Pharmacological profile of F 12511, (S)-2',3', 5'-trimethyl-4'-hydroxy-alpha-dodecylthioacetanilide a powerful and systemic acylcoenzyme A: cholesterol acyltransferase inhibitor.

  title={Pharmacological profile of F 12511, (S)-2',3', 5'-trimethyl-4'-hydroxy-alpha-dodecylthioacetanilide a powerful and systemic acylcoenzyme A: cholesterol acyltransferase inhibitor.},
  author={Didier Junqu{\'e}ro and Philippe Oms and Elisabeth Carilla-Durand and Jean Marie Autin and J. P. Tarayre and Annelies Degryse and Jean François Patoiseau and F. C. Colpaert and Andr{\'e} Delhon},
  journal={Biochemical pharmacology},
  volume={61 1},

Direct Effect of F12511, A Systemic Inhibitor of Acyl-CoA Cholesterol Acyltransferase on Bovine Aortic Endothelial Cells

F12511 failed to modify the expression of the proinflammatory associated proteins PECAM and CD40L in the endothelium but protected eNOS expression in the vascular cells exposed to inflammatory conditions.

Effect of SMP-500, a Novel Acyl-CoA:Cholesterol Acyltransferase Inhibitor, on the Cholesterol Esterification and Its Hypocholesterolemic Properties

Results indicate that SMP-500 is a potent and competitive ACAT inhibitor and may have a therapeutic potential for treating hypercholesterolemia and atherosclerosis.

Pharmacological Profile of SMP-797, a Novel Acyl-Coenzyme A: Cholesterol Acyltransferase Inhibitor with Inducible Effect on the Expression of Low-Density Lipoprotein Receptor

It is suggested that SMP-797 is a novel hypocholesterolemic agent showing a cholesterol-lowering effect in which the increase of hepatic low-density lipoprotein receptor expression as well as the inhibition of acyl-coenzyme A: cholesterol acyltransferase is involved.

Anti-Atherosclerotic Properties of the Acyl-coenzyme A:Cholesterol Acyltransferase Inhibitor F 12511 in Casein-Fed New Zealand Rabbits

The data suggest that the combination of endogenous hypercholesterolemia with endothelial injury in the rabbit may offer a useful model to study atherosclerosis; lipid lowering by F 12511 reduces the incidence of vascular lesions and macrophage infiltration and may reinforce the fibrous skeleton of the atheroma.

Roles of acyl-coenzyme A : cholesterol acyltransferase-1 and -2

There is compelling evidence implicating a role for ACat1 in macrophage foam-cell formation, and for ACAT2 in intestinal cholesterol absorption, however, further studies at the biochemical and cell biological levels are needed in order to clarify the functional roles of ACAT1 and ACat2 in the VLDL or chylomicron synthesis/assembly process.

Effect of SMP-500, a Novel Acyl-CoA:Cholesterol Acyltransferase Inhibitor, on Serum Cholesterol Level and LDL Cholesterol Clearance in Hamsters with Induced Hyperlipidemia

The results suggest that the cholesterol-lowering effect of SMP-500 is due, not only to the inhibition of ACAT, but also to the increase in cholesterol clearance from the blood.

Isoform-specific inhibitors of ACATs: recent advances and promising developments.

The selectivity study indicated that fungal pyripyropene A (PPPA) is only an ACAT2-specific inhibitor, and PPPA proved orally active in atherogenic mouse models, indicating it possessed cholesterol-lowering and atheroprotective activities.

Human acyl-CoA:cholesterol acyltransferase (ACAT) and its potential as a target for pharmaceutical intervention against atherosclerosis.

The merit of ACAT as a drug target for pharmaceutical interventions against atherosclerosis is discussed, and the current knowledge on the biochemical properties of human ACATs is outlined.



Subacute toxicity of a novel inhibitor of acyl-CoA: cholesterol acyltransferase in beagle dogs.

PD 132301-2 or one of its metabolites has potent adrenocorticolytic properties and limited hepatotoxic properties by mechanism(s) that are likely independent of systemic ACAT inhibition.

Inhibition of acyl-CoA: cholesterol acyltransferase decreases apolipoprotein B-100-containing lipoprotein secretion from HepG2 cells.

Investigation of the effect of the specific stimulation and inhibition of the rate-limiting enzyme of the cholesterol esterification, acyl-CoA:cholesterol acyltransferase (ACAT), on the lipid and on the apoB-100 secretion rate from a human hepatoma cell line showed the idea of a close relationship between ACAT activation, leading to increased cholesteryl ester availability, and apo B-100-containing lipoproteins secretion.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and hepatic apolipoprotein B secretion.

Important advances in our understanding of the regulation of hepatic apolipoprotein B secretion have been made in the past year. A diverse group of studies have provided evidence that the inhibition

Immunodepletion experiments suggest that acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) protein plays a major catalytic role in adult human liver, adrenal gland, macrophages, and kidney, but not in intestines.

The results showed that ACAT activity was immunodepleted 90% in liver, 98% in adrenal gland, 91% in macrophages, 80% in kidney, and 19% in intestines, suggesting that ACat-1 protein plays a major catalytic role in all of the human tissue/cell homogenates examined except intestines.

Effect of the acyl‐CoA: cholesterol acyltransferase inhibitor DuP 128 on cholesterol absorption and serum cholesterol in humans

ACAT inhibitors limit cholesterol absorption in humans; however, the magnitude of the effect, as exemplified by DuP 128, is small.

Regulation and Immunolocalization of Acyl-Coenzyme A:Cholesterol Acyltransferase in Mammalian Cells as Studied with Specific Antibodies (*)

Production of specific polyclonal antibodies against ACAT is reported by immunizing rabbits with the recombinant fusion protein composed of glutathione S-transferase and the first 131 amino acids of ACAT protein, suggesting that cholesterol concentration in the endoplasmic reticulum may be the major determinant for regulating ACAT activity in the intact cells.

Acyl-coenzyme A:cholesteryl acyltransferase 2.

It is hypothesized that oversecretion of cholesteryl esters produced by the action of hepatic ACAT2 could account for the increased atherogenicity associated with cholesterol ester-enriched LDL in nonhuman primates.