kr-30450 and Hypercholesterolemia

kr-30450 has been researched along with Hypercholesterolemia* in 1 studies

Other Studies

1 other study(ies) available for kr-30450 and Hypercholesterolemia

Article	Year
Biochemical basis for a cholesterol-lowering activity of 2-[2"-(1",3"-dioxolane)]-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6- nitro-2H-1-benzopyran (SKP-450), a novel antihypertensive agent. Biochemical pharmacology, 1999, Mar-01, Volume: 57, Issue:5 Administration (p.o.) of SKP-450, 2-[2"-(1",3"-dioxolane)]-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro-2H- 1-benzopyran, a novel antihypertensive agent, to hypercholesterolemic Syrian hamsters led to a significant reduction in plasma lipids in a dose-dependent manner, i.e., a 10.8% to 29% reduction in low-density lipoprotein cholesterol at doses of 0.3 to 10 mg/kg of SKP-450. SKP-450 was found to specifically inhibit the hepatic microsomal lanosterol 14alpha-methyl demethylase (14alpha-DM) in a competitive manner (Ki:2.65 microM). Furthermore, a dose-dependent decrease in the 14alpha-DM activity by SKP-450 parallelled the cholesterol synthetic rate in vitro in both the rat hepatic S10 fractions (supernatants at 10,000 g; IC50:20 microM) and Chinese hamster ovary cells (IC50:23 microM). However, this phenomenon was not seen in AR45 cells, which are deficient in 14alpha-DM, suggesting that 14alpha-DM is the major target for the inhibitory action of SKP-450 in regard to cholesterol biosynthesis. Topics: Animals; Anticholesteremic Agents; Antihypertensive Agents; Benzopyrans; Binding, Competitive; CHO Cells; Cholesterol, LDL; Cricetinae; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Hypercholesterolemia; Kinetics; Mesocricetus; Microsomes, Liver; Oxidoreductases; Pyrrolidinones; Rats; Sterol 14-Demethylase	1999

Article

Year

Biochemical basis for a cholesterol-lowering activity of 2-[2"-(1",3"-dioxolane)]-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6- nitro-2H-1-benzopyran (SKP-450), a novel antihypertensive agent.

Biochemical pharmacology, 1999, Mar-01, Volume: 57, Issue:5

Administration (p.o.) of SKP-450, 2-[2"-(1",3"-dioxolane)]-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro-2H- 1-benzopyran, a novel antihypertensive agent, to hypercholesterolemic Syrian hamsters led to a significant reduction in plasma lipids in a dose-dependent manner, i.e., a 10.8% to 29% reduction in low-density lipoprotein cholesterol at doses of 0.3 to 10 mg/kg of SKP-450. SKP-450 was found to specifically inhibit the hepatic microsomal lanosterol 14alpha-methyl demethylase (14alpha-DM) in a competitive manner (Ki:2.65 microM). Furthermore, a dose-dependent decrease in the 14alpha-DM activity by SKP-450 parallelled the cholesterol synthetic rate in vitro in both the rat hepatic S10 fractions (supernatants at 10,000 g; IC50:20 microM) and Chinese hamster ovary cells (IC50:23 microM). However, this phenomenon was not seen in AR45 cells, which are deficient in 14alpha-DM, suggesting that 14alpha-DM is the major target for the inhibitory action of SKP-450 in regard to cholesterol biosynthesis.

Topics: Animals; Anticholesteremic Agents; Antihypertensive Agents; Benzopyrans; Binding, Competitive; CHO Cells; Cholesterol, LDL; Cricetinae; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Hypercholesterolemia; Kinetics; Mesocricetus; Microsomes, Liver; Oxidoreductases; Pyrrolidinones; Rats; Sterol 14-Demethylase

1999