166518-60-1 Usage
Description
Avasimibe is a selective inhibitor of Cholesterol Acyltransferase 1 (ACAT1) and CYP2C9, a class of enzymes involved in cholesterol metabolism and drug metabolism, respectively. It has been recognized for its potential in inducing apoptosis in glioma cell lines, serving as a model for glioblastoma treatment.
Uses
Used in Pharmaceutical Industry:
Avasimibe is used as an inhibitor of acyl-coenzyme A: cholesterol acyltransferase (ACAT) for testing its combination with direct-acting antivirals (DAAs) and to evaluate its effect on lipid droplet accumulation in acidosis-adapted cancer cells. This application aims to explore its potential synergistic effects and its role in managing lipid metabolism in cancer treatment.
Used in Research and Development:
Avasimibe is utilized as an inhibitor of ACAT to assess cholesterol esterification in Trypanosoma cruzi, the causative agent of Chagas disease. This application is crucial for understanding the enzyme's role in the disease's progression and for developing targeted therapies.
Additionally, Avasimibe's ability to induce apoptosis in glioma cell lines positions it as a potential candidate for glioblastoma treatment, further emphasizing its importance in the field of oncology and drug development.
Biological Activity
avasimibe is an orally bioavailable inhibitor of the acyl coenzyme a: cholesterol acyltransferase (acat) with ic50 value of 60nm [1].avasimibe is developed from a strategy to design acat inhibitors with improved bioavailability. it also has solution stability at acidic ph. in the in vitro assay, the ic50 value is dependent on the concentration of microsomes, the amount of membrane available for adsorption as well as the presence of bsa. the treatment of avasimibe during the process of lipid loading causes a concentration-dependent reduction in cellular cholesteryl ester content. this reduction is not accompanied by the accumulation of intracellular free cholesterol, indicating a better safety profile for avasimibe than other acat inhibitors. avasimibe can also reduce the synthesis and secretion of apo b 100 (a component of vldl) in hepg2 cells. in addition, avasimibe can increase the total bile acid synthesis in rat hepatocytes at the concentration of 3μm [1].apart from the antiatherosclerotic efficacy, avasimibe is also found to take participate in the modulation of app trafficking. it can delay and reduce the maturation of app, limiting the availability of app holoprotein for aβ-generatiion [2].
Biochem/physiol Actions
Avasimibe (CI-1011) is an orally bioavailable Acyl-CoA:Cholesterol O-Acyltransferase (ACAT) inhibitor. It was originally developed as an antilepic drug, and was shown to significantly reduce plasma total triglyceride and VLDL-cholesterol, but later clinical trials were disappointing. ACAT has also been investigated as a potential therapeutic target for Alzheimer′s disease. Recent studies have looked at the effects of avasimibe in reducing amyloid pathology by limiting generation and increasing clearance of diffusible amyloid-beta (Abeta).
references
[1] llaverías g, laguna jc, alegret m. pharmacology of the acat inhibitor avasimibe (ci-1011). 2003 spring;21(1):33-50.[2] huttunen hj, peach c, bhattacharyya r, barren c, pettingell w, hutter-paier b, windisch m, berezovska o, kovacs dm. inhibition of acyl-coenzyme a: cholesterol acyl transferase modulates amyloid precursor protein trafficking in the early secretory pathway. faseb j. 2009 nov;23(11):3819-28.
Check Digit Verification of cas no
The CAS Registry Mumber 166518-60-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,6,6,5,1 and 8 respectively; the second part has 2 digits, 6 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 166518-60:
(8*1)+(7*6)+(6*6)+(5*5)+(4*1)+(3*8)+(2*6)+(1*0)=151
151 % 10 = 1
So 166518-60-1 is a valid CAS Registry Number.
InChI:InChI=1/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)
