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

@article{Junquro2001PharmacologicalPO,
  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},
  year={2001},
  volume={61 1},
  pages={
          97-108
        }
}
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22 Citations

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.

F 12511, a novel ACAT inhibitor, and atorvastatin regulate endogenous hypercholesterolemia in a synergistic manner in New Zealand rabbits fed a casein-enriched diet.

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.

ACAT inhibitors: the search for a novel and effective treatment of hypercholesterolemia and atherosclerosis.

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.

References

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TMP-153, a novel ACAT inhibitor, lowers plasma cholesterol through its hepatic action in golden hamsters.

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.

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