ChemicalBook Product Catalog Biochemical Engineering Biochemical Reagents Agonist Inhibitors (4-Bromophenyl)[3-fluoro-4-[[6-(methyl-2-propenylamino)hexyl]oxy]phenyl]-methanone

(4-Bromophenyl)[3-fluoro-4-[[6-(methyl-2-propenylamino)hexyl]oxy]phenyl]-methanone

Product Name(4-Bromophenyl)[3-fluoro-4-[[6-(methyl-2-propenylamino)hexyl]oxy]phenyl]-methanone
CAS161582-11-2
MFC23H27BrFNO2
MW448.37
EINECS
MOL File161582-11-2.mol

Chemical Properties

Boiling point	522.8±50.0 °C(Predicted)
Density	1.235±0.06 g/cm3(Predicted)
storage temp.	2-8°C
solubility	DMF: 30 mg/ml; DMSO: 30 mg/ml; Ethanol: 30 mg/ml; Ethanol:PBS (pH 7.2) (1:2): .25 mg/ml
pka	8.88±0.50(Predicted)

Usage And Synthesis

Description

Oxidosqualene cyclase (OSC) is a microsomal enzyme that catalyzes the cyclization of monooxidosqualene to lanosterol in the cholesterol synthetic pathway. Ro 48-8071 is an inhibitor of oxidosqualene cyclase (OSC) that has low-density lipoprotein (LDL) cholesterol lowering activity similar to the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor simvastatin. It inhibits OSC from human liver microsomes and HepG2 cells with IC₅₀ values of approximately 6.5 nM and 1.5 nM, respectively. Ro 48-8071 lowered LDL cholesterol ~40% in hamsters at a dose of 150 μg/kg without affecting high-density lipoprotein levels and with no sign of liver toxicity. Ro 48-8071 increases cytochrome P3A mRNA and protein levels in primary rat and murine hepatocyte cultures with a maximal effect at 30 μM.

Uses

Ro 48-8071 is an inhibitor of oxidosqualene cyclase.

Definition

ChEBI: An aromatic ketone that is 2-fluoro-4'-bromobenzophenone in which the hydrogen at position 4 (meta to the fluoro group) is replaced by a 6-[methyl(prop-2-en-1-yl)amino]hexyl}oxy group. An inhibitor of lanosterol synthase.

in vivo

Ro 48-8071 lowers LDL-C maximally appr 60% at 150 μmol/kg per day, with no further reduction up to 300 μmol/kg per day, leaving HDL-C unchanged at all doses in hamsters. Ro 48-8071 (≥00 μmol/kg per day) increases the amount of MOS in liver of hamsters. Ro 48-8071 (300 μmol/kg per day) remarkedly and significantly reduces VLDL secretion of hamsters^[1]. Ro 48-8071 (5 or 20 mg/kg) significantly reduces in vivo tumor growth in mice, without weight loss of the mice. Furthermore, Ro 48-8071 at a concentration of 20 mg/kg, completely eradicates two of the 12 tumors being monitored in the mice in the timeframe tested^[2]. Ro 48-8071 (20 mg/day/kg body weight) leads to a rapid and sustained inhibition (>50%) of cholesterol synthesis in the whole small intestine of BALB/c mice. Sterol synthesis is also reduced in the large intestine and stomach^[4].

References

[1] O H MORAND. Ro 48-8.071, a new 2,3-oxidosqualene:lanosterol cyclase inhibitor lowering plasma cholesterol in hamsters, squirrel monkeys, and minipigs: comparison to simvastatin.[J]. Journal of Lipid Research, 1997, 38 2: 373-390.
[2] SARITA D SHENOY. Induction of CYP3A by 2,3-oxidosqualene:lanosterol cyclase inhibitors is mediated by an endogenous squalene metabolite in primary cultured rat hepatocytes.[J]. Molecular Pharmacology, 2004, 65 5: 1302-1312. DOI: 10.1124/mol.65.5.1302

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