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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 |
| Related Acetyl-CoA Carboxylase Products |
|---|
| CP-640186
CP-640186 is an isozyme-nonselective acetyl-CoA carboxylase (ACC) inhibitor with IC50s of 53 nM and 61 nM for rat liver ACC1 and rat skeletal muscle ACC2 respectively. |
| CP-640186 HCl
CP-640186 Hcl is an isozyme-nonselective acetyl-CoA carboxylase (ACC) inhibitor with IC50s of 53 nM and 61 nM for rat liver ACC1 and rat skeletal muscle ACC2 respectively; with improved metabolic stability vs CP-610431. |
| PF-05175157
PF-05175157 is a potent Acetyl-CoA carboxylase (ACC1) inhibitor with IC50s of 23.5±1.1 nM (rat) and 27.0±2.7 nM (human). |
| Firsocostat (ND-630)
ND-630 is an ACC inhibitor of human ACC1 and ACC2 with IC50 values of 2.1 and 6.1 nM, respectively. |
| PF-05221304
PF-05221304 is an orally bioavailable, liver-targeted inhibitor of acetyl-CoA carboxylase (ACC), an enzyme that catalyzes the first step of adipogenesis ab initio (DNL). |
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