| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
| 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].
|
|---|---|
| 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 |
|
| Additional Infomation |
Acoramidis is a potent, highly selective, orally bioavailable transthyretin (TTR) stabilizer with potential disease-modifying activity. Upon oral administration, acoramidis binds to and stabilizes transthyretin (TTR), thereby preventing tetramer dissociation into monomers. This prevents misfolding of the TTR protein and inhibits the formation of TTR amyloid fibrils and the subsequent deposition of these insoluble protein clusters in the heart and peripheral nerves. TTR is a 127 amino acid transport protein for thyroxine and retinol and is secreted by the liver into the blood. The accumulation of TTR amyloid fibrils may result in thickening and stiffening of the ventricular wall, leading to heart failure.
Drug Indication Treatment of transthyretin amyloidosis (ATTR) |
| Molecular Formula |
C15H17FN2O3
|
|---|---|
| Molecular Weight |
292.305487394333
|
| Exact Mass |
292.122
|
| CAS # |
1446711-81-4
|
| Related CAS # |
Acoramidis hydrochloride;2242751-53-5
|
| PubChem CID |
71464713
|
| Appearance |
White to off-white solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
542.5±50.0 °C at 760 mmHg
|
| Flash Point |
281.9±30.1 °C
|
| Vapour Pressure |
0.0±1.5 mmHg at 25°C
|
| Index of Refraction |
1.579
|
| LogP |
3.73
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
21
|
| Complexity |
356
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
WBFUHHBPNXWNCC-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C15H17FN2O3/c1-9-12(10(2)18-17-9)4-3-7-21-14-8-11(15(19)20)5-6-13(14)16/h5-6,8H,3-4,7H2,1-2H3,(H,17,18)(H,19,20)
|
| Chemical Name |
3-[3-(3,5-dimethyl-1H-pyrazol-4-yl)propoxy]-4-fluorobenzoic acid
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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 | 3.4210 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
