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In vitro: Acetyl coenzyme A carboxylase controls the first, rate limiting step in fatty acid biosynthesis. Olumacostat glasaretil inhibits de novo lipid synthesis in primary and transformed human sebocytes. At 3 μM, olumacostat glasaretil reduces fatty acid synthesis to at or below baseline levels. 14C-acetate incorporation levels are 85%-90% lower for SEB-1 cultures treated with olumacostat glasaretil at 20 μM compared to control samples. At 3 μM, olumacostat glasaretil reduces sebocyte triacylglycerol, cholesteryl/wax ester, diacylglycerol, cholesterol and phospholipid levels from control values on average by approximately 86%, 57%, 51%, 39% and 37%, respectively. In vivo: Olumacostat glasaretil is a pro-drug of the ACC inhibitor 5-(tetradecyloxy)-2-furoic acid (TOFA) and is designed to enhance delivery in vivo. Topical application of olumacostat glasaretil but not TOFA significantly reduces hamster ear sebaceous gland size. HPLC analyses of hamster ear extracts shows that olumacostat glasaretil treatment increases ACC levels and the ratio of acetyl-CoA to free CoA in tested animals, indicating increased fatty acid oxidation. These changes are consistent with ACC inhibition. Matrix-assisted laser desorption/ionization (MALDI) imaging reveals that OG applied onto Yorkshire pig ears accumulates in sebaceous glands relative to the surrounding dermis. At week 12, OG treatment shows greater reductions from baseline in inflammatory lesions and noninflammatory lesions, and more patients with greater than or equal to 2-grade improvement in investigator global assessment score than vehicle.
Molecular Weight | 481.62 |
Formula | C26H43NO7 |
CAS Number | 1261491-89-7 |
Form | Solid |
Solubility (25°C) | 10mM in DMSO |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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A-908292
A-908292 is a potent and selective acetyl-CoA carboxylase 2 (ACC2) inhibitor, with an IC50 of 38 nM. A-908292 can be used for the research of fatty acid metabolism. |
CMS-121
CMS-121 is an orally active acetyl-CoA carboxylase 1 (ACC1) inhibitor. CMS-121 protects HT22 cells against ischemia and oxidative damage with EC50 values of 7 nM and 200 nM, respectively. |
PF-05221304
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MK-4074
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