# Project 3: Targeting MYC in CRC

> **NIH NIH P50** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $327,594

## Abstract

PROJECT SUMMARY/ABSTRACT: P3. Targeting MYC
Recurring genetic perturbations in colorectal cancer (CRC) activate MYC, an oncogenic transcription factor
that features prominently in human cancer. Despite the pervasive involvement of MYC in CRC, and a wealth of
studies demonstrating that genetic inhibition of MYC promotes frank tumor regression in mouse model
systems, MYC is generally considered undruggable. Indeed, there are currently no drug-like molecules
capable of directly blocking MYC function in cancer cells. Recently, however, we presented a new paradigm for
target gene recognition by MYC that also created a new opportunity to discover drugs that block MYC function.
We found that the stable association of MYC with chromatin depends on its direct interaction with the
chromatin scaffolding protein WDR5, which co-localizes broadly with MYC across the genome and facilitates
MYC binding to target genes. Structural analysis revealed that MYC binds WDR5 by engaging a shallow,
hydrophobic cleft on the surface of WDR5 that is well-suited for drug discovery. The goal of this project is to
target the MYC–WDR5 interface to discover a drug that will disable MYC function in CRC by preventing the
stable association of MYC with target gene chromatin. This project combines drug discovery, structural biology,
medicinal chemistry, biochemistry, and cutting-edge genomic approaches, along with powerful model systems,
to identify, refine, and validate drug-like molecules that disrupt the MYC-WDR5 interaction, and to explore their
effectiveness as anti-cancer agents against CRC. Within the five year funding period, we intend to produce
first-in-class MYC–WDR5 inhibitors that will be fully validated for their utility in treating CRC and ready to
proceed to Investigational New Drug (IND)-enabling studies. Successful completion of this project will address
a clear unmet clinical need for targeted anti-MYC therapies, which are expected to have broad efficacy against
CRCs for which there are only limited treatment options. Drugs discovered in this program will likely also have
utility against a wide spectrum of cancer types.

## Key facts

- **NIH application ID:** 9975137
- **Project number:** 5P50CA236733-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Robert Daniel Beauchamp
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $327,594
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975137

## Citation

> US National Institutes of Health, RePORTER application 9975137, Project 3: Targeting MYC in CRC (5P50CA236733-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9975137. Licensed CC0.

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