Design of Novel Molecules that Modify the Activity of the Transcriptional Coactivator p300/CBP

Inventor: Ronen Marmorstein, Xin Liu, Philip Cole, Ling Wang

Tech ID: MR07002

Description: Researchers at The Wistar Institute and The Johns Hopkins University have characterized the structure of the histone acetyltransferase (HAT) domain of the p300/CBP transcriptional coactivator. p300/CBP is highly-conserved and is critical for regulating the transcription of a wide range of eukaryotic genes through its HAT activity. It has been implicated in a number of disease pathways, including cancer, cardiac disease, diabetes, and HIV pathogenesis. Mutations in the protein have been linked to a variety of tumors, including pancreatic cancer and acute leukemias. Wistar researchers have determined the structure of a complex substrate binding site, and have identified a number of key residues that contribute to the chemistry of acetyl transfer by p300/CBP. This scaffold should form a template for designing more specific compounds that are capable of modifying the HAT activity of this transcriptional coactivator.  

Key Words: p300/CBP, histone acetyltransferase, cardiac disease, HIV, diabetes mellitus, cancer therapy, rational drug design

Applications and Advantages: A method for designing, screening, and testing drugs that target the HAT domain of the p300/CBP transcriptional coactivator, using in silico or in vitro methods, is provided. Wistar researchers have found that while the p300 HAT domain is similar to other HAT structures, it possesses several unique structural characteristics. Regulators of p300/CBP could be useful in cancer therapy, treatment of HIV, or a variety of metabolic diseases. These compounds could also be used to augment or correct the effects of mutations associated with diseases such as acute leukemia.

Intellectual Property Status: This technology is protected by a provisional patent application.

Licensing Opportunity: Wistar is seeking to collaborate with a corporate partner to use this technology to develop small molecule modulators of p300/CBP. An exclusive license or sponsored research to further develop the technology would be considered.

Contact:

Meryle J. Melnicoff
Director, Business Development
The Wistar Institute
3601 Spruce Street
Room 322
Philadelphia, PA 19104
Phone: (215) 898-0049
Fax: (215) ) 495-6861
melnicoff@wistar.org

Last Updated: Jan-08