Small molecule inhibitors of TET enzymes for cancer therapy

IP Status: Utility Patent Pending; Application No. 18/633,908

Applications

• Research tools for epigenetic studies
• Therapeutic agents for various cancers

Key Benefits & Differentiators

• Highly potent: Compounds inhibit TET enzyme activity with low micromolar concentrations.
• Unique bifunctional design: Mimicry of both the native substrate and co-factor molecules enhances potency and selectivity compared to existing inhibitors.

Technology Overview

Epigenetic modifications, such as DNA methylation, play a critical role in regulating gene expression and are often dysregulated in various cancers. Ten-eleven translocation (TET) enzymes are key players in this process, as they remove the most abundant DNA methylation mark, 5-Methylcytosine (5mC). TET expression and activity are frequently dysregulated in cancers like chronic lymphocytic leukemia, acute myeloid leukemia, and triple-negative breast cancer, making them promising therapeutic targets. However, the lack of potent and selective small-molecule inhibitors has limited the exploration of TETs as therapeutic targets.

Researchers at the University of Minnesota have developed a new series of bifunctional, cytosine-based chemical scaffolds designed to inhibit TET enzyme activity. This novel architecture represents a significant improvement over other inhibitors by mimicking both the native substrate and co-factor molecules that TET enzymes recognize. This unique bifunctional strategy enhances both potency and selectivity, addressing the shortcomings of current inhibitors which have suboptimal potency and potential off-target effects. The technology includes two sets of compounds: an "active" form for in vitro enzymatic assays and a "prodrug" version for cellular administration, which is expected to have the most therapeutic relevance for various cancer indications.

Phase of Development

TRL: 3
The technology is in the early research stage, with initial in vitro and cellular assays completed and a modular synthesis methodology developed.

Desired Partnerships

This technology is now available for:

• License
• Sponsored research
• Co-development

Please contact our office to share your business’ needs and learn more.

Researchers

• Natalia Tretyakova, PhD Professor, Department of Medicinal Chemistry