Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

Chemical Compound Review:

CHEMBL40998 3-(decyl-dimethyl-silyl)-N- [2-(4...

Synonyms: Sandoz 58035, AG-H-16417, SureCN4430655, Sandoz 58-035, S9318_SIGMA, ...

Veldhuis, J.D. et al., Minor, L.K. et al., Ross, A.C. et al., Liza, M. et al., Warner, G.J. et al., et al.

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 San 58-035

Compound 58-035 (3-[decyldimethylsilyl]-N-[2-(4-methylphenyl)-1-phenylethyl]pro panamide) has been found to inhibit the accumulation of cholesteryl esters in both rat hepatoma (Fu5AH) cells and arterial smooth muscle cells in culture [1].

High impact information on San 58-035

Mouse peritoneal macrophages were cholesterol-enriched by incubation with acetylated low density lipoprotein and free cholesterol:phospholipid dispersions prior to the addition of an ACAT inhibitor, either Sandoz 58-035 or Pfizer CP-113,818 [2].
Sandoz 58-035 decreased cholesteryl ester synthesis significantly but did not decrease apolipoprotein B secretion from this cell line [3].
Selective inhibition of acyl coenzyme A:cholesterol acyltransferase by compound 58-035 [1].
The medium was then changed to fresh serum-free medium containing an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor (Sandoz compound 58-035) [4].
A comparison of the hydrolysis of cholesteryl ester in the presence and absence of Sandoz compound 58-035, an inhibitor of acyl CoA:cholesterol acyl transferase, by cells loaded with isotropic droplets showed that about 30% of the free cholesterol liberated by hydrolysis was reesterified regardless of the mass of free cholesterol [5].

Biological context of San 58-035

We have used a novel competitive inhibitor of acyl coenzyme A:cholesterol acyltransferase (ACAT), Sandoz compound 58-035 [3-(decyldimethyl-silyl)N-[2-(4-methyl-phenyl)1-phenylethyl propanamide], to assess the importance of the cholesterol esterification reaction in ovarian steroidogenesis [6].
(1) Interrupting the cholesteryl ester cycle by inhibiting acyl-CoA: cholesterol acyltransferase (ACAT) activity with compound 58-035 (Sandoz) resulted in an enhanced LDL-mediated down-regulation of the receptor activity [7].

Anatomical context of San 58-035

Compound 58-035 markedly (greater than or equal to 96%) inhibited ACAT activity of swine ovarian microsomes in a dose-dependent (0.1-3.5 micrograms/ml) fashion [6].
Differences in the catalytic activity of acyl-CoA:cholesterol acyltransferase and cholesterol ester hydrolases caused by treatment of hepatocytes with compound 58-035 or 25-hydroxycholesterol, or of subcellular fractions with NaF, were maintained when enzymes were assayed with cyclodextrin [8].
Activity of the enzyme acyl-CoA:cholesterol acyltransferase (ACAT) in isolated rat enterocytes was reduced by approx. 75% following a single oral dose of Sandoz compound 58-035 (30 mg.kg-1) [9].

Gene context of San 58-035

This compositional change of fatty acids in cholesteryl esters occurred even in the presence of an acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor, Sandoz 58-035 [10].

References

Selective inhibition of acyl coenzyme A:cholesterol acyltransferase by compound 58-035. Ross, A.C., Go, K.J., Heider, J.G., Rothblat, G.H. J. Biol. Chem. (1984) [Pubmed]
Cell toxicity induced by inhibition of acyl coenzyme A:cholesterol acyltransferase and accumulation of unesterified cholesterol. Warner, G.J., Stoudt, G., Bamberger, M., Johnson, W.J., Rothblat, G.H. J. Biol. Chem. (1995) [Pubmed]
Evidence for a lack of regulation of the assembly and secretion of apolipoprotein B-containing lipoprotein from HepG2 cells by cholesteryl ester. Wu, X., Sakata, N., Lui, E., Ginsberg, H.N. J. Biol. Chem. (1994) [Pubmed]
Role of the neutral lipid accessible pool in the regulation of secretion of apoB-100 lipoprotein particles by HepG2 cells. Avramoglu, R.K., Cianflone, K., Sniderman, A.D. J. Lipid Res. (1995) [Pubmed]
Triglyceride and cholesteryl ester hydrolysis in a cell culture model of smooth muscle foam cells. Minor, L.K., Rothblat, G.H., Glick, J.M. J. Lipid Res. (1989) [Pubmed]
The role of cholesterol esterification in ovarian steroidogenesis: studies in cultured swine granulosa cells using a novel inhibitor of acyl coenzyme A: cholesterol acyltransferase. Veldhuis, J.D., Strauss, J.F., Silavin, S.L., Kolp, L.A. Endocrinology (1985) [Pubmed]
Cellular free cholesterol in Hep G2 cells is only partially available for down-regulation of low-density-lipoprotein receptor activity. Havekes, L.M., de Wit, E.C., Princen, H.M. Biochem. J. (1987) [Pubmed]
Application of 2-hydroxypropyl-beta-cyclodextrin in the assay of acyl-CoA:cholesterol acyltransferase and neutral and acid cholesterol ester hydrolases. Liza, M., Romero, J.R., Chico, Y., Fresnedo, O., Ochoa, B. Lipids (1996) [Pubmed]
Esterification and absorption of cholesterol: in vitro and in vivo observations in the rat. Williams, R.J., McCarthy, A.D., Sutherland, C.D. Biochim. Biophys. Acta (1989) [Pubmed]
Accumulation of oleate-rich cholesteryl esters by acetyl-LDL in macrophages in the presence of an acyl-CoA: cholesterol acyltransferase inhibitor (Sandoz 58-035). Shimasaki, O., Mineo, C., Mowri, H., Ohkuma, S., Takano, T. Biochem. Int. (1990) [Pubmed]

Contributions to this collaborative article are from individual authors of WikiGenes or mined by the WikiGenes Data Mining Engine from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.