Disease relevance of Lss

• Induction of cataracts in experimental animals is a common toxic feature of oxidosqualene cyclase (OSC) inhibitors [1].
• Interestingly, DATS, an OSC which lacks activity against BP-induced lung cancer in mice, was a relatively more potent inducer of pi class GST isoenzyme than DAS, which is a potent inhibitor of BP-induced lung tumorigenesis [2].

High impact information on Lss

• Lipid metabolic enzymes identified in both preparations include hormone-sensitive lipase, lanosterol synthase, NAD(P)-dependent steroid dehydrogenase-like protein, acyl-CoA synthetase, long chain family member (ACSL) 1, and CGI-58 [3].
• In view of this finding and the fact that U18666A and other OSC inhibitors are highly lipophilic cationic tertiary amines, we tested the hypothesis that the cataractogenic effect of U18666A is related to direct perturbation of lens membrane structure and function [1].
• BIBB 515 (1-(4-chlorobenzoyl)-4-((4-(2-oxazolin-2-yl) benzylidene))piperidine) is a potent and selective inhibitor of 2,3-oxidosqualene cyclase (OSC) [EC 5.4.99.7] [4].
• Expression of these biochemical markers of osteoblasts occurred to a lesser extent in a second line (OSC) and was undetectable in the third line (OSB) [5].
• Among these compounds, squalene maleimide was the most active toward mammalian OSC, whereas squalene Ellman behaved as an irreversible inhibitor of OSC from yeast [6].

Biological context of Lss

• Kinetic studies on the cyclization of 2,3(S)-oxido and 2,3(S):22(S),23-dioxido[14C]squalene catalyzed by liver oxidosqualene-lanosterol cyclase revealed a specificity (in terms of V/Km) of the enzyme for the diepoxide [7].
• In order to obtain new, site-directed irreversible inhibitors of OSC, a series of squalene derivatives containing functional groups that can link covalently to an active-site thiol group was designed [6].

Associations of Lss with chemical compounds

• 2,3-Oxidosqualene cyclases (OSC) are enzymes which convert 2,3-oxidosqualene (OS) into polycyclic triterpenoids such as lanosterol, cycloartenol, and alpha- and beta-amyrin [6].

References