| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Olumacostat glasaretil targets acetyl coenzyme A carboxylase (ACC), the enzyme responsible for the first and rate-limiting step in de novo fatty acid synthesis. By inhibiting ACC, the compound reduces the production of malonyl-CoA, a key substrate for fatty acid synthesis, thereby decreasing lipid production in sebocytes. This mechanism makes it a promising therapeutic approach for acne vulgaris and other conditions characterized by excessive sebum production.
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| ln Vitro |
The acetyl coenzyme One rate-limiting step in the production of fatty acids is controlled by a carboxylase. The de novo lipid synthesis in both primary and modified human sebocytes is inhibited by olumacostat glasaretil. Olumbacostat glasaretil lowers fatty acid synthesis to baseline levels or less at 3 μM. For SEB-1 cells treated with olumacostat glasaretil at 20 μM, 14C-acetate incorporation levels are 85%-90% lower than those of control samples. Lumacostat glasaretil, at 3 μM, decreases control values in sebocyte triacylglycerol, cholesteryl/wax ester, diacylglycerol, cholesterol, and phospholipid by, on average, 86%, 57%, 51%, 39%, and 37%, respectively[1].
In vitro, Olumacostat glasaretil acts as a small molecule inhibitor of acetyl coenzyme A carboxylase (ACC), inhibiting de novo lipid synthesis in primary and transformed human sebocytes. The compound is a prodrug of the ACC inhibitor 5-(tetradecyloxy)-2-furoic acid (TOFA) and is designed to enhance delivery in vivo. Its in vitro activity is assessed by measuring the inhibition of fatty acid synthesis in cultured sebocytes and other relevant cell types. |
| ln Vivo |
Olumacostat glasaretil is a pro-drug intended to improve in vivo administration of 5-(tetradecyloxy)-2-furoic acid (TOFA), an ACC inhibitor. The size of the sebaceous glands in hamster ears is greatly reduced by topical application of olumacostat glasaretil, but not TOFA. The olumacostat glasaretil administration raises ACC levels and the ratio of acetyl-CoA to free CoA in the studied animals, indicating accelerated fatty acid oxidation, according to HPLC analysis of hamster ear extracts. These modifications align with the inhibition of ACC. In comparison to the surrounding dermis, OG administered to Yorkshire pig ears accumulates in sebaceous glands, according to matrix-assisted laser desorption/ionization (MALDI) imaging[1]. By week 12, patients receiving OG therapy had more patients with investigator global evaluation score improvements of at least two grades and more decreases in both inflammatory and noninflammatory lesions from baseline[2].
In vivo activity of Olumacostat glasaretil has been demonstrated in animal models, where topical application significantly reduces hamster ear sebaceous gland size. As a prodrug of the ACC inhibitor TOFA, it is designed to enhance delivery in vivo, and topical application of Olumacostat glasaretil, but not TOFA, produces significant effects on sebaceous glands. This demonstrates the improved in vivo efficacy of the prodrug formulation. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (cell-free) assay for Olumacostat glasaretil involves measuring its inhibitory activity against acetyl coenzyme A carboxylase (ACC) in cell-free systems. These assays typically use purified ACC enzyme and measure the conversion of acetyl-CoA to malonyl-CoA in the presence of the compound. The inhibitory potency (IC50) is determined by assessing the reduction in enzyme activity. As a prodrug, the active metabolite TOFA is also evaluated in these assays to confirm ACC inhibition.
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| Cell Assay |
Primary human sebocytes are grown to confluence in 96-well plates in sebocyte growth medium and stimulated with 1 μM human insulin and 1 μM liver X receptor (LXR) agonist T0901317 in the presence of increasing concentrations of TOFA or olumacostat glasaretil in culture medium containing 0.1% DMSO. After 24 hours, stimulation/treatment medium is removed and test articles are reapplied in labeling medium containing [14C]-acetate. Following an additional 16 hours, cells are harvested using trypsin/EDTA. Lipid extracts are prepared and the amount of [14C]-acetate incorporation is determined by liquid scintillation as a measure of de novo fatty acid synthesis[1].
In vitro cellular assays for Olumacostat glasaretil are performed using primary human sebocytes or transformed sebocyte cell lines. These assays measure de novo lipid synthesis by incorporating radiolabeled acetate or other precursors into cellular lipids. The compound's ability to inhibit ACC activity in intact cells is assessed by measuring the reduction in fatty acid synthesis. These assays demonstrate the cellular activity of the prodrug and its conversion to the active ACC inhibitor TOFA. |
| Animal Protocol |
In vivo animal studies for Olumacostat glasaretil are conducted in hamster models, where the compound is applied topically to assess its effects on sebaceous gland size. The hamster ear model is a well-established system for evaluating compounds that modulate sebaceous gland function. Topical application of Olumacostat glasaretil significantly reduces sebaceous gland size, demonstrating its in vivo efficacy. These studies also evaluate the compound's local tolerability and potential for systemic absorption.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Olumacostat glasaretil are optimized for topical delivery, with the prodrug designed to enhance penetration into the skin and sebaceous glands. Following topical application, the compound is converted to its active metabolite, TOFA, which exerts the ACC inhibitory effect. Systemic absorption is minimal, reducing the potential for off-target effects. The pharmacokinetic profile is characterized by high local concentrations in the target tissue with low systemic exposure.
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| Toxicity/Toxicokinetics |
Toxicology studies of Olumacostat glasaretil have been conducted to support its clinical development for acne vulgaris. These studies include local tolerance assessments following topical application, as well as systemic toxicity evaluations. The compound is generally well-tolerated in preclinical studies, with minimal systemic toxicity due to its limited absorption. Skin irritation and sensitization potential are also evaluated as part of the toxicology program.
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| References |
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| Additional Infomation |
Olumacostat glasaretil has been used in trials investigating the treatment of acne vulgaris.
Olumacostat glasaretil is a prodrug of the ACC inhibitor TOFA, designed for the topical treatment of acne vulgaris. It has been investigated in clinical trials for its ability to reduce sebum production and improve acne lesions. The compound represents a novel approach to acne therapy by targeting the underlying lipid synthesis pathway in sebocytes. Its development highlights the potential of ACC inhibitors for dermatological indications. |
| Molecular Formula |
C26H43NO7
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|---|---|
| Molecular Weight |
481.63
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| Exact Mass |
481.303
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| Elemental Analysis |
C, 64.84; H, 9.00; N, 2.91; O, 23.25
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| CAS # |
1261491-89-7
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| PubChem CID |
89497391
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| Appearance |
White to light yellow solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
583.9±50.0 °C at 760 mmHg
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| Flash Point |
307.0±30.1 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.485
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| LogP |
7.72
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
22
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| Heavy Atom Count |
34
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| Complexity |
569
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C1=C([H])C([H])=C(C(=O)OC([H])([H])C(N(C([H])([H])[H])C([H])([H])C(=O)OC([H])([H])C([H])([H])[H])=O)O1)C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H]
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| InChi Key |
FYJLDICZGDFWKP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H43NO7/c1-4-6-7-8-9-10-11-12-13-14-15-16-19-32-25-18-17-22(34-25)26(30)33-21-23(28)27(3)20-24(29)31-5-2/h17-18H,4-16,19-21H2,1-3H3
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| Chemical Name |
[2-[(2-ethoxy-2-oxoethyl)-methylamino]-2-oxoethyl] 5-tetradecoxyfuran-2-carboxylate
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| Synonyms |
DRM-01B DRM01B Olumacostat glasaretil
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~259.54 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.08 mg/mL (4.32 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0763 mL | 10.3814 mL | 20.7628 mL | |
| 5 mM | 0.4153 mL | 2.0763 mL | 4.1526 mL | |
| 10 mM | 0.2076 mL | 1.0381 mL | 2.0763 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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