Zebularine, A Stable and Orally Active Inhibitor of Cytosine DNA Methyltransferase Capable of Reactivating Dormant Tumor Suppressor and Inhibiting Tumor Growth

DNA methyltransferases (also referred to as DNA methylases) transfer methyl groups from the universal methyl donor S-adenosyl methionine to specific sites on a DNA molecule. When gene sequences contain many methylated cytosines, they are less likely to be expressed. Several such 'silenced' genes are now known to be an important contributing factor in many cancers where expression of tumor suppressor genes has been suppressed. Preventing DNA methyltransferase production, or inhibiting the enzyme, may allow tumor suppressor genes that have been silenced by hypermethylation to be re-activated. Re-activation of tumor suppressor genes is intended to stop or slow tumor growth by restoring growth control mechanisms. Thus, there exists a need for an effective and stable inhibitor of DNA methylation.

The inventors have discovered a potent inhibitor of DNA methylation (Zebularine) that can specifically reactivate silenced tumor suppressor genes. This agent can be used to inhibit methylation and thereby combat certain cancers that have been linked to hypermethylation. This agent has also been shown in initial animal testing to be active orally and is more stable than some other agents in this same area of therapy and is a suitable candidate for further pre-clinical and clinical development as an anti-cancer agent to be used as monotherapy and/or as an adjunct to existing anti-cancer therapeutics.


Victor Marquez (NCI)  ➽ more inventions...

Cindy Matsen
Eric Selker

Sheldon Greer
Peter Jones

Jonathan Cheng

Intellectual Property:
U.S. Pat: 8,207,142 issued 2012-06-26
PCT Application No. PCT/US02/24223
US Application No. 60/311,435
US Application No. 60/309,242

Licensing Contact:
Lauren Nguyen-Antczak, Ph.D., J.D.
Email: lauren.nguyen-antczak@nih.gov
Phone: 301-624-8752

OTT Reference No: E-081-2001-0
Updated: Dec 1, 2016