| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
As an endogenous index of renal function, SDMA is a structural isomer of asymmetric dimethylarginine, a cardiovascular risk factor. SDMA is a rival for arginine transport but does not directly block NOS. A promising endogenous measure of glomerular filtration rate, SDMA is mostly excreted by the kidneys [1]. While SDMA has no effect on the protein expression of NOS, it dose-dependently suppresses the production of NO in intact endothelial cells [1]. Through the activation of NF-κB and subsequent upregulation of IL-6 and TNF-α production, SDMA contributes to the inflammatory process associated with chronic kidney disease [2].
|
|---|---|
| ln Vivo |
Both serum and plasma samples of SDMA exhibit good stability, and the assay performs exceptionally well analytically. While SDMA stays constant in dogs who are not affected, it increases in dogs that are afflicted as the disease progresses and is closely correlated with increases in sCr and decreases in GFR [3]. After four weeks, mice receiving a chronic SDMA infusion showed a substantial rise in SDMA levels but no change in GFR. There were no histological alterations seen, particularly in terms of fibrosis or the expression of nitric oxide synthase in endothelial cells. Systolic blood pressure and ejection fraction are unaffected by SDMA [4].
|
| ADME/Pharmacokinetics |
Metabolism / Metabolites
Uremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces. |
| Toxicity/Toxicokinetics |
Toxicity Summary
Uremic toxins such as symmetric dimethylarginine are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (A7868). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (A7869). |
| References |
|
| Additional Infomation |
N(omega),N'(omega)-dimethyl-L-arginine is a L-arginine derivative having two methyl groups at the N(omega)- and N'(omega)-positions It has a role as an EC 1.14.13.39 (nitric oxide synthase) inhibitor. It is a member of guanidines, a non-proteinogenic L-alpha-amino acid, a L-arginine derivative and a dimethylarginine. It is a conjugate base of a N(omega),N('omega)-dimethyl-L-argininium(1+). It is a tautomer of a N(omega),N'(omega)-dimethyl-L-arginine zwitterion.
Symmetric Dimethylarginine is a dimethylated derivative of L-arginine where the two methyl groups are attached to arginine in a symmetrical configuration. Symmetric dimethylarginine (SDMA) is formed when S-adenosylmethionine protein N-methyltransferases transfer one methyl group from S-adenosylmethionine to each of the two guanidine nitrogen groups of a single arginine residue in a protein. SDMA is released when the protein is degraded. SDMA doesn't bind nitric oxide synthase (NOS) but may noncompetitivelty inhibit nitric oxide (NO) synthesis by reducing L-arginine availability; it also may play a role in the modulation of cardiovascular homeostasis and renal function. Symmetric dimethylarginine is a uremic toxin. Uremic toxins can be subdivided into three major groups based upon their chemical and physical characteristics: 1) small, water-soluble, non-protein-bound compounds, such as urea; 2) small, lipid-soluble and/or protein-bound compounds, such as the phenols and 3) larger so-called middle-molecules, such as beta2-microglobulin. Chronic exposure of uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease. Symmetric dimethylarginine (SDMA) is an endogenously produced inhibitor of nitric oxide synthase (EC-Number 1.14.13.39). However, elevated levels of SDMA occur in patients with vascular disease, especially suffering end-stage renal disease. (A3290). |
| Molecular Formula |
C8H18N4O2
|
|---|---|
| Molecular Weight |
202.25412
|
| Exact Mass |
202.143
|
| CAS # |
30344-00-4
|
| PubChem CID |
169148
|
| Appearance |
White to off-white solid powder
|
| Density |
1.22g/cm3
|
| Boiling Point |
367.7ºC at 760mmHg
|
| Flash Point |
176.2ºC
|
| Index of Refraction |
1.54
|
| LogP |
0.455
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
14
|
| Complexity |
206
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
N[C@@H](CCCN/C(NC)=N/C)C(O)=O
|
| InChi Key |
HVPFXCBJHIIJGS-LURJTMIESA-N
|
| InChi Code |
InChI=1S/C8H18N4O2/c1-10-8(11-2)12-5-3-4-6(9)7(13)14/h6H,3-5,9H2,1-2H3,(H,13,14)(H2,10,11,12)/t6-/m0/s1
|
| Chemical Name |
(2S)-2-amino-5-[(N,N'-dimethylcarbamimidoyl)amino]pentanoic 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) |
DMSO : ~67.5 mg/mL (~333.75 mM)
H2O : ~50 mg/mL (~247.22 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (12.36 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (12.36 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: 2.5 mg/mL (12.36 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: 120 mg/mL (593.33 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.9444 mL | 24.7219 mL | 49.4438 mL | |
| 5 mM | 0.9889 mL | 4.9444 mL | 9.8888 mL | |
| 10 mM | 0.4944 mL | 2.4722 mL | 4.9444 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
