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.
Contact Information:
John D. Hewes, Ph.D.
NCI Technology Transfer Center
Tel: 301-435-3121
Email: hewesj@mail.nih.gov
Please reference advertisement # 671
Revision 10/03/2008