Identification of New Therapeutic Agents Using Novel
Variants of p53 Tumor Suppression Protein

Inventor: Thanos Halazonetis

Tech ID: HT-96001, HT-95001, HT-98001, HT-9436

Description: Inactivation of the p53 tumor suppressor protein, by mutation or by viruses, has been identified in over one-half of all human tumors. The inactivated protein usually has reduced DNA-binding capacity, which renders it ineffective in regulating cell division and cell growth. Delivery of the p53 gene to tumor cells has led to the elimination of the tumor in both animal models and some early clinical studies.

Given the limitations of gene therapy and effective targeting of gene delivery, small molecules that enhance p53-DNA binding would have considerable potential as cancer therapeutics. However, the low melting temperature of wild-type p53 has been a major technical obstacle to developing drug screening assays to identify compounds that enhance p53-DNA binding. Wistar researchers have developed a new p53 protein construct that increases the p53 melting temperature by 16oC. This engineered p53 protein can be used to monitor changes in sequence-specific binding of p53 to DNA and the effects of p53 mutants on this interaction.

Key Words: Therapeutic, screening, cancer, target

Applications and Advantages: Wistar's p53 variants are useful for screening assays to identify potential cancer therapeutics that will increase the binding of p53 to DNA and thus inactivate the effects of mutant p53.

Intellectual Property Status: U.S. and international patents are pending.

Licensing Opportunity: Wistar is seeking sponsored research support and collaborations for the use of these variants to screen for cancer therapeutic agents.

Contact:

Meryle J. Melnicoff
Director, Business Development
The Wistar Institute
3601 Spruce Street
Philadelphia, PA 19104
Phone: (215) 898-0049
Fax: (215) 573-2456
melnicoff@wistar.org

Last Updated: Nov. 99