Avasimibe (CI-1011) is a novel orally bioavailable ACAT inhibitor with IC50 values of 2.9, 13.9, 26.5 µM for CYP2C9, CYP1A2 and CYP2C19, respectively. Avasimibe inhibited ACAT-1 expression and cholesterol ester synthesis in glioma cell lines. Moreover, Avasimibe inhibited the growth of the cells by inducing cell cycle arrest and induced apoptosis as a result of caspase-8 and caspase-3 activation. 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.
| Molecular Weight | 501.72 |
| Formula | C29H43NO4S |
| CAS Number | 166518-60-1 |
| Solubility (25°C) | DMSO ≥90 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related Cytochrome P450 (e.g. CYP17) Products |
|---|
| Cytochrome P450 reductase
Cytochrome P450 reductase is a NADPH-cytochrome reductase. |
| 20-SOLA
20-SOLA is a water-soluble 20-HETE antagonist. |
| TS-011
TS-011 is a selective inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis. |
| Dibromo-dodecenyl-methylsulfimide
Dibromo-dodecenyl-methylsulfimide is a selective inhibitor of 20-HETE synthesis and attenuates the vasodilatory response to sodium nitroprusside (SNP). |
| Abiraterone decanoate
Abiraterone decanoate is a novel, long-acting Abiraterone precursor compound that also exhibits high CYP17 cleavage enzyme inhibition selectivity for prostate cancer related studies. |
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