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| Targets |
The primary target of (R)-Aminocarnitine TFA is the enzyme carnitine palmitoyltransferase (CPT), specifically the CPT1 isoform, which resides on the outer mitochondrial membrane. CPT1 catalyzes the rate-limiting step in fatty acid oxidation: the transfer of a long-chain fatty acyl group from acyl-CoA to carnitine, forming acylcarnitine. (R)-Aminocarnitine is a carnitine analog and acts as a competitive inhibitor of CPT1, preventing the binding of carnitine to the enzyme. By inhibiting CPT1, (R)-Aminocarnitine blocks the entry of long-chain fatty acids into the mitochondria, thereby reducing the rate of beta-oxidation and energy production from fatty acids. This mechanism forces cells to rely more heavily on glucose metabolism, which has implications for conditions characterized by excessive fatty acid oxidation, such as diabetes-induced hyperglycemia and ketosis. Unlike the S-enantiomer, the (R)-enantiomer is the active isomer for CPT inhibition.
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| ln Vitro |
In vitro studies have demonstrated that (R)-Aminocarnitine (Emeriamine) TFA is a potent inhibitor of fatty acid oxidation. It directly inhibits CPT1 activity in isolated mitochondria and in cell lysates. The compound reduces the conversion of palmitoyl-CoA to palmitoylcarnitine, a key step in the beta-oxidation pathway. This results in decreased production of acetyl-CoA from fatty acids, leading to a reduction in ketone body synthesis. In primary hepatocytes, treatment with (R)-Aminocarnitine TFA reduces fatty acid oxidation rates and lowers glucose output, which is beneficial in hyperglycemic conditions. The IC50 for CPT1 inhibition is typically in the low micromolar range, though specific values may vary depending on the assay conditions and the source of the enzyme. The compound has no significant direct effect on mitochondrial respiration in the absence of fatty acid substrates. It has also been studied in cardiac myocytes, where inhibition of fatty acid oxidation can shift energy substrate utilization toward glucose, a phenomenon known as "metabolic modulation," which may have protective effects in ischemic heart disease.
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| ln Vivo |
The in vivo activity of (R)-Aminocarnitine has been demonstrated in animal models of diabetes and obesity. In diabetic rodents (e.g., streptozotocin-induced diabetic rats or genetically obese Zucker rats), administration of (R)-Aminocarnitine reduces hyperglycemia (high blood glucose) and lowers ketosis (elevated ketone bodies). By inhibiting hepatic fatty acid oxidation, the compound reduces the availability of acetyl-CoA and NADH, which are necessary for gluconeogenesis. This leads to a decrease in endogenous glucose production by the liver. The compound also reduces plasma free fatty acid levels and improves insulin sensitivity in some models. (R)-Aminocarnitine has been shown to decrease whole-body fatty acid oxidation and increase glucose oxidation, as measured by indirect calorimetry. In models of diabetic ketoacidosis, it has been effective in lowering blood ketone levels. These effects are consistent with its mechanism of action as a CPT1 inhibitor. The compound has not been advanced to clinical trials as a drug, however, and its in vivo activity is primarily studied as a research tool to validate the metabolic effects of CPT1 inhibition.
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| Enzyme Assay |
The specific experimental protocols for assessing the inhibitory activity of (R)-Aminocarnitine TFA on carnitine palmitoyltransferase (CPT) are well-established. A standard protocol for a cell-free (in vitro) CPT1 assay involves: (1) Isolating mitochondria from rat liver or heart using differential centrifugation. (2) Preparing a reaction mixture containing 40 mM Tris-HCl (pH 8.0), 60 mM KCl, 1 mM EDTA, 1 mM DTT, 1 mM KCN (to inhibit electron transport chain), 2 uM rotenone (complex I inhibitor), 0.1% fatty-acid free BSA, 50 uM palmitoyl-CoA, and varying concentrations of (R)-Aminocarnitine TFA (0-100 uM). (3) The reaction is initiated by adding L-[3H]carnitine (final concentration ~0.5-1 uCi/assay) along with unlabeled carnitine to achieve a final carnitine concentration of 200-500 uM. (4) The reaction is allowed to proceed at 30degC for 5-10 minutes (within the linear range of the assay). (5) The reaction is terminated by adding 1.2 mL of ice-cold 4% perchloric acid. (6) The [3H]palmitoylcarnitine product is extracted into butanol (1 mL) and the radioactivity is measured by liquid scintillation counting. (7) The IC50 is calculated by plotting the percent inhibition vs. the log concentration of the inhibitor.
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| Cell Assay |
Cellular in vitro assays for (R)-Aminocarnitine TFA typically focus on measuring fatty acid oxidation rates in cultured cells, such as primary hepatocytes, myotubes, or cardiomyocytes. A standard protocol: (1) Seed cells (e.g., HepG2 human hepatoma cells or rat primary hepatocytes) onto 24-well plates and culture to confluence. (2) The day before the assay, replace the medium with serum-free medium to reduce background fatty acids. (3) For the assay, prepare a medium containing 0.5-1.0 uCi/mL of [9,10-3H]-palmitic acid or [1-14C]-palmitic acid complexed to fatty-acid free BSA (e.g., 100 uM palmitate with a 5:1 molar ratio of BSA:palmitate). (4) Add (R)-Aminocarnitine TFA (e.g., 1-100 uM) to the wells. (5) Incubate the cells for 2-4 hours at 37degC. (6) Collect the culture medium and transfer it to a tube containing 10% trichloroacetic acid (TCA) to precipitate any remaining labeled fatty acids. (7) For the 3H-labeled assay, collect the 3H2O (a product of beta-oxidation) by separating the water phase via evaporation or by using a biphasic extraction system. For 14C-labeled assay, trap the 14CO2 produced by placing a filter paper soaked with 1M NaOH or hyamine hydroxide inside the sealed culture vessel. (8) Measure the radioactivity (3H in water or 14C in CO2) by liquid scintillation counting. (9) Fatty acid oxidation rate is calculated as pmol of fatty acid oxidized per hour per mg of protein.
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| Animal Protocol |
A standard in vivo animal protocol for testing the efficacy of (R)-Aminocarnitine TFA in a model of hyperglycemia and ketosis (e.g., streptozotocin-induced diabetic rats) is as follows: (1) Induce diabetes in male Sprague-Dawley rats (200-250g) by a single intraperitoneal injection of streptozotocin (STZ, 60 mg/kg in 0.1M citrate buffer, pH 4.5). (2) Measure blood glucose levels 48 hours post-injection to confirm diabetes (e.g., >250 mg/dL). (3) On day 7 post-STZ, fast the animals overnight (12-16 hours). (4) The next morning, prepare (R)-Aminocarnitine TFA as a solution (e.g., in sterile water or saline). (5) Administer the compound via an appropriate route (e.g., intraperitoneal injection (IP) at a dose of 5-50 mg/kg, or oral gavage). (6) Collect blood samples from the tail vein at baseline (0) and at multiple time points (e.g., 1, 2, 4, 6 hours) post-dose. (7) Measure blood glucose using a glucometer. (8) Measure plasma beta-hydroxybutyrate (a ketone body) using a colorimetric assay kit. (9) Euthanize animals at the end of the experiment (e.g., 6 hours) and harvest liver for measurement of CPT1 activity ex vivo. (10) Compare the blood glucose and ketone levels in the treated group to those in a vehicle-treated control group to determine the efficacy.
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| ADME/Pharmacokinetics |
There are no published pharmacokinetic data for (R)-Aminocarnitine TFA, as it is not a drug candidate. As a small molecule (MW 274.24), it is likely to be absorbed following oral or intraperitoneal administration, but no formal ADME studies have been conducted. The compound is soluble in water and polar organic solvents due to the TFA counterion. The trifluoroacetic acid (TFA) salt form is often used to improve the compound's crystallinity and stability. The free base (R)-Aminocarnitine (also known as Emeriamine) would be the active species. In cells, as a carnitine analog, it is likely taken up by the carnitine transporter (OCTN2) on the cell membrane, which is the same transporter that mediates cellular uptake of L-carnitine. This suggests that (R)-Aminocarnitine could concentrate in tissues expressing high levels of OCTN2, such as the liver, heart, and skeletal muscle. It is likely metabolized to some extent, but specific metabolites have not been described. Excretion is expected to be primarily renal. Storage conditions: powder at -20degC for up to 3 years, and in solution (e.g., DMSO) at -80degC for 6 months.
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| Toxicity/Toxicokinetics |
Specific toxicological data for (R)-Aminocarnitine TFA have not been published, as it is a research compound and not a therapeutic agent. However, the mechanism of action (inhibition of fatty acid oxidation) raises potential toxicity concerns that are relevant to drug development. Chronic inhibition of fatty acid oxidation can lead to lipid accumulation in non-adipose tissues (steatosis), particularly in the liver (hepatic steatosis) and heart (cardiac lipidosis), because fatty acids cannot be oxidized for energy and are instead esterified and stored as triglycerides. In animal studies with other CPT1 inhibitors, high doses or long-term treatment have been associated with liver toxicity, cardiac dysfunction, and muscle weakness. Moreover, inhibiting fatty acid oxidation can lead to hypoglycemia (low blood glucose) in the fasted state, as the body becomes unable to switch from glucose to fatty acid oxidation for energy. For this reason, such compounds are contraindicated in situations of low glucose availability. (R)-Aminocarnitine TFA is intended for research use only, and not for human or veterinary use. No clinical trials have been conducted, and no regulatory approvals exist for this compound.
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| References | |
| Additional Infomation |
(R)-Aminocarnitine TFA (Emeriamine TFA) is a valuable tool for metabolic research, allowing investigators to dissect the role of fatty acid oxidation in various physiological and pathological contexts. It is particularly useful for studying the metabolic shift from fatty acid to glucose oxidation (a concept known as "metabolic modulation") as a potential therapeutic strategy for ischemic heart disease, heart failure, and diabetic hyperglycemia. The (R)-enantiomer is the active isomer; the (S)-enantiomer is significantly less potent or inactive. The compound is often compared to other CPT1 inhibitors such as etomoxir, oxfenicine, and perhexiline, each with different isoforms selectivity and safety profiles. Unlike etomoxir, which irreversibly inhibits CPT1, (R)-Aminocarnitine is a reversible competitive inhibitor. This reversible mechanism may offer a more controllable pharmacological effect. The compound is not a drug and is not approved by the FDA or EMA for any clinical indication. It has not been evaluated in clinical trials. Its use is confined to basic research into the pathogenesis of metabolic diseases and the validation of CPT1 as a drug target. There is no information regarding its solubility in other solvents beyond DMSO and water, though as a TFA salt, it is expected to be relatively soluble.
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| Molecular Formula |
C9H17F3N2O4
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| Molecular Weight |
274.24
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| Appearance |
Colorless to off-white solid powder
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| Synonyms |
Emeriamine TFA
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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 Note: (1). Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~150 mg/mL (~546.97 mM; with ultrasonication)
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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 | 3.6464 mL | 18.2322 mL | 36.4644 mL | |
| 5 mM | 0.7293 mL | 3.6464 mL | 7.2929 mL | |
| 10 mM | 0.3646 mL | 1.8232 mL | 3.6464 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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