Development of myeloperoxidase inhibitors to treat atherosclerosis

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$274,434.00
Award Year:
2009
Program:
SBIR
Phase:
Phase I
Contract:
1R43HL095251-01A1
Award Id:
93949
Agency Tracking Number:
HL095251
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
TORREY PINES PHARMACEUTICALS, INC., 449 PINE NEEDLES DR, DEL MAR, CA, 92014
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
809869840
Principal Investigator:
RICHARD MAKI
() -
Business Contact:
RICHARD MAKI
() -
Research Institution:
n/a
Abstract
DESCRIPTION (provided by applicant): The overall objective of the proposed research is to develop an orally active inhibitor of MPO as a treatment for acute and chronic diseases. MPO is an abundant enzyme in leukocytes and its expression can be induced in macrophages at inflammatory sites such as atherosclerotic lesions. MPO catalyzes a reaction between chloride and hydrogen peroxide to generate hypochlorous acid, a strong oxidizing agent. Multiple lines of evidence implicate MPO in the initiation and progr ession of atherosclerosis through oxidation of lipoproteins, impairment of reverse cholesterol transport, and reduction of bioavailable NO. A small molecule inhibitor of MPO may be an important component in a list of therapeutic options for the treatment o f chronic inflammatory diseases including atherosclerosis. In Specific Aim 1 we propose to screen a small molecule library for inhibitors of MPO. In Specific Aim 2 we propose to test the small molecule inhibitors in a variety of secondary assays designed f or selectivity and cellular function before testing the small molecule in an in vivo model of atherosclerosis. PUBLIC HEALTH RELEVANCE: Myeloperoxidase is recognized as an important causative contributory agent in inflammatory diseases including atheroscle rosis. An inhibitor of myeloperoxidase would provide a novel therapeutic agent that could be used as an adjunct therapy to statins and other therapeutics already on the market. The experiments outlined in this Phase I SBIR application will help set the sta ge for the development of a novel and safe myeloperoxidase inhibitor.

* information listed above is at the time of submission.

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