| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
ALG-055009 is a potent and selective agonist of the thyroid hormone receptor beta (THR-beta). It exhibits an EC50 of 63 nM (0.063 microM) and is 5.7-fold selective over the THR-alpha subtype. By activating THR-beta, it mimics the lipid-lowering effects of thyroid hormones in the liver while avoiding the cardiac side effects associated with THR-alpha activation.
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| ln Vitro |
ALG-055009 is a potent THR-beta agonist with an EC50 of 63 nM in vitro. This activity is likely measured in a cell-based luciferase reporter assay where THR-beta activation drives expression of a luminescent reporter gene. Its 5.7-fold selectivity for THR-beta over THR-alpha is a key feature that reduces the risk of cardiotoxicity.
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| ln Vivo |
In vivo, ALG-055009 has shown efficacy in a high-fat diet rat model. At doses greater than 0.075 mg/kg, it reduces serum lipid levels. It also significantly increases hepatic gene expression of Dio1 and Me1, which are markers of THR-beta activation, at doses of 0.15 and 0.5 mg/kg. This data supports its development for treating dyslipidemia and MASH.
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| Enzyme Assay |
THR-beta agonist activity is typically measured using a cell-based reporter gene assay, not a cell-free binding assay. However, to measure binding affinity, a competitive binding assay using radiolabeled triiodothyronine (T3) and purified THR-beta ligand-binding domain (LBD) can be used. Procedure: The THR-beta LBD is incubated with 0.1 nM [125I]-T3 and varying concentrations of ALG-055009 (0.01 nM to 10 microM) in binding buffer for 4 hours at 4degC. Free radioligand is separated using a spin column or charcoal-dextran method. Bound radioactivity is counted in a gamma counter. The IC50 is calculated, and the Ki is derived using the Cheng-Prusoff equation.
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| Cell Assay |
The functional potency of ALG-055009 is assessed in a THR-beta reporter cell line. Procedure: HEK-293 cells are transiently or stably transfected with a plasmid encoding human THR-beta and a luciferase reporter gene under the control of a thyroid hormone response element (TRE). Cells are seeded in 96-well white plates (20,000 cells/well) and incubated for 24 hours. The medium is replaced with medium containing varying concentrations of ALG-055009 (0.01 nM to 10 microM) and incubated for 24 hours. The cells are then lysed, and luciferase activity is measured by adding a luciferin substrate and reading luminescence in a plate reader. The EC50 is calculated as the concentration that produces 50% of the maximal T3 response.
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| Animal Protocol |
The in vivo efficacy of ALG-055009 is evaluated in a high-fat diet (HFD)-induced hyperlipidemia rat model. Procedure: Male Sprague-Dawley rats are fed a HFD (60% kcal from fat) for 4 weeks to induce hyperlipidemia. The rats are then randomized into treatment groups (n=8). ALG-055009 is formulated in a vehicle (e.g., 0.5% methylcellulose) and administered orally once daily at doses of 0.01, 0.05, 0.1, and 0.5 mg/kg for 14 days. Blood samples are collected on days 0, 7, and 14 for lipid panel analysis (total cholesterol, triglycerides, LDL-C, HDL-C). At the end of the study, liver tissue is collected for qRT-PCR analysis of THR-beta target genes, including Dio1 and Me1.
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| ADME/Pharmacokinetics |
ALG-055009 is orally bioavailable and active in rats. Pharmacokinetic parameters have not been detailed in the search results, but as an orally active compound being developed for MASH, it is expected to have favorable absorption and a half-life suitable for once-daily dosing. The molecular weight is 425.23, and it likely has high passive permeability due to its lipophilic nature. It is expected to have extensive first-pass metabolism in the liver, which is typical for thyroid hormone agonists.
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| Toxicity/Toxicokinetics |
Specific toxicity data for ALG-055009 is not provided. As a selective THR-beta agonist, the primary safety concern is potential off-target activation of THR-alpha in the heart, which can cause tachycardia and arrhythmias. Its 5.7-fold selectivity is designed to mitigate this risk. However, no long-term toxicology studies in higher species have been reported in the search results. It is an investigational compound, and standard safety pharmacology (including hERG) and toxicology studies are likely ongoing.
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| References | |
| Additional Infomation |
ALG-055009 is an investigational drug being developed for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), a severe form of fatty liver disease, and hyperlipidemia. The selective activation of THR-beta has emerged as a promising therapeutic strategy because it promotes the clearance of lipids from the liver without causing the cardiac strain associated with non-selective thyroid hormone mimetics. This compound represents a next-generation thyroid hormone mimetic that offers a potentially safer profile than earlier non-selective compounds. This product is for research use only and is not an FDA-approved drug.
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| Molecular Formula |
C16H14CL2N6O4
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| Molecular Weight |
425.23
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| CAS # |
2542029-03-6
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| Appearance |
Typically exists as solids at room temperature
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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 | 2.3517 mL | 11.7583 mL | 23.5167 mL | |
| 5 mM | 0.4703 mL | 2.3517 mL | 4.7033 mL | |
| 10 mM | 0.2352 mL | 1.1758 mL | 2.3517 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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