Olumacostat glasaretil

SKU: orb1226652

Description

A small molecule inhibitor of acetyl coenzyme A (CoA) carboxylase (ACC); inhibits de novo lipid synthesis in primary and transformed human sebocytes; reduces saturated and monounsaturated fatty acyl chains across lipid species, including di- and triacylglycerols, phospholipids, cholesteryl esters, and wax esters; significantly reduces hamster ear sebaceous gland size; a pro-drug of TOFA with enhance delivery in vivo.Other Indication Phase 3 Clinical(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.\n(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.

Key Properties

• CAS Number: 1261491-89-7
• MW: 481.6221
• Purity: >98% (HPLC)
• Formula: C₂₆H₄₃NO₇
• SMILES: O=C(C1=CC=C(OCCCCCCCCCCCCCC)O1)OCC(N(CC(OCC)=O)C)=O
• Target: Others
• Solubility: 10 mM in DMSO

Bioactivity

• 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.
• 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Olumacostat glasaretil | DRM01B | DRM-01B

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