rvx-208 and Dyslipidemias

Dyslipidaemia is a major risk factor for cardiovascular diseases. Pharmacological lowering of LDL-C levels using statins reduces cardiovascular risk. However, a substantial residual risk persists especially in patients with type 2 diabetes mellitus. Because of the inverse association observed in epidemiological studies of HDL-C with the risk for cardiovascular diseases, novel therapeutic strategies to raise HDL-C levels or improve HDL functionality are developed as complementary therapy for cardiovascular diseases. However, until now most therapies targeting HDL-C levels failed in clinical trials because of side effects or absence of clinical benefits. This chapter will highlight the emerging small molecules currently developed and tested in clinical trials to pharmacologically modulate HDL-C and functionality including new CETP inhibitors (anacetrapib, evacetrapib), novel PPAR agonists (K-877, CER-002, DSP-8658, INT131 and GFT505), LXR agonists (ATI-111, LXR-623, XL-652) and RVX-208.

Topics: Animals; Cardiovascular Diseases; Cholesterol Ester Transfer Proteins; Drug Design; Dyslipidemias; Humans; Hypolipidemic Agents; Liver X Receptors; Molecular Targeted Therapy; Orphan Nuclear Receptors; Peroxisome Proliferator-Activated Receptors; Quinazolines; Quinazolinones; Signal Transduction

Reduction in low-density lipoprotein cholesterol (LDL-C) levels has been associated with a 25-30% reduction in cardiovascular disease risk. However, there still remains a significant and quantifiable risk. Since epidemiologic data have demonstrated that low levels of high-density lipoprotein cholesterol (HDL-C) are associated with an increased risk for cardiovascular disease, novel therapeutic agents are currently being developed to either raise HDL-C levels or enhance HDL functionality. This review will highlight some of these therapeutic agents including cholesteryl ester transfer protein inhibitors, apolipoprotein A-I mimetics, RVX-208, and apolipoprotein A-I based infusion therapies. For each therapeutic class, an overview of the mechanism of action, pharmacokinetic data, and efficacy/safety evidence will be provided.

Topics: Animals; Apolipoprotein A-I; Biomarkers; Cardiovascular Diseases; Cholesterol Ester Transfer Proteins; Cholesterol, HDL; Cholesterol, LDL; Dyslipidemias; Humans; Hypolipidemic Agents; Molecular Mimicry; Quinazolines; Quinazolinones; Treatment Outcome