Novel Modulators of HDL Metabolism

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 2R44HL097438-02A1
Agency Tracking Number: R44HL097438
Amount: $1,539,615.00
Phase: Phase II
Program: SBIR
Awards Year: 2012
Solicitation Year: 2012
Solicitation Topic Code: NHLBI
Solicitation Number: PA11-096
Small Business Information
DUNS: 192526221
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (610) 400-1243
Business Contact
Phone: (610) 400-1243
Research Institution
Project Summary/Abstract Cardiovascular disease remains the leading cause of morbidity and mortality for both men and women, accounting for nearly 40% of annual deaths. High levels of LDL-C and low levels of HDL-C are well-known risk factors for heart disease. Although lowering low-density lipoprotein cholesterol (LDL-C) levels using a number of marketed drugs, of which statins are the leading drugs, has significantly reduced coronary artery disease, substantial residual cardiovascular risk remains, even with very aggressive reductions in levels of LDL-C. Accordingly, attention is now shifting toward strategies for targeting HDL-C as adjunctive therapy to prevent and treat cardiovascular disease. Many studies have emphasized that the risk factor associatedwith low levels of HDL-C is independent of that of high LDL-C. Recent epidemiological data confirmed that patients with low HDL-C level are at high risk of premature cardiovascular disease no matter how low the LDL-C level. These and other patients will dramatically benefit from an aggressive treatment of low HDL-C. The long-term goal of the proposed studies is to develop novel drugs for increasing HDL-C. Our therapeutic target is endothelial lipase (EL), a member of the lipoprotein lipase gene family thathydrolyzes HDL-C phospholipids. Recent studies demonstrated that inhibition of EL in mice results in a significant increase in HDL-C levels. In Phase I, we have identified selective inhibitors of EL and developed preliminary SAR. As part of this Phase II proposal, we plan to expand and optimize our hits, and confirm the ability of selected compounds to increase the HDL-C level using in vivo animal models.

* Information listed above is at the time of submission. *

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