high-density

BLT-1 is a scavenger receptor BI (SR-BI)inhibitor.

Torcetrapib (CP-529414) is a cholesteryl ester transfer protein (CETP) inhibitor designed to reduce the heterotypic transfer of cholesteryl ester from HDL to LDL and or VLDL. It failed in phase III trials due to an excess of deaths.

Bezafibrate (BM15075) is an antilipemic agent that lowers CHOLESTEROL and TRIGLYCERIDES. It decreases LOW-DENSITY LIPOPROTEINS and increases HIGH-DENSITY LIPOPROTEINS.

Gemfibrozil (CI-719) interacts with peroxisome proliferator-activated receptors (PPARalpha) resulting in PPARalpha-mediated stimulation of fatty acid oxidation and an increase in lipoprotein lipase (LPL) synthesis. Gemfibrozil is a fibric acid derivative with hypolipidemic effects. This enhances triglyceride-rich lipoprotein clearance and reduces the expression of apolipoprotein C-III (apoC-III). The reduction in hepatic production of apoC-III result in the subsequent reduction of serum levels of very-low-density-lipoprotein cholesterol (VLDL-C). In addition, gemfibrozil-mediated PPARalpha stimulation of apoA-I and apoA-II expression results in an increase in high-density lipoprotein cholesterol (HDL-C).

Sucrose-epichlorohydrin copolymer (Polysucrose 400) is a high molecular weight polymer of sucrose co-polymerized with epichlorohydrin for density gradient separation of cells, cell membranes, organelles, and viral cells and protein liqudi-liquid phase separation (LLPS).

CDD3505 (4-nitro-1-trityl-1H-imidazole) increases high-density lipoprotein cholesterol by targeting hepatic CYP3A.

CDD3506 (1-TRITYL-1H-IMIDAZOL-4-AMINE) increases high-density lipoprotein cholesterol by targeting hepatic CYP3A.

Gemcabene calcium , a first-in-class lipid-lowering agent, lowers low-density lipoprotein cholesterol (LDL-C), decreases triglycerides, and raises high-density lipoprotein cholesterol (HDL-C) andexerting anti-inflammatory activity, lowers pro-inflammatory acute-phase protein, C-reactive protein (CRP).

Gemcabene (PD-72953) is a lipid-lowering agent with anti-inflammatory activity. Gemcabene lowers low-density lipoprotein cholesterol and triglycerides, raises high-density lipoprotein cholesterol, and decreases pro-inflammatory acute-phase protein, C-reactive protei

CP-532623, a close structural analog of Torcetrapib, is a CETP inhibitor with highly lipophilic properties. It elevates high-density lipoprotein cholesterol.

PCSK9-IN-29 serves as a lipid-lowering agent that enhances the expression of low-density lipoprotein receptor (LDLR) protein and reduces PCSK9 protein expression in hepG2 cells. Additionally, in crab-eating macaques on a high-fat diet, it lowers serum LDL-C, TC, and liver enzyme ALT levels, reduces body weight and fat, and boosts bone mineral content. PCSK9-IN-29 is useful for studies involving non-alcoholic fatty liver disease and obesity.

CP 524515 is a potent inhibitor of cholesterol ester transfer protein (CETP), which results in increased levels of high-density lipoprotein cholesterol.

BLT-4 is a specific and reversible inhibitor of scavenger receptor class B type I (SR-BI). It effectively blocks the SR-BI-mediated transfer of lipids between high-density lipoprotein (HDL) and cells.

KR31173 is an AT1 antagonist with an IC50 of 3.27 nM. When labeled with the 11C isotope, KR31173 can be used as a tracer for positron emission tomography (PET). In mice, KR31173 exhibits favorable biodistribution and pharmacological characteristics. It selectively binds to organs in CD-1 mice known to have a high density of AT1 angiotensin receptors.

E-3030 free acid is a peroxisome proliferator-activated receptor (PPAR) agonist. E-3030 decreased blood glucose, triglyceride, non-esterified fatty acids, and insulin levels and increased blood adiponectin levels. Triglyceride- and non-high-density lipopr

Hyodeoxycholic acid sodium salt, a natural secondary bile acid, enhances high-density lipoprotein function, reduces farnesoid X receptor antagonist bile acids, and induces potent cytotoxicity, apoptosis, and IL-8 synthesis.

Oleic acid-2,6-diisopropylanilide is an inhibitor of acylCoA:cholesterol acyltransferase (ACAT), an intracellular cholesteryl ester synthase involved in dietary cholesterol absorption, with an IC50 of 7 nM. When administered at 0.05% to rabbits or rats on a high fat, high cholesterol diet, it reduces low-density lipoproteins and increases high-density lipoprotein levels.

Pinolenic acid is a polyunsaturated fatty acid found in Korean pine (Pinus orientalis) and maritime pine (Pinus pinaster) seed oils, which exhibit lipid-lowering properties. In transgenic mice expressing human ApoA1, a diet containing maritime pine seed oil (MPSO) reduced high-density lipoprotein and ApoA1 levels and diminished cholesterol efflux in vitro. Korean pine seed oil supplements may aid in reducing obesity by decreasing appetite, as evidenced by increased levels of satiety hormones CCK and GLP-1 and reduced desire to eat. Pinolenic acid, which is not metabolically converted to arachidonic acid, can lower arachidonic acid levels in the phosphatidylinositol fraction of HepG2 cells from 15.9% to 7.0%. The neutral, more lipophilic form of pinolenic acid is pinolenic acid ethyl ester.

Peroxisome proliferator-activated receptors (PPARs) α, δ, γ are ligand-activated nuclear transcription factors involved in the regulation of energy homeostasis as well as insulin sensitivity and glucose metabolism. Pharmacologies of PPARδ receptor agonists, though relatively obscure, have recently been reported to elevate high-density lipoprotein (HDL) cholesterol and lower plasma triglyceride (TG) levels in obese insulin resistant rhesus monkeys. CAY10592 is a full PPARδ agonist (EC50 = 30 nM) in a fatty acid oxidation assay of rat L6 muscle cells with desirable oral pharmacokinetic properties. In a transactivation assay using human PPAR receptors, CAY10592 acts as a selective partial PPARδ agonist (EC50 = 53 nM) with no effect on PPARα or PPARγ activity up to 30 μM. Chronic treatment of high fat fed ApoB100/CETP-transgenic mice with CAY10592 at a dose of 20 mg/kg increases HDL levels, decreases LDL and TG levels, and improves insulin sensitivity.

The early stage of atherosclerosis is characterized by the aggregation of foam cells, so called a fatty streak, in the inner arterial wall. CAY10487 inhibits formation of fatty streak lesions of the thoracic aorta in high cholesterol-fed rabbits without affecting plasma lipid profiles or significantly inhibiting ACAT-1 or ACAT-2 activity. The percent area occupied by the atherosclerotic lesion in rabbits supplemented with 0.05% CAY10487 in the diet was 16.1% compared to 53.5% in control rabbits. CAY10487 also exhibits antioxidant activity, inhibiting copper-mediated oxidation of low-density lipoprotein by about 75% at a concentration of 2 μM.

5(Z),11(Z),14(Z)-Eicosatrienoic acid is a polyunsaturated fatty acid found in various natural sources including maritime pine (Pinus pinaster) seed oil (MPSO), gymnospermae leaves and seeds, and freshwater gastropods. A diet containing MPSO lowered high-density lipoprotein and ApoA1 levels in transgenic mice expressing human ApoA1. MPSO was found to diminish cholesterol efflux in vitro. 5(Z),11(Z),14(Z)-Eicosatrienoic acid methyl ester, when topically applied, reduces inflammatory processes, potentially by displacing arachidonic acid from phospholipid pools and reducing downstream inflammatory products such as prostaglandin E2 and leukotrienes.

Bile acids are essential for solubilization and transport of dietary lipids, are the major products of cholesterol catabolism, and are physiological ligands for farnesoid X receptor (FXR), a nuclear receptor that regulates genes involved in lipid metabolism.1They are also inherently cytotoxic, as physiological imbalance contributes to increased oxidative stress.2,3Bile acid-controlled signaling pathways are promising novel targets to treat such metabolic diseases as obesity, type II diabetes, hyperlipidemia, and atherosclerosis.Guggulsterone, derived from resin of the guggul tree, is a competitive antagonist of FXR bothin vitroandin vivo.4Thecisstereoisomer of guggulsterone, (E)-guggulsterone, decreases chenodeoxycholic acid (CDCA)-induced FXR activation with an IC50value of 15 μM.5,6By inhibiting CDCA-induced transactivation of FXR, guggulsterone lowers low-density lipoprotein cholesterol and triglyceride levels in rodents fed a high cholesterol diet.4 1.Makishima, M., Okamoto, A.Y., Repa, J.J., et al.Identification of a nuclear receptor for bile acidsScience2841362-1365(1999) 2.Barbier, O., Torra, I.P., Sirvent, A., et al.FXR induces the UGT2B4 enzyme in hepatocytes: A potential mechanism of negative feedback control of FXR activityGastroenterology1241926-1940(2003) 3.Tan, K.P., Yang, M., and Ito, S.Activation of nuclear factor (erythroid-2 like) factor 2 by toxic bile acids provokes adaptive defense responses to enhance cell survival at the emergence of oxidative stressMol. Pharmacol.72(5)1380-1390(2007) 4.Urizar, N.L., Liverman, A.B., Dodds, D.T., et al.A natural product that lowers cholesterol as an anatagonist ligand for FXRScience296(5573)1703-1706(2002) 5.Cui, J., Huang, L., Zhao, A., et al.Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pumpThe Journal of Biological Chemisty278(12)10214-10220(2003) 6.Wu, J., Xia, C., Meier, J., et al.The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptorMolecular Endocrinology16(7)1590-1597(2002)

Palmitoleic acid is a common constituent of the triglycerides of human adipose tissue. Palmitoleic acid-based diets raise low-density lipoprotein cholesterol and diminish high-density lipoprotein cholesterol, even when dietary intake of cholesterol is maintained at a low level. Palmitelaidic acid is the trans isomer of the 16:1 fatty acid palmitoleic acid. While its effects on cholesterol levels are poorly studied, palmitelaidic acid can have very different effects from those of palmitoleic acid on lipid metabolism and mobilization. Palmitelaidic acid methyl ester is an ester version of the free acid which may be more amenable for the formulation of fatty acid-containing diets and dietary supplements.

MK-8262, an orally active and potent cholesteryl ester transfer protein (CETP) inhibitor (IC 50 = 53 nM, log D = 5.3), is a bistrifluoromethyl analogue that shows promise in research related to high-density lipoprotein (HDL) and low-density lipoprotein (LDL) with potential implications for coronary heart disease (CHD).