Avasimibe

SKU: orb1305068

Description

Avasimibe (PD-148515) is an orally active ACAT inhibitor (IC50: 3.3 μM) that reduces arterial cholesterol deposition. It also inhibits CYP2C9, 1A2, and 2C19 isoenzymes. This compound is used in research on atherosclerosis and drug metabolism, with applications in both in vitro enzymatic assays and in vivo models of hyperlipidemia.

Research Area

Metabolism Research

Key Properties

• CAS Number: 166518-60-1
• MW: 501.72
• Purity: 99.16%
• Formula: C₂₉H₄₃NO₄S
• SMILES: CC(C)c1cc(C(C)C)c(CC(=O)NS(=O)(=O)Oc2c(cccc2C(C)C)C(C)C)c(c1)C(C)C
• Target: Cytochromes P450,Acyltransferase
• Solubility: Ethanol:2 mg/mL (3.99 mM);10% DMSO+90% Corn Oil:5 mg/mL (9.97 mM);DMSO:102 mg/mL (203.3 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  CYP2C9:2.9 μM|ACAT1:24 μM|ACAT:3.3 μM|CYP1A2:13.9 μM|CYP2C19:26.5 μM|ACAT2:9.2 μM
• In Vivo:
  In HepG2 cells incubated for 24 h, Avasimibe (0.01/1/10 μM) reduced ApoB secreted into the culture medium by 25%, 27% and 43%, respectively. In human monocyte-derived macrophages, Avasimibe (1 μg/ml) lowered esterified and total cholesterol by inhibiting LDL binding and reducing scavenger receptor counts during the foam cell formation phase.Pre-warming of Avasimibe (2 μg/ml) with LDL (10 μg/ml) resulted in enhanced cholesterol efflux from HMM foam cells. Avasimibe decreases ApoB secretion by enhancing intracellular ApoB degradation, but does not affect its ApoB synthesis. In IC-21 macrophages, Avasimibe inhibited ACTC (IC50: 3.3 μM). In glioma cells, Avasimibe inhibited cholesteryl ester synthesis and ACAT-1 expression. Avasimibe inhibited glioma cell growth by inducing apoptosis caused by cell cycle arrest and caspase-8/3 activation.Avasimibe dose-dependently inhibited lipoprotein(a) accumulation in primary monkey liver cell cultures (11.9% -31.3%), which was associated with a decrease in ApoA.
• In Vitro:
  In HepG2 cells incubated for 24 h, Avasimibe (0.01/1/10 μM) reduced ApoB secreted into the culture medium by 25%, 27% and 43%, respectively. In human monocyte-derived macrophages, Avasimibe (1 μg/ml) lowered esterified and total cholesterol by inhibiting LDL binding and reducing scavenger receptor counts during the foam cell formation phase.Pre-warming of Avasimibe (2 μg/ml) with LDL (10 μg/ml) resulted in enhanced cholesterol efflux from HMM foam cells. Avasimibe decreases ApoB secretion by enhancing intracellular ApoB degradation, but does not affect its ApoB synthesis. In IC-21 macrophages, Avasimibe inhibited ACTC (IC50: 3.3 μM). In glioma cells, Avasimibe inhibited cholesteryl ester synthesis and ACAT-1 expression. Avasimibe inhibited glioma cell growth by inducing apoptosis caused by cell cycle arrest and caspase-8/3 activation.Avasimibe dose-dependently inhibited lipoprotein(a) accumulation in primary monkey liver cell cultures (11.9% -31.3%), which was associated with a decrease in ApoA.
• Cell Research:
  For foam cell formation, the growth medium (RPMI medium containing 10% human serum) is aspirated and the BMMs are rinsed four times with RPMI medium, and then HMMs are exposed to RPMI medium containing bovine serum albumin (BSA, 0.2%) and dimethylsulfoxide (DMSO, 0.2%, vehicle for CI-1011) (control medium) with and without agacLDL (100 μg protein/ml) and CI-1011 (1 μg/ml) for 48 hours. For cholesterol efflux experiments, HMMs are preincubated with ag-acLDL (100 μg protein/ml) for 24h, and then exposed to control RPMI medium with and without HDL (100 μg protein/ml), CI-1011 (2 μg/ml) or HDL plus CI-1011 (2 μg/ml) for 24–48 hours. Additionally, the appearance of [14C]FC in the medium is monitored by first preincubating HMMs with RPMI medium containing ag-acLDL (100 μg protein/ml) radiolabeled with [4-14C]FC (0.5 μCi/ml) in an ethanolic spritz (final concentration, 0.1%) for 24 h. The medium is removed, cells rinsed three times with RPMI medium, and then cells are exposed to control RPMI medium with and without CI-1011 (1–10 μg/ml) for 4–48 h. At each time point, the medium is aspirated and centrifuged to pellet nonadherent cells. The appearance of [14C]FC in the medium is measured by liquid scintillation spectroscopy. Cellular lipids are extracted using hexane:isopropanol (3:2, v/v) for 1 h. The distribution of cellular radiolabeled cholesterol is measured by subjecting an aliquot of the cell extract and FC and EC standards to thin layer chromatography using petroleum ether:hexane:glacial acetic acid solvent system (85:15:2, v/v). The percent FC efflux is calculated as: medium [14C]FC dpm/ cell [14C] dpm×100. FC and TC mass are quantified by gas liquid chromatography using stigmasterol (1 mg/ml) as an internal standard. EC mass is calculated as the difference between TC and FC, and all values are normalized to cell protein. The MBC is de ned as the lowest concentration that exhibited 99.9% or more reduction of the numbers of colonies compared with the cfu in the initial inoculum. (Only for Reference)

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

SOAT, mono- acylglycerol acyltransferase, Inhibitor, inhibit, PD148515, PD-148515, PD 148515, orally, Avasimibe, active, Acyltransferase, acyl-CoA:cholesterol acyltransferase, ACAT1, ACAT, ACAT2, CYP1A2, CYP2C19, CYP2C9, Diglyceride acyltransferase, Diacylglycerol acyltransferase, CI 1011, CI-1011, CI1011

Compound Identifiers

PubChem CID

166558