Uremic toxin transporters (OAT3) and protein biosynthesis pathways. Argininic acid is an alpha-amino acid that is used in the biosynthesis of proteins. It contains a guanidino group that confers strong basicity. Argininic acid is a uremic toxin that is actively transported into the kidneys via organic ion transporters, especially OAT3.

Arginine comprises α-amino group, α-carboxylic acid group and a side chain formed of a 3-carbon aliphatic straight chain ending with a guanidine group. In humans, arginine is classed as a semi-essential amino acid or a conditionally essential amino acid, depending on the individual's developmental stage and health situation.

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In vitro, Argininic acid functions as a proteinogenic amino acid used in protein biosynthesis. It contains an alpha-amino group, an alpha-carboxylic acid group, and a side chain consisting of a 3-carbon aliphatic straight chain ending in a guanidino group. As a uremic toxin, it is studied for its role in kidney disease and its transport by organic ion transporters. The compound is used as a research tool to study amino acid metabolism and uremic toxicity.

In vivo, Argininic acid is a uremic toxin that accumulates in the blood of patients with kidney disease. It is actively transported into the kidneys via organic ion transporters, especially OAT3. The compound is studied in animal models of kidney disease to understand its role in uremic toxicity and its effects on renal function.

In vitro transporter assays for Argininic acid measure its uptake by organic ion transporters such as OAT3. The assay uses cells expressing recombinant OAT3 and radiolabeled Argininic acid. Cells are incubated with varying concentrations of the compound, and uptake is measured by scintillation counting. Kinetic parameters (Km, Vmax) are calculated from uptake curves.

In vitro cell-based assays for Argininic acid use kidney cell lines or primary renal cells. Cells are cultured in appropriate media and treated with varying concentrations of the compound (typically 0.1-10 mM) for 1-24 hours. Cellular effects measured include cell viability, oxidative stress markers, and changes in gene expression. The compound's effects on organic ion transporter expression and function can also be assessed.

In vivo animal studies for Argininic acid are conducted in rodent models of kidney disease. Animals are administered the compound via intravenous or intraperitoneal injection at doses of 10-100 mg/kg. Blood and urine samples are collected for analysis of argininic acid levels and kidney function markers. Kidney tissue is collected for histology and biomarker analysis.

Metabolism / Metabolites
Uremic toxins often accumulate in the blood due to overeating or poor kidney filtration. Most uremic toxins are metabolic waste products that are normally excreted through urine or feces.

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Pharmacokinetic properties of Argininic acid are characteristic of amino acids. With a molecular weight of 175.19 and a molecular formula of C6H13N3O3, the compound is water-soluble. It is actively transported into the kidneys via organic ion transporters. Standard pharmacokinetic parameters (Cmax, Tmax, AUC, half-life, clearance) can be determined in preclinical species.

Toxicity Summary
Uremic toxins (such as arginine) are actively transported to the kidneys via organic ion transporters, particularly OAT3. Elevated uremic toxin levels can stimulate the production of reactive oxygen species (ROS). This appears to be mediated by the direct binding of uremic toxins to or inhibition of NADPH oxidases, particularly NOX4, which is abundant in the kidneys and heart (A7868). ROS can induce a variety of different DNA methyltransferases (DNMTs) involved in the silencing of a protein called KLOTHO. KLOTHO has been shown to play an important role in anti-aging, mineral metabolism, and vitamin D metabolism. Multiple studies have shown that during acute or chronic kidney disease, the mRNA and protein levels of KLOTHO are reduced due to elevated local ROS levels (A7869).

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Argininic acid is a naturally occurring amino acid and uremic toxin. Standard safety precautions for handling chemical compounds apply. The compound is not approved for clinical use as a therapeutic agent.

Arginine is a nitrogen- and oxygen-containing organic compound whose function is related to δ-amino acids. Arginine is a uremic toxin. Based on chemical and physical properties, uremic toxins can be classified into three main categories: 1) small, water-soluble, non-protein-bound compounds, such as urea; 2) small, lipid-soluble and/or protein-bound compounds, such as phenols; and 3) larger, so-called medium-molecule compounds, such as β2-microglobulins. Long-term exposure to uremic toxins can lead to a variety of diseases, including kidney damage, chronic kidney disease, and cardiovascular disease. Hyperargininemia leads to the accumulation of arginine (AA) in tissues. Hyperargininemia is a congenital metabolic disorder of the urea cycle caused by a severe deficiency of hepatic arginase, resulting in elevated levels of arginine (Arg) and other guanidine compounds (GC) in tissues. Affected patients exhibit a neurological syndrome including varying degrees of intellectual disability, epilepsy, and progressive seizures; the pathophysiological mechanisms of which are far from being elucidated. Guanidine compounds can also accumulate in other pathological conditions, such as uremia and epilepsy, and some evidence supports the hypothesis that these compounds cause neurological dysfunctions specific to these diseases. The increase in these compounds is due to the inhibition of the arginase reaction, which activates secondary biochemical pathways. Therefore, arginine is converted to α-keto-α-guanidinovalerate via transamination, and this compound is further hydrogenated to form arachidonic acid (AA). (A3288)

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Argininic acid is a naturally occurring alpha-amino acid with a molecular formula of C6H13N3O3 and a molecular weight of 175.19. It is also known as (2S)-5-(diaminomethylideneamino)-2-hydroxypentanoic acid or L-5-guanidino-2-hydroxyvaleric acid. Argininic acid is a uremic toxin that is actively transported into the kidneys via organic ion transporters (especially OAT3). It is used as a research tool to study amino acid metabolism and uremic toxicity. Not approved for clinical use.

C6H13N3O3

175.18572

175.096

157-07-3

160437

Off-white to light yellow solid powder

1.46g/cm3

443.8ºC at 760 mmHg

222.2ºC

9.68E-10mmHg at 25°C

1.579

-1.7

4

4

5

12

177

1

C(C[C@@H](C(=O)O)O)CN=C(N)N

BMFMQGXDDJALKQ-BYPYZUCNSA-N

InChI=1S/C6H13N3O3/c7-6(8)9-3-1-2-4(10)5(11)12/h4,10H,1-3H2,(H,11,12)(H4,7,8,9)/t4-/m0/s1

(2S)-5-(diaminomethylideneamino)-2-hydroxypentanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)