for Biomedical Research to
search their non-proprietary 50,000 drug-like compound set. We identified 33 diverse
compounds that show inhibitory activity for MYC:TRRAP in the nanomolar to micromolar
concentration range using our luciferase assay. We propose to use cellular and molecular
assays to determine which of these compounds inhibit native MYC:TRRAP complexes and
ascertain their specificity regarding other MYC and/or TRRAP interacting proteins. Promising
compounds will also be assayed for growth inhibitory activity in triple negative breast cancer
cells, which have high levels of MYC and determine if growth inhibition can be attributed to loss
of MYC function. A long-term goal is the preclinical development of our top lead compounds for
in vivo experimentation.

## Key facts

- **NIH application ID:** 10512309
- **Project number:** 1R21CA267540-01A1
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** MICHAEL David COLE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $230,010
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10512309

## Citation

> US National Institutes of Health, RePORTER application 10512309, Therapeutic targeting of MYC interactions with an essential cofactor (1R21CA267540-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10512309. Licensed CC0.

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