# Small Molecule N-myc Degraders as Novel Cancer Therapeutic Agents

> **NIH NIH R43** · STEMSYNERGY THERAPEUTICS, INC. · 2022 · $399,999

## Abstract

ABSTRACT
The MYC family proteins are comprised of three paralogs termed Myc (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. High levels of N-myc protein (gene
name: MYCN) are often found in tumors of neuroendocrine origins, where it has been shown to drive tumor
growth. Amplification of the MYCN locus occurs in approximately 50% of high-risk neuroblastoma, which is the
most common extracranial solid malignancy of childhood. N-myc protein levels are highly regulated by Aurora
kinase A: N-myc binds to Aurora kinase A to “escape” proteasomal degradation. The tool small molecule Aurora
kinase A inhibitor, CD532, effectively dissociates N-myc from Aurora kinase A, resulting in N-myc protein
destabilization and regression of MYCN-amplified neuroblastomas. Although CD532 is an excellent proof-of-
concept molecule, this compound has poor solubility, limited permeability, and poor metabolic stability, making
it a poor drug candidate. To overcome these liabilities, we have developed distinct, novel small molecules, that
effectively dissociate N-myc from Aurora A and destabilize N-myc and that are more bioavailable than CD532.
For simplicity, these compounds are referred to as “N-myc degraders”.
The primary goal of our Phase I proposal is to improve the potency, selectivity, drug-like properties, and in vivo
efficacy of our lead N-myc degrader, SSTA-152. We propose two specific aims:
Specific Aim 1. Increase the potency and selectivity of SSTA-152.
Specific Aim 2. Improve drug-like properties and in vivo efficacy of SSTA-152.
The overall goal is to develop a clinical N-myc degrader for treating N-myc-driven cancers, which fulfills a
significant unmet need in patients.

## Key facts

- **NIH application ID:** 10484078
- **Project number:** 1R43CA268456-01A1
- **Recipient organization:** STEMSYNERGY THERAPEUTICS, INC.
- **Principal Investigator:** Dennis Liang Fei
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $399,999
- **Award type:** 1
- **Project period:** 2022-04-05 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10484078

## Citation

> US National Institutes of Health, RePORTER application 10484078, Small Molecule N-myc Degraders as Novel Cancer Therapeutic Agents (1R43CA268456-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10484078. Licensed CC0.

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