Size | Price | |
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10mg | ||
25mg | ||
50mg | ||
100mg |
ln Vitro |
Similar to how it stabilizes V122I- and WT-TTR, Acoramidis (AG10, 0.1-10 μM, TTR ∼5 μM) is likewise more effective than it is at stabilizing WT and mutant TTR in whole serum [1]. Between 10 and 100 μM, Acoramidis (AG10) raises mitochondrial QO2 in a concentration-dependent manner [3]. Acoramidis (AG10) exhibits little inhibition of two frequently encountered off-targets in drug discovery: several cytochrome P450 isoenzymes (IC50 > 50 µM) (low toxicity) and the potassium channel hERG (IC50 > 100 µM) [1].
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Cell Assay |
Western blot analysis[1].
Cell Types: human serum (TTR ∼5 µM). Tested Concentrations: 0.1 and 10 μM. Incubation Duration: 72 hrs (hours). Experimental Results: More effective than Famidy in stabilizing TTR. AG10 at a concentration of 10 µM stabilizes almost all TTRs in serum. |
Animal Protocol |
Animal/Disease Models: Wistar rat[1].
Doses: 50 mg/kg/d (toxicity analysis). Route of Administration: Orally administered one time/day for 28 days. Experimental Results: Plasma Cmax of AG10-treated animals was shown to be approximately 40 µM, and histopathological evaluation of liver, kidney, heart, spleen, thymus, and lungs demonstrated no evidence of pathological processes. |
References |
[1]. Sravan C Penchala, et al. AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy-associated V122I transthyretin. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9992-7.
[2]. Jonathan C Fox, et al. First-in-Human Study of AG10, a Novel, Oral, Specific, Selective, and Potent Transthyretin Stabilizer for the Treatment of Transthyretin Amyloidosis: A Phase 1 Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Adult Volunteers. Clin Pharmacol Drug Dev. 2020 Jan;9(1):115-129. [3]. Stephen P Soltoff, et al. Evidence that tyrphostins AG10 and AG18 are mitochondrial uncouplers that alter phosphorylation-dependent cell signaling. J Biol Chem. 2004 Mar 19;279(12):10910-8. |
Molecular Formula |
C15H17FN2O3
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Molecular Weight |
292.305487394333
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CAS # |
1446711-81-4
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Related CAS # |
Acoramidis hydrochloride;2242751-53-5
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SMILES |
FC1=CC=C(C(=O)O)C=C1OCCCC1C(C)=NNC=1C
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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 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.) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 3.4210 mL | 17.1051 mL | 34.2103 mL | |
5 mM | 0.6842 mL | 3.4210 mL | 6.8421 mL | |
10 mM | 0.3421 mL | 1.7105 mL | 3.4210 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.