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DNA Repair Enzymes As Cancer Targets

Background:
The National Cancer Institute's Laboratory of Molecular Pharmacology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize inhibitors of human tyrosyl-DNA phosphodiesterase (Tdp1) as cancer targets.

Technology:
Tyrosyl-DNA phosphodiesterase (Tdp1) is an enzyme that repairs topoisomerase I (Top1)-mediated DNA damage induced by chemotherapeutic agents and DNA lesions that interfere with transcription and replication.  Because of its role in repairing Top1- mediated DNA damage and damage associated with DNA strand breaks, Tdp1 is a relevant target for anticancer therapies.  Tdp1 inhibitors are expected to can have selective activity toward tumor tissues when used in combination with Top1 inhibitors. 

This invention describes Me-3, 4 dephostatin, which the inventors have described as a specific Tdp1 inhibitor.  Me-3, 4 dephostatin, and protein-tyrosine phosphatase inhibitors in general, could potentiate the pharmacological action of Top1 inhibitors currently used in cancer treatment.  Additionally, Tdp1 inhibitors may exhibit antitumor activity by themselves because tumors have excess free radicals.

Further R&D Needed:  Screen more Me-3, 4 derivatives and optimize lead compound for therapeutic development

R&D Status: Pre-clinical development

IP Status:  U.S. Provisional Application No. 61,040,203 filed 28 March 2008

Value Proposition:

• Tdp1 inhibitors as relevant targets for anticancer therapies

• Ability to use Tdp1 inhibitors to potentiate the pharmacological action of existing cancer treatments.