| 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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| 250mg |
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| 500mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Corneal esterases (for hydrolysis); biological targets of lipoic acid (antioxidant pathways). Alpha-Lipoic Acid Choline Ester is a prodrug designed to deliver lipoic acid to the lens of the eye. It permeates the cornea, is hydrolyzed by corneal esterases, and releases biologically active lipoic acid. Lipoic acid acts as an antioxidant and may improve lens elasticity, which is relevant to the treatment of presbyopia.
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| ln Vitro |
6S,8S-Bis(3-methylthiopropanoyl) thiolesters of lipoic acid were synthesized with the carboxyl moiety of lipoate modified as methyl or water soluble choline esters. Evaluation on different cell lines in culture showed that they possessed modest antiproliferative activity. However, the 6-fold decrease in IC50 (from 270 to 45 microM) observed with the water soluble 6S,8S-bis(3-methylthiopropenoyl) thiolester dehydro derivative on a human epithelial prostate cancer cell line (DU145) argues in favor of 3-methylthiopropanoyl metabolites as endogenous growth regulatory (apoptogenic) compounds derived from methionine[1].
Alpha-Lipoic Acid Choline Ester has been shown to reduce protein disulfides and increase the elasticity of mouse lenses in vitro. It possesses modest antiproliferative activity in various cell lines, with a 6-fold decrease in IC50 observed for a water-soluble derivative on the DU145 human epithelial prostate cancer cell line. The compound's ability to deliver lipoic acid to target tissues has been characterized. |
| ln Vivo |
In vivo, Alpha-Lipoic Acid Choline Ester is being developed as an ophthalmic treatment for presbyopia. It is formulated as an eye drop solution applied twice daily. The compound has been shown to improve lens elasticity and restore accommodative function in preclinical models. Clinical studies have been conducted to evaluate its efficacy and safety in patients with presbyopia.
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| Enzyme Assay |
In vitro assays for Alpha-Lipoic Acid Choline Ester typically involve measuring its ability to reduce protein disulfides and increase lens elasticity. Mouse lenses are cultured and treated with the compound, and changes in lens stiffness or accommodative amplitude are measured. Cell-based assays may also be performed to assess antiproliferative activity. The compound's hydrolysis by corneal esterases can be studied using enzyme assays.
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| Cell Assay |
Cell-based assays for Alpha-Lipoic Acid Choline Ester have been performed using various cell lines, including the DU145 human epithelial prostate cancer cell line. Cells are treated with the compound at varying concentrations, and cell viability is assessed using standard assays such as MTT. The IC50 values are determined from dose-response curves. The compound's effects on protein disulfide reduction may also be assessed in cell culture.
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| Animal Protocol |
In vivo animal studies for Alpha-Lipoic Acid Choline Ester have been conducted in mouse models to evaluate its effects on lens elasticity and accommodative function. The compound is typically administered as eye drops, and lens stiffness or accommodative amplitude is measured. Dosing regimens vary, but the compound has been shown to be effective at improving lens function in preclinical models.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for Alpha-Lipoic Acid Choline Ester indicate that it is designed to permeate biological membranes through its cationic choline head group. The compound is hydrolyzed by corneal esterases and transformed into lipoic acid. It is formulated as an ophthalmic solution for topical application. Its molecular weight is 327.93. Detailed systemic PK parameters are not extensively documented.
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| Toxicity/Toxicokinetics |
Alpha-Lipoic Acid Choline Ester has been evaluated for safety in preclinical and clinical studies. It is formulated as an ophthalmic solution and is generally well-tolerated when applied topically. The compound is not approved for therapeutic use in many jurisdictions and is intended for research purposes. Standard safety precautions should be taken when handling the compound.
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| References |
[1]. Synthesis and effects of 3-methylthiopropanoyl thiolesters of lipoic acid, methional metabolite mimics. Bioorg Chem. 2006 Feb;34(1):49-58.
[2]. Geometrical isomerism of monounsaturated fatty acids: thiyl radical catalysis and influence of antioxidant vitamins. Free Radic Biol Med. 2002 Dec 15;33(12):1681-92. |
| Additional Infomation |
Sulfur radicals generated from thiols or disulfides can catalyze the cis-trans isomerization of various monounsaturated fatty acid methyl esters in homogeneous solutions. Similar results were obtained using α-lipoic acid and its reduced form. The effectiveness of the isomerization process in the presence of the most commonly used antioxidants was investigated. The sulfur radical scavenging capacity was found to increase in the following order: α-tocopherol < ascorbic acid < all-trans retinol. In addition, the cis-trans isomerization of fatty acid residues in dioleoylphosphatidylcholine multilayer vesicles by sulfur radicals in the presence or absence of various antioxidants was investigated in detail. The effect of the isomerization process on the phospholipid bilayer was tested by vesicle permeability measurements, and the results clearly showed that membranes containing trans fatty acids have properties intermediate between those formed by all-cis and saturated components. This study contributes to understanding the radical processes that can alter or protect the natural cis geometry of unsaturated lipids in cell membranes and reveals new roles of essential antioxidants. [2]
Alpha-Lipoic Acid Choline Ester (alpha-LACE, EV-06, UNR844) is a drug candidate for the treatment of presbyopia. It is a choline ester prodrug of lipoic acid designed to permeate the cornea and deliver active lipoic acid to the lens. The compound has been formulated as an ophthalmic solution for twice-daily application. It is not approved for clinical use in many countries and is available for research purposes. |
| Molecular Formula |
C13H26CLNO2S2
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|---|---|
| Molecular Weight |
327.93
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| Exact Mass |
327.109
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| Elemental Analysis |
C, 47.62; H, 7.99; Cl, 10.81; N, 4.27; O, 9.76; S, 19.55
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| CAS # |
1808266-58-1
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| Related CAS # |
1808266-58-1 (chloride);1258436-42-8 (bromide);1258436-41-7 (iodide);1258491-58-5 (cation);
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| PubChem CID |
92135660
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
19
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| Complexity |
254
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| Defined Atom Stereocenter Count |
1
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| SMILES |
[Cl-].S1[C@@H](CCS1)CCCCC(=O)OCC[N+](C)(C)C
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| InChi Key |
QMADNKDMPGZUKN-UTONKHPSSA-M
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| InChi Code |
InChI=1S/C13H26NO2S2.ClH/c1-14(2,3)9-10-16-13(15)7-5-4-6-12-8-11-17-18-12;/h12H,4-11H2,1-3H3;1H/q+1;/p-1/t12-;/m1./s1
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| Chemical Name |
(R)-2-((5-(1,2-dithiolan-3-yl)pentanoyl)oxy)-N,N,N-trimethylethan-1-aminium chloride
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| Synonyms |
alphaLACE; Alpha-Lipoic Acid Choline Ester; alpha LACE UNR844; UNR-844; EV-06; EV06; EV 06; alpha-LACE UNR 844; Lace chloride; Alpha-LipoicAcidCholineEster; (R)-2-((5-(1,2-Dithiolan-3-yl)pentanoyl)oxy)-N,N,N-trimethylethan-1-aminium chloride; Choline lipoate chloride; EV06 CHLORIDE; UNR844 CHLORIDE; EV-06 CHLORIDE;
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0494 mL | 15.2472 mL | 30.4943 mL | |
| 5 mM | 0.6099 mL | 3.0494 mL | 6.0989 mL | |
| 10 mM | 0.3049 mL | 1.5247 mL | 3.0494 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03809611 | Completed | Drug: UNR844-Cl Drug: Placebo |
Presbyopia | Novartis Pharmaceuticals | 2019-04-26 | Phase 2 |
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