[CAS NO. 1261491-89-7] Olumacostatglasaretil
PRODUCTS SPECIFICATIONS [1261491-89-7]
DESCRIPTION [1261491-89-7]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 481.62 |
| Molecular Formula | C26H43NO7 |
| SMILES | O=C(C1=CC=C(OCCCCCCCCCCCCCC)O1)OCC(N(CC(OCC)=O)C)=O |
Summary
Olumacostat glasaretil is a small molecule inhibitor of acetyl coenzyme A carboxylase ( ACC ).
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. 14 C-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 [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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 [1] . 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 [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT02431052 | Dermira, Inc.|Eli Lilly and Company |
Acne Vulgaris
|
April 2015 | Phase 2 |
| NCT01936324 | Dermira, Inc.|Eli Lilly and Company |
Acne Vulgaris
|
August 2013 | Phase 1|Phase 2 |
| NCT03028363 | Dermira, Inc.|Eli Lilly and Company |
Acne Vulgaris
|
December 27, 2016 | Phase 3 |
| NCT03073486 | Dermira, Inc.|Eli Lilly and Company |
Acne Vulgaris
|
February 6, 2017 | Phase 3 |
| NCT03127956 | Dermira, Inc.|Eli Lilly and Company |
Acne Vulgaris
|
March 21, 2017 | Phase 3 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 125 mg/mL ( 259.54 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.0763 mL | 10.3816 mL | 20.7633 mL |
| 5 mM | 0.4153 mL | 2.0763 mL | 4.1527 mL |
| 10 mM | 0.2076 mL | 1.0382 mL | 2.0763 mL |
References
- [1] Hunt DW, et al. Inhibition of Sebum Production with the Acetyl Coenzyme A Carboxylase Inhibitor OlumacostatGlasaretil. J Invest Dermatol. 2017 Mar 1. pii: S0022-202X(17)30186-0.
- [2] Bissonnette R, et al. Olumacostat glasaretil, a novel topical sebum inhibitor, in the treatment of acne vulgaris: A phase IIa, multicenter, randomized, vehicle-controlled study. J Am Acad Dermatol. 2017 Jan;76(1):33-39.
Synonyms