Small molecule n-MYC degraders as novel cancer therapeutic agents
Ended Project Grant Awarded Last action
- Award ID
- R43CA268456
- Recipient
-
Stemsynergy Therapeutics Inc. UEI WVEMHJFUNJ97
- Awarding agency
-
National Cancer Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $799,998
Award facts
- Assistance listing
- 93.395 Cancer Treatment Research
- Completion date
- Place of performance
- Franklin, TN 37067, USA
Award details come from USAspending.gov.
Description
- 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.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $399,999 | |
| Original award | $399,999 |
Quick answers
Who received award R43CA268456?
R43CA268456 was awarded to Stemsynergy Therapeutics Inc. by National Cancer Institute (National Institutes of Health) on April 5, 2022.
How much is award R43CA268456 worth?
$799,998 has been obligated on R43CA268456.
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