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Chemical Compound Review:

CHEBI:11814 4-[2-[3-[[(2R)-4- [[[(2R,3S,4R,5R)-5-(6...

Synonyms: KST-1A1759, AR-1A7374, AC1L3M7S, AC1Q5VD4, 1553-55-5, ...

Vaziri, N.D. et al., Beirne, O.R. et al., Sumi, S. et al., Walli, A.K. et al., Agarwal, B. et al., et al.

Meier, Schlienger, Kraenzlin, Schlegel, Jick, Han, Ryu, Hong, Ko, Pak, Kim, Park, Kim, Kusama, Mukai, Iwasaki, Tatsuta, Matsumoto, Akedo, Inoue, Nakamura, Wang, Solomon, Mogun, Avorn, Wheeler, Smutney, Check, Rusyn, Schulte-Hermann, Thurman,

Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of EINECS 216-301-7

BACKGROUND & AIMS: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, target liver HMG-CoA and are of proven benefit in the prevention of coronary heart disease [1].
3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors reduce human pancreatic cancer cell invasion and metastasis [2].
Discussion on 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors reduce human pancreatic cancer cell invasion and metastasis [3].
BACKGROUND & AIMS: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (HRIs) were found incidentally to reduce new cases of colon cancer in 2 large clinical trials evaluating coronary events, although most patients in both treatment and control group were taking nonsteroidal anti-inflammatory drugs (NSAIDs) [4].
OBJECTIVE: To determine the effects of fluvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, combined with moderate alcohol consumption on lipid profiles and hepatic function in patients with primary hypercholesterolemia [5].

Psychiatry related information on EINECS 216-301-7

Epidemiological studies demonstrate a relationship between statin [3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor] usage and reduced risk of developing Alzheimer's disease [6].

High impact information on EINECS 216-301-7

Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been shown to be effective and safe in lowering cholesterol levels after cardiac transplantation [7].
We studied the effects of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on serum levels of lipoproteins and ubiquinone-10-in seven heterozygous patients with familial hypercholesterolemia [8].
Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, which are approved for cholesterol reduction, may also be beneficial in the treatment of inflammatory diseases [9].
CONTEXT: Recent animal studies have found that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lipid-lowering drugs (statins) substantially increase bone formation, but whether statin use in humans results in clinically meaningful bone formation or a reduction in the risk of osteoporotic fractures is not known [10].
CONTEXT: Recent animal studies have suggested that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) increase bone formation, volume, and density [11].

Chemical compound and disease context of EINECS 216-301-7

In the present study, the effect of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A, the rate-limiting enzyme of cholesterol synthesis, on the growth of five pancreatic cancer cell lines (human-CAV, MIA Paca2, CAPAN2 and PANC1, and hamster-H2T) in vitro and of two cell lines (CAV and H2T) in vivo was examined [12].
Unlike the normal liver, numerous transplantable rodent and human hepatomas are unable to alter their rate of sterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-GoA) reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34] activity in response to a dietary cholesterol challenge [13].
The mechanism of action of serum lipoproteins and 25-hydroxycholesterol on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity in hepatoma tissue culture (HTC) cells was investigated using antiserum against purified rat liver HMG-CoA reductase (Heller, R. A., and Shrewsbury, M. A. (1976)J. Biol. Chem. 251, 3815-3822) [14].
Biol. Chem. 260, 9393-9398] 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (EC 1.1.1.88), overexpressed in Escherichia coli (1), has been purified to electrophoretic homogeneity in 75% yield (final specific activity 48 mumols of NAD+ reduced per min/mg protein) [15].
In the present study, the effects of NB-598 on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and low-density-lipoprotein (LDL) receptor were examined using a human hepatoma cell line Hep G2 [16].

Biological context of EINECS 216-301-7

Statins, known as inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, exhibit numerous functions related to inflammation, such as MHC class II down-regulation, interference with T cell adhesion, and induction of apoptosis [17].
However, in comparison with fibroblasts, the LDL receptor and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity in J774 cells are relatively resistant to down-regulation by LDL or 25-hydroxycholesterol, leading to receptor-mediated CE storage [18].
Measurements oof hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34) activity showed decreases in specific activity and total liver activity in portacaval shunt rats, but the enzyme diurnal rhythm remained [19].
Mevalonic acid is limiting for N-linked glycosylation and translocation of the insulin-like growth factor-1 receptor to the cell surface. Evidence for a new link between 3-hydroxy-3-methylglutaryl-coenzyme a reductase and cell growth [20].
The attenuation of catalytic activity that accompanies phosphorylation of Ser871 of Syrian hamster 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (EC 1.1.1.34) reflects primarily the introduction of negative charge (Omkumar, R. V., Darnay, B. G., and Rodwell, V. W. (1994) J. Biol. Chem. 269, 6810-6814) [21].

Anatomical context of EINECS 216-301-7

Lymphocytes took up 20-fold more LP-X than PC and the activity of 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase was depressed by LP-X [22].
Because leaflet calcification occurs in areas of lipoprotein deposition, we hypothesised that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG COA) reductase inhibitors (statins) might slow aortic valve calcium (AVC) accumulation [23].
Overproduction of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in yeast resulted in striking morphological effects on the structure of intracellular membranes [24].
Genetic complementation analysis of 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency in cultured fibroblasts [25].
3-Hydroxy-3-methylglutaryl coenzyme a reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture [26].

Associations of EINECS 216-301-7 with other chemical compounds

We performed studies to determine the activity of dietary psyllium on hepatic 7 alpha-hydroxylase, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase and LDL receptor expression in the hamster [27].
It functions by inhibiting the enzyme, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 1.1.1.34), that is required for the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonic acid [28].
A beta-lactone isolated from Fusarium sp. has been shown to be a potent specific inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase [(S)-3-hydroxy-3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA-acetylating), EC, 4.1.3.5] from rat liver [29].
Cholesterol biosynthesis and uptake are controlled by a classic end product-feedback mechanism whereby elevated cellular sterol levels suppress transcription of the genes encoding 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase, HMG-CoA reductase, and the low-density lipoprotein receptor [30].
The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor lovastatin induces growth arrest and cell death in certain cancer cell types [31].

Gene context of EINECS 216-301-7

The two yeast genes for 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, HMG1 and HMG2, each encode a functional isozyme [32].
Hepatic 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7alpha-hydroxylase, low-density lipoprotein (LDL) receptor and acyl Co A:cholesterol acyltransferase (ACAT) were measured by Western blot and plasma lecithin:cholesterol acyltransferase (LCAT) protein was measured by enzyme-linked immunosorbent assay (ELISA) [33].
In addition, the PPARalpha-regulated genes farnesyl pyrophosphate synthase and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase were significantly increased in wild-type mice [34].
We measured acyl-coenzyme A:cholesterol acyltransferase (ACAT) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activities in liver microsomes [35].
The present study investigated whether 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition affects CCR2 gene expression and CCR2-dependent monocyte recruitment [36].

Analytical, diagnostic and therapeutic context of EINECS 216-301-7

Clinical trials of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statin therapy have demonstrated that baseline or treated low-density lipoprotein (LDL) cholesterol levels are only weakly associated with net coronary angiographic change or cardiovascular events [37].
Molecular cloning of 3-hydroxy-3-methylglutaryl coenzyme a reductase and evidence for regulation of its mRNA [38].
A primary cell culture technique was used to study the effects of lipoproteins on rat hepatocyte 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity [39].
Immunoprecipitation of native rat liver microsomal 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, phosphorylated by [gamma-32P]ATP in the presence of reductase kinase, revealed a major 97-kDa 32P band which disappeared upon competition with pure unlabeled 53-kDa HMG-CoA reductase [40].
Using a fluorescence-activated cell sorting technique designed to screen for cells defective in the regulated degradation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, we isolated a squalene synthase-deficient mutant of Chinese hamster ovary cells [41].

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