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• W2336695563 abstract "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]. In rats and mice BIBB 515 inhibited OSC in vivo in a dose-dependent manner after 1, 3, and 5 h with ED50 values from 0.2 to 0.5 mg/kg (1 to 5 h) in rats and 0.36 (1 h) to 15.5 (3 h) and 33.3 (5 h) mg/kg in mice. Inhibition of [14C]acetate incorporation into sterols was found to parallel the effects on OSC when measured after 1 h (mice) or 3 h (rats). ED50 calculated were 0.9 mg/kg (mice) and 0.1 mg/kg (rats). Dose-dependent lipid-lowering activity was seen in normolipemic hamsters after 11 days treatment (-19% for total cholesterol and -32% for VLDL + LDL cholesterol at 55 mg/kg BIBB 515 per day) and in hyperlipemic hamsters after 25 days (-25% for total cholesterol and -59% for LDL-cholesterol at 148 mg/kg BIBB 515 per day). Calculation of kinetic parameters revealed no relevant differences between control and treatment groups in LDL clearance or fractional catabolic rates, but significant reductions of LDL production rates (-30% to -54%). Liver LDL receptor mRNA of the treated animals was not or only slightly increased. Liver VLDL secretion as measured by the Triton WR1339 method was reduced after BIBB 515 in rats and hamsters. It is concluded that the lipid-lowering effect of BIBB 515 is mainly the result of an inhibition of LDL production rather than due to an increase in LDL catabolism. OSC inhibitors may offer a novel approach for lipid-lowering therapy." @default.
• W2336695563 created "2016-06-24" @default.
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• W2336695563 date "1997-03-01" @default.
• W2336695563 modified "2023-10-18" @default.
• W2336695563 title "Effects of a novel 2,3-oxidosqualene cyclase inhibitor on cholesterol biosynthesis and lipid metabolism in vivo" @default.
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• W2336695563 doi "https://doi.org/10.1016/s0022-2275(20)37264-3" @default.
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