# Small Molecule MYC Degraders as Novel Cancer Therapeutic Agents

> **NIH NIH R44** · STEMSYNERGY THERAPEUTICS, INC. · 2024 · $1,060,173

## Abstract

PROJECT SUMMARY/ABSTRACT
The MYC family proteins are comprised of three paralogs termed c-myc, N-myc, and L-myc. The MYC proteins
play a fundamental role in cell proliferation and oncogenesis by regulating cellular processes such as gene
transcription, protein translation, cell cycle progression, and cell death. While N-myc and L-myc drive
oncogenesis in a small number of cancer types, the requirement of c-myc is widespread in a broad range of
human cancers. MYC protein levels are highly regulated by Aurora A: both c-myc and N-myc bind to Aurora
kinase A to “escape” proteasomal degradation. With the support of SBIR Phase I, we have successfully identified
novel small molecules that 1). directly target the MYC:Aurora A binding interface, 2). potently degrade both
endogenous N-myc and c-myc (henceforth “MYC degraders”), 3). are metabolically stable and orally
bioavailable, and 4). are efficacious in inhibiting the growth of tumors dependent on either N-myc or c-myc.
For the SBIR Phase II period, we plan to advance pre-clinical development of our MYC degraders with an
emphasis on treating c-myc-dependent cancers. We propose two specific aims:
Specific Aim 1: Test the efficacy of SSTA-315 across c-myc dependent cancers, while in parallel develop
derivative c-myc degraders with improved potency and efficacy.
Specific Aim 2: Evaluate the safety profile of SSTA-315 (or an alternative lead MYC degrader) in IND-enabling
GLP toxicity studies.
Successful completion of the proposed studies will complete IND-enabling safety studies for our lead MYC
degrader, preparing for the IND registration with the FDA as the immediate next step. Given that MYC proteins
are deregulated in most human cancers, our MYC degraders have potential to impact the lives of millions of
cancer patients in U.S. and represent a significant market opportunity.

## Key facts

- **NIH application ID:** 10933575
- **Project number:** 5R44CA268456-03
- **Recipient organization:** STEMSYNERGY THERAPEUTICS, INC.
- **Principal Investigator:** Dennis Liang Fei
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,060,173
- **Award type:** 5
- **Project period:** 2022-04-05 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10933575

## Citation

> US National Institutes of Health, RePORTER application 10933575, Small Molecule MYC Degraders as Novel Cancer Therapeutic Agents (5R44CA268456-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10933575. Licensed CC0.

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