Olumacostat glasaretil

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

乙酰辅酶 A (CoA) 羧化酶 (ACC) 的小分子抑制剂；抑制原代和转化的人类皮脂细胞中的从头脂质合成。

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. (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.

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.

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.

Olumacostat glasaretil | DRM01B | DRM-01B

Others

Other Targets

Others

Other Indications

Other Disease

1261491-89-7

481.6221

C26H43NO7

>98% (HPLC)

10 mM in DMSO

O=C(C1=CC=C(OCCCCCCCCCCCCCC)O1)OCC(N(CC(OCC)=O)C)=O

2-Furancarboxylic acid, 5-(tetradecyloxy)-, 2-[(2-ethoxy-2-oxoethyl)methylamino]-2-oxoethyl ester

(-20℃)

With Ice Pack

≥ 2 years