Inhibitors of Human Apurinic/apyrimidinic Endonuclease 1 (APE1), an Anticancer Drug Target
Posted Jun 30 2011 8:00pm
Description of Invention: APE1 is the primary mammalian enzyme responsible for the removal of abasic (AP sites) in DNA and functions as part of the base excision DNA repair pathway (BER). BER is instrumental in the repair of DNA damage caused by DNA alkylating agents (e.g. many cancer chemotherapeutics). APE1 has been shown to be overexpressed in cancer cells. It has been postulated that APE1 would be an attractive target in anti-cancer treatment paradigms; preclinical and clinical data confirm that APE1 is a valid anticancer drug target.
To date, only one APE1 small molecule inhibitor has progressed to clinical trials (methoxyamine hydrochloride), and this compound inhibits a wide range of repair processes, which could result in undesired side-effects. The NIH inventors now report the discovery of a novel APE1 small molecule inhibitor, which exhibits potent in vitro activity, potentiates the cytotoxicity of DNA damaging agents (alkylators methylmethane sulfonate and Temozolomide), results in the accumulation of AP sites, and has favorable pharmacokinetic properties. The inventors plan to carry out further studies in mouse tumor xenograft models.
Applications: Cancer therapeutics as single agent as well as in combination therapy.
Development Status: In vivo pharmacokinetics data on lead compounds available.
Collaborative Research Opportunity: The NIH Center for Translational Therapeutics, NHGRI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the above technology. Please contact Lili Portilla, Acting Director of Technology Transfer and Partnerships, NCTT at Lilip@nih.gov for more information.
For Licensing Information Please Contact: Betty Tong Ph.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: tongb@mail.nih.gov Phone: 301-594-6565 Fax: 301-402-0220
Description of Invention:
APE1 is the primary mammalian enzyme responsible for the removal of abasic (AP sites) in DNA and functions as part of the base excision DNA repair pathway (BER). BER is instrumental in the repair of DNA damage caused by DNA alkylating agents (e.g. many cancer chemotherapeutics). APE1 has been shown to be overexpressed in cancer cells. It has been postulated that APE1 would be an attractive target in anti-cancer treatment paradigms; preclinical and clinical data confirm that APE1 is a valid anticancer drug target.
To date, only one APE1 small molecule inhibitor has progressed to clinical trials (methoxyamine hydrochloride), and this compound inhibits a wide range of repair processes, which could result in undesired side-effects. The NIH inventors now report the discovery of a novel APE1 small molecule inhibitor, which exhibits potent in vitro activity, potentiates the cytotoxicity of DNA damaging agents (alkylators methylmethane sulfonate and Temozolomide), results in the accumulation of AP sites, and has favorable pharmacokinetic properties. The inventors plan to carry out further studies in mouse tumor xenograft models.
Applications:
Cancer therapeutics as single agent as well as in combination therapy.
Development Status:
In vivo pharmacokinetics data on lead compounds available.
Inventors:
David J Maloney (NHGRI)
Patent Status:
HHS, Reference No. E-094-2011/0
US, Application No. 61/480,145 filed 28 Apr 2011
Relevant Publication:
Licensing Status:
Available for licensing.
Collaborative Research Opportunity:
The NIH Center for Translational Therapeutics, NHGRI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the above technology. Please contact Lili Portilla, Acting Director of Technology Transfer and Partnerships, NCTT at Lilip@nih.gov for more information.
For Licensing Information Please Contact:
Betty Tong Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: tongb@mail.nih.gov
Phone: 301-594-6565
Fax: 301-402-0220
Ref No: 2277
Updated: 07/2011