cholesterol synthesis

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).

Squalene (AddaVax) is a natural organic compound originally obtained for commercial purposes primarily from shark liver oil, though there are botanical sources as well, including rice bran, wheat germ, and olives. All higher organisms produce squalene, including humans. Squalene is an intermediate product in the synthesis of cholesterol and shows several pharmacological properties such as hypolipidemic, hepatoprotective, cardioprotective, antioxidant, and antitoxicant activity.

D-Pantothenic acid (vitamin B5) is a water-soluble vitamin ubiquitously found in plants and animal tissues with an antioxidant property. D-Pantothenic acid is a component of coenzyme A (CoA) and a part of the vitamin B2 complex. D-Pantothenic acid is a growth factor and is essential for various metabolic functions, including the metabolism of carbohydrates, proteins, and fatty acids. This vitamin is also involved in the synthesis of cholesterol, lipids, neurotransmitters, steroid hormones, and hemoglobin.

Lathosterol, a molecule akin to cholesterol, serves as a biomarker for the body's total cholesterol synthesis, as indicated by its serum concentration.

Cholesterol (cholesteryl alcohol) is a natural product that is the major sterol in mammals and an agonist of estrogen-related receptor α (ERRα). Cholesterol is widely found in the cell membranes of animals and is also used in the synthesis of several important hormones and bile acids.

PF-429242 is a competitive inhibitor of sterol regulatory element-binding protein (SREBP) site 1 protease (IC50 = 0.175 μM). It is selective for site 1 protease against a panel of serine proteases. PF-429242 inhibits rate of cholesterol synthesis in CHO c

U18666A is a cell-permeable drug and is a cholesterol synthesis and transport inhibitor. It inhibits replication of Ebola virus, dengue virus, and human hepatitis C virus.

Larsucosterol is a cholesterol metabolite from the nuclei of normal human liver tissues, epigenetically regulates the transcription of proteins and enzymes involved in lipid synthesis, inflammation, and apoptosis.

Simvastatin (MK 733) is an HMG-CoA reductase inhibitor (Ki=0.2 nM) with oral activity. Simvastatin has hypolipidemic activity, inhibits hepatic production of cholesterol, and is also used for the prevention of cardiovascular disease.

Lanosterol (3β-Hydroxy-8,24-lanostadiene) is a tetracyclic triterpenoid which is the compound from which all steroids are derived.

Beauveriolide I is a cyclodepsipeptide that has been found inBeauveriaand an inhibitor of lipid droplet formation.1It inhibits lipid droplet formation when used at concentrations of 3 and 10 μM, as well as inhibits cholesterol synthesis (IC50= 0.78 μM), in primary mouse peritoneal macrophages.1,2Beauveriolide I also inhibits acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in mouse macrophage membranes (IC50= 6 μM).2 1.Namatame, I., Tomoda, H., Si, S., et al.Beauveriolides, specific inhibitors of lipid droplet formation in mouse macrophages, produced by Beauveria sp. FO-6979J. Antibiot. (Tokyo)52(1)1-6(1999) 2.Namatame, I., Tomoda, H., Ishibashi, S., et al.Antiatherogenic activity of fungal beauveriolides, inhibitors of lipid droplet accumulation in macrophagesProc. Nat. Acad. Sci. USA101(3)737-742(2004)

Beauveriolide III is a cyclodepsipeptide that has been found inBeauveriaand an inhibitor of lipid droplet formation.1It inhibits lipid droplet formation when used at concentrations of 3 and 10 μM, as well as inhibits cholesterol synthesis (IC50= 0.41 μM), in primary mouse peritoneal macrophages.1,2Beauveriolide III also inhibits acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in mouse macrophage membranes (IC50= 5.5 μM).2Beauveriolide III (25 and 50 mg/kg) reduces the size of aortic atherosclerotic lesions inLdlr-/-andApoE-/-mouse models of atherosclerosis. 1.Namatame, I., Tomoda, H., Si, S., et al.Beauveriolides, specific inhibitors of lipid droplet formation in mouse macrophages, produced by Beauveria sp. FO-6979J. Antibiot. (Tokyo)52(1)1-6(1999) 2.Namatame, I., Tomoda, H., Ishibashi, S., et al.Antiatherogenic activity of fungal beauveriolides, inhibitors of lipid droplet accumulation in macrophagesProc. Nat. Acad. Sci. USA101(3)737-742(2004)

Larsucosterol sodium is a cholesterol metabolite from the nuclei of normal human liver tissues, epigenetically regulates the transcription of proteins and enzymes involved in lipid synthesis, inflammation, and apoptosis.

3-Acetyl betulinaldehyde is a triterpene and derivative of the cholesterol biosynthesis inhibitor betulin that has been found inA. japonica.1It is an intermediate in the synthesis of 3-acetylbetulinic acid, as well as various lupine and germanicane triterpenes and saponins with anticancer activity.2 1.Tung, N.H., Kwon, H.-J., Kim, J.-H., et al.An anti-influenza component of the bark of Alnus japonicaArch. Pharm. Res.33(3)363-367(2010) 2.Thibeault, D., Gauthier, C., Legault, J., et al.Synthesis and structure-activity relationship study of cytotoxic germanicane- and lupane-type 3β-O-monodesmosidic saponins starting from betulinBioorg. Med. Chem.15(18)6144-6157(2007)

Trans-Petroselinic acid, the trans isomer of petroselinic acid and an isomer of oleic acid, is detected in the milk fat of cows, goats, and ewes, as well as human breast milk. In HepG2 cells, when treated with trans-petroselinic acid (100 μM), there is an increase in the cellular content of triacylglycerols and cholesterol esters. Additionally, it upregulates the transcription of genes associated with fatty acid synthesis (SREBP-1c, ACACA, FASN, SCD1) and cholesterol synthesis (HMGCR, HMGCS1, FDFT1, SREBP-2).

28-Deoxybetulin methyleneamine is a pentacyclic triterpenoid and derivative of the cholesterol biosynthesis inhibitor betulin .1It has been used in the synthesis of triterpene derivatives with antiviral activity. 1.Nitz, T.J., Montalbetti, C., Mears, R., et al.Extended Triterpene Derivatives(2008)

Agistatin B, a mycotoxin isolated from fungus, inhibits cholesterol synthesis [1].

Bococizumab(PF-04950615) is a humanized mAb against PCSK9 and an inhibitor of the synthesis of PCSK9 in the liver that reduces the amount of low-density lipoprotein cholesterol (LDL-C) in the blood.Bococizumab is used to treat hypercholesterolemia.

Nicotinamide-d4 is intended for use as an internal standard for the quantification of nicotinamide by GC- or LC-MS. Nicotinamide is an amide form of niacin, which is also known as vitamin B3, that can be biosynthesized in vivo or obtained through the diet. It is a precursor in the synthesis of the metabolic cofactor NAD+ and an inhibitor of sirtuin 1 (SIRT1; IC50 = <50 µM). Nicotinamide (10 µM) increases the activity of serine palmitoyltransferase (SPT) and the biosynthesis of ceramide, glucosylceramide, sphingomyelin, free fatty acids, and cholesterol in primary human keratinocytes. Nicotinamide (40 µM) induces apoptosis in SNU-398, SNU-739, and HepG2 hepatocellular carcinoma (HCC) cells, and it prevents the formation of neoplastic lesions in a diethylnitrosamine-induced mouse model of HCC. Unlike niacin, nicotinamide does not reduce plasma lipid levels or induce flushing.

Uridine 5'-monophosphate disodium salt (Disodium UMP) has been used to study the effect of pyrimidine synthesis inhibitor, 5-azacytidine, on cholesterol and lipid metabolism. It has been used to study the effect of nucleotides on growth of specific intestinal bacteria.

Cholestyramine (Cholestyramine resin), a bile acid-binding resin, inhibits intestinal bile acid absorption which results in the increasing bile acid synthesis from cholesterol.

Pitavastatin-d4 Sodium Salt is a deuterated compound of Pitavastatin Sodium Salt. Pitavastatin Sodium Salt has a CAS number of 574705-92-3. Pitavastatin (NK-104) sodium is a potent hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor. Pitavastatin sodium inhibits cholesterol synthesis from acetic acid with an IC 50 of 5.8 nM in HepG2 cells. Pitavastatin sodium is an efficient hepatocyte low-density lipoprotein-cholesterol (LDL-C) receptor inducer. Pitavastatin sodium also possesses anti-atherosclerotic, anti-asthmatic, anti-osteoarthritis, antineoplastic, neuroprotective, hepatoprotective and reno-protective effects [1] [2] [3] [8].

Acaterin, an inhibitor of acyl-CoA: cholesterol acyltransferase (ACAT), inhibits synthesis of cholesteryl ester in macrophage J774.

(-)-Hydroxycitric acid (HCA) can inhibit fat synthesis and reduces food intake, the primary mechanism of action of HCA appears to be related to its ability to act as a competitive inhibitor of the enzyme ATP-citrate lyase, which catalyzes the conversion of citrate and coenzyme A to oxaloacetate and acetyl coenzyme A (acetyl-CoA), primary building blocks of fatty acid and cholesterol synthesis.

3-Hydroxybutyric acid (Butanoic acid) (or beta-hydroxybutyrate) is a ketone body. Like the other ketone bodies (acetoacetate and acetone), levels of 3-hydroxybutyrate in blood and urine are raised in ketosis. In humans, 3-hydroxybutyrate is synthesized in the liver from acetyl-CoA and can be used as an energy source by the brain when blood glucose is low. Blood levels of 3-hydroxybutyric acid levels may be monitored in diabetic patients to look for diabetic ketoacidosis. Persistent mild hyperketonemia is a common finding in newborns. Ketone bodies serve as an indispensable source of energy for extrahepatic tissues, especially the brain and lung of developing mammals. Another important function of ketone bodies is to provide acetoacetyl-CoA and acetyl-CoA for the synthesis of cholesterol, fatty acids, and complex lipids. During the early postnatal period, acetoacetate (AcAc) and beta-hydroxybutyrate are preferred over glucose as substrates for synthesis of phospholipids and sphingolipids in accord with requirements for brain growth and myelination. Thus, during the first 2 weeks of postnatal development, when the accumulation of cholesterol and phospholipids accelerates, the proportion of ketone bodies incorporated into these lipids increases. On the other hand, an increased proportion of ketone bodies is utilized for cerebroside synthesis during the period of active myelination. In the lung, AcAc serves better than glucose as a precursor for the synthesis of lung phospholipids. The synthesized lipids, particularly dipalmitoylphosphatidylcholine, are incorporated into surfactant, and thus have a potential role in supplying adequate surfactant lipids to maintain lung function during the early days of life (PMID: 3884391 ). 3-Hydroxybutyric acid is found to be associated with fumarase deficiency and medium-chain acyl-CoA dehydrogenase deficiency, which are inborn errors of metabolism.

Pitavastatin (NK-104) is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor with hypocholesterolemic and neuroprotective activities, inhibits synthesis of cholesterol from acetic acid, and reduces oxidative stress.Pitavastatin is a hepatocellular low-density lipoprotein cholesterol (LDL-C) receptor inducer, and may be used to Pitavastatin is a hepatocellular LDL-C receptor inducer and is used in the study of coronary atherosclerosis, hypercholesterolemia, and acute coronary syndromes.Pitavastatin is structurally unstable and is recommended to be formulated for immediate use.

22(S)-hydroxy Cholesterol is a synthetic oxysterol and a modulator of the liver X receptor (LXR). [1] t prevents monocyte chemoattractant protein 1 (MCP-1) expression induced by the LXR agonist GW 3965 in primary hepatocytes and downregulates mRNA expression of the LXR target genes CD36, ACSL1, and SCD-1 in human myotubes. It decreases triacylglycerol and diacylglycerol synthesis from labeled palmitate and acetate, respectively, in human myoblasts by 50% when used at a concentration of 10 uM. 22(S)-hydroxy Cholesterol also reduces fatty acid synthase (FAS) reporter activity through an LXR response element in the promoter region in COS-1 cells transfected with RXRα and LXRα and decreases the expression of MCP-1 and CCR2 in a mouse model of chronic ethanol consumption.[1] [2] Dietary supplementation of 22(S)-hydroxy cholesterol (30 mg/kg per day) leads to less body weight gain and lower liver triacylglycerol levels in rats when fed either a regular chow or high-fat diet as well as prevents an increase in plasma triacylglycerol levels resulting from a high-fat diet.[3]

Colesevelam Hydrochloride is a bile acid sequestrant with a higher affinity for glycocholic acid in vitro. Colesevelam Hydrochloride inhibits bile acid reabsorption, leading to increased bile acid synthesis and reduces cholesterol levels in patients with

Azalanstat mesylate is an anti-obesity drug acting as a lanosterol 14α-demethylase inhibitor. Azalanstat mesylate has been shown to inhibit cholesterol synthesis in HepG2 cells, human fibroblasts, hamster hepatocytes and hamster liver, by inhibiting the cytochrome P450 enzyme lanosterol 14 alpha-demethylase. When administered orally to hamsters fed regular chow, RS-21607 (50 mg/kg/day) lowered serum cholesterol in a dose-dependent manner (ED50 = 62 mg/kg) in a period of 1 week. It preferentially lowered low density lipoprotein (LDL) cholesterol and apo B relative to high density lipoprotein (HDL) cholesterol and apo A-1.

1. Homogentisic acid (2,5-dihydroxyphenylacetic acid) shows interesting antioxidant and antiradical activities, and protective effect against thermal-cholesterol degradation, comparable to those of well known antioxidants. 2. Homogentisic acid is the primary precursor of melanin synthesis in Vibrio cholerae, a Hyphomonas strain, and Shewanella colwelliana. 3. A derivative of homogentisic acid which inhibits Pfnek-1 with an IC(5) around 1.8 muM, this product is moderately active in vitro against a FcB1 P. falciparum strain (IC(5) = 12 muM).

Pitavastatin (NK-104) sodium is a potent inhibitor of hydroxymethylglutaryl-CoA (HMG-CoA) reductase and a potent inducer of the hepatocyte low-density lipoprotein cholesterol (LDL-C) receptor. pitavastatin sodium inhibits acetate synthesis of cholesterol in HepG2 cells ( Pitavastatin sodium exhibits anti-atherogenic, anti-osteoarthritic, anti-asthmatic, anti-tumour, neuroprotective, hepatoprotective and nephroprotective effects.

1. Coptisine (Coptisin) treatment increases cell viability based on its reversal effect on the enhanced activity of Indoleamine 2, 3-dioxygenase . 2. Coptisine treats myocardial I/R likely through suppressing myocardial apoptosis and inflammation by inhibiting the Rho/ROCK pathway. 3. Coptisine is a potential anti-osteosarcoma drug candidate, via exerting a strong anti-osteosarcoma effect with very low toxicity . 4. Coptisine with a high dosage could inhibit cholesterol synthesis via suppressing the HMGCR expression and promoting the use and excretion of cholesterol via up-regulating LDLR and CYP7A1 expression. 5. Coptisine suppresses adhesion, migration and invasion of MDA-MB-231 breast cancer cells in vitro, the down-regulation of MMP-9 in combination with the increase of TIMP-1 possibly contributing to the anti-metastatic function for breast cancer.

DMHCA, a potent, selective LXR agonist, specifically activates the LXR pathway's cholesterol efflux arm, avoiding triglyceride synthesis stimulation. This compound exhibits anti-inflammatory properties and is utilized in researching cholesterol homeostasis and diabetes.

D561-0775 is a direct AMPK agonist, showing potential anti-cancer activity via inducing apoptosis, cell cycle arrest, suppressing glycolysis and cholesterol synthesis after activation of AMPK in gefitinib-resistant H1975 cells.

Azalanstat HCl is an anti-obesity drug acting as a lanosterol 14α-demethylase inhibitor. Azalanstat HCl has been shown to inhibit cholesterol synthesis in HepG2 cells, human fibroblasts, hamster hepatocytes and hamster liver, by inhibiting the cytochrome P450 enzyme lanosterol 14 alpha-demethylase. When administered orally to hamsters fed regular chow, RS-21607 (50 mg/kg/day) lowered serum cholesterol in a dose-dependent manner (ED50 = 62 mg/kg) in a period of 1 week. It preferentially lowered low density lipoprotein (LDL) cholesterol and apo B relative to high density lipoprotein (HDL) cholesterol and apo A-1.