High impact information on NB 598

• In contrast, intravitreal injection of NB-598, a specific inhibitor of squalene epoxidase, eliminated the conversion of newly synthesized squalene to sterols without obvious pathology [1].
• Surprisingly, enantiomeric cholesterol also supported cell growth, even in the presence of NB-598 [2].
• In contrast, NB-598 had no effect on the message levels of these genes when fed to HeLa cells grown in FBS [3].
• Accelerated degradation of HMG-CoA reductase was observed when NB-598-treated cells were incubated with both MVA and sterols [4].
• These results demonstrate that the induction of LDL receptor activity by NB-598 is due to increases in mRNA and protein through the inhibition of cholesterol synthesis at the squalene epoxidase step [5].

Biological context of NB 598

• Effect of an inhibitor of squalene epoxidase, NB-598, on lipid metabolism in Hep G2 cells [6].

Anatomical context of NB 598

• We have reported previously that NB-598 competitively inhibits human squalene epoxidase and strongly inhibits cholesterol synthesis from [14C]acetate in cultured cells [5].
• After incubating Caco-2 cells with 10 microM NB-598, a slight reduction in cellular ACAT activity was also observed [7].

Associations of NB 598 with other chemical compounds

• The expression of rat SE in the isolated terbinafine-resistant clone was confirmed by its survival in the presence of either terbinafine or an inhibitor specific for mammalian SE, NB-598, but not in the presence of both terbinafine and NB-598 [8].
• In the presence of LDL or cycloheximide, NB-598 did not increase LDL receptor activity [5].
• The accelerated degradation of HMG-CoA reductase in met-18b-2 cells, which is induced by the addition of MVA, was inhibited by the presence of the squalene synthase inhibitor, zaragozic acid/squalestatin, or the squalene epoxidase inhibitor, NB-598 [4].
• A squalene epoxidase inhibitor, NB-598, affected neither triglyceride biosynthesis nor its inhibition by ER-27856 and RPR-107393 [9].
• The requirement of the co-factors, the S105 fraction or Triton X-100, and NADPH-cytochrome c reductase, the pH dependency for enzyme activity, and the sensitivity to NB-598 seen with both enzymes suggest that rSE has properties very similar to rat microsomal SE [10].

Gene context of NB 598

• Terbinafine, an inhibitor of fungal squalene epoxidase, inhibited the enzyme in a non-competitive manner, while NB-598, an inhibitor of mammalian squalene epoxidase, barely inhibited it in a partially non-competitive manner [11].
• LDL receptor mRNA was also induced by NB-598 [5].
• Incubation of Hep G2 cells with NB-598 for 18 h increased HMG-CoA reductase activity in a dose-dependent manner [5].
• NB-598: a potent competitive inhibitor of squalene epoxidase [12].
• When microsomes prepared from control Caco-2 cells were incubated with 10 microM NB-598, acyl CoA:cholesterol acyltransferase (ACAT) activity was inhibited slightly [7].

Analytical, diagnostic and therapeutic context of NB 598

• Furthermore, multiple oral administration of NB-598 decreased serum cholesterol levels in dogs (Horie, M., Tsuchiya, Y., Hayashi, M., Iida, Y., Iwasawa, Y., Nagata, Y., Sawasaki, Y., Fukuzumi, H., Kitani, K., and Kamei, T. (1990) J. Biol. Chem. 265, 18075-18078) [5].

References