Avasimibe

• CAT Number: I002175
• CAS Number: 166518-60-1
• Molecular Formula: C₂₉H₄₃NO₄S
• Molecular Weight: 501.72
• Purity: ≥95%
• Synonyms: Avasimibe; [2,6-di(propan-2-yl)phenyl] N-[2-[2,4,6-tri(propan-2-yl)phenyl]acetyl]sulfamate
• Target: Acyltransferase
• Solubility: Soluble in DMSO
• Storage: Store at -20C
• IC50: 24 and 9.2 μM for ACAT1 and ACAT2
• InChI: InChI=1S/C29H43NO4S/c1-17(2)22-14-25(20(7)8)27(26(15-22)21(9)10)16-28(31)30-35(32,33)34-29-23(18(3)4)12-11-13-24(29)19(5)6/h11-15,17-21H,16H2,1-10H3,(H,30,31)
• InChIKey: PTQXTEKSNBVPQJ-UHFFFAOYSA-N
• SMILES: CC(C)C1=C(C(=CC=C1)C(C)C)OS(=O)(=O)NC(=O)CC2=C(C=C(C=C2C(C)C)C(C)C)C(C)C

Avasimibe (CAT: I002175) is a selective inhibitor of acyl-coenzyme A: cholesterol acyltransferase (ACAT) enzyme. It acts by blocking the conversion of cholesterol into cholesterol esters, thereby reducing the accumulation of cholesterol in cells. Avasimibe has been investigated for its potential use in treating dyslipidemia and atherosclerosis. It has shown the ability to lower levels of low-density lipoprotein (LDL) cholesterol and triglycerides in preclinical and clinical studies. Additionally, avasimibe has been explored for its anti-inflammatory and anti-proliferative effects. Further research is needed to determine its full therapeutic potential.

Overview of Clinical Research

Originator: Pfizer
Class: Antihyperlipidaemics
Mechanism of Action: Sterol O-acyltransferase inhibitors
Orphan Drug Status: No

Reference

1. Cardiovasc Drug Rev. 2003 Spring;21(1):33-50.

Pharmacology of the ACAT inhibitor avasimibe (CI-1011).

Llaverías G(1), Laguna JC, Alegret M.

Author information:
(1)Unitat de Farmacologia, Departament de Farmacologia i Química Facultat de
Farmàcia, Universitat de Barcelona, Barcelona, Spain.

Avasimibe is a novel orally bioavailable ACAT inhibitor, currently under clinical
development (phase III trials). It was safe when administered to rats, dogs, and
humans. In vitro studies in human macrophages demonstrated that avasimibe reduces
foam cell formation not only by enhancing free cholesterol efflux, but also by
inhibiting the uptake of modified LDL. The concentration-dependent reduction in
cellular cholesteryl ester content in these cells was not accompanied by an
increase in intracellular free cholesterol, which is in agreement with a good
safety profile for avasimibe. In the liver, avasimibe caused a significant
reduction in the secretion of apo B and apo B-containing lipoproteins into
plasma. Avasimibe induced cholesterol 7alpha-hydroxylase and increased bile acid
synthesis in cultured rat hepatocytes, and its administration to rats did not
produce an increase in lithogenicity index of the bile. The hypolipidemic
efficacy of the compound was demonstrated in cholesterol-fed as well as in
non-cholesterol-fed animals. In these models, plasma cholesterol levels were
reduced, mainly due to the decrease in the non-HDL cholesterol fraction. Clinical
data are scarce, but in a study performed in 130 men and women with combined
hyperlipidemia and hypoalphalipoproteinemia, avasimibe, 50-500 mg/day,
significantly reduced plasma total triglyceride and VLDL-cholesterol. Although
total cholesterol, LDL-cholesterol, and HDL-cholesterol were unchanged, it must
be stressed that animal data suggest that avasimibe may have direct
antiatherosclerotic activity in addition to its cholesterol-lowering effect.
Avasimibe treatment can also contribute to increase plaque stability, as it
reduces the accumulation of lipids in the arterial wall, inhibits macrophage
infiltration into the media and reduces matrix metalloproteinase expression and
activity. Moreover, avasimibe and statins have been shown to have synergistic
effects, and the combination therapy may not only inhibit atherosclerotic lesion
progression but also induce lesion regression, independently of changes in plasma
cholesterol.