Discovering HDL-elevating drugs: are there simplistic approaches to a polygenic disorder?
Pape, M.E.; Bisgaier, C.L.
Idrugs the Investigational Drugs Journal 1(4): 442-451
1998
ISSN/ISBN: 1369-7056 PMID: 18465577 Document Number: 486259
High density lipoproteins (HDL) are thought to serve a protective role in the development of atherosclerosis. For this reason, there have been intensive efforts over the years to discover and develop compounds that would successfully elevate HDL levels in humans. However, unlike the HMG-CoA reductase inhibitors, which lower low density lipoproteins (LDL), there has been a dearth of compounds specifically indicated for HDL elevation which have progressed significantly through drug development. Nonetheless, recent research into the mechanism of action of HDL elevators in preclinical animal models has provided some valuable insights for targeted strategies. In this review, these strategies are discussed: firstly data are described on the known effects of these compounds in animal models and at the cellular and molecular level; secondly, a working hypothesis for identifying and testing putative HDL-elevating drugs is provided; and finally, the future roles of genomics, transcriptomics and proteomics in HDL drug discovery research will be discussed.