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Identification
NameN,N-dimethylarginine
Accession NumberDB01686  (EXPT01101)
Typesmall molecule
Groupsexperimental
Description

Asymmetric dimethylarginine (ADMA) is a naturally occurring chemical found in blood plasma. It is a metabolic by-product of continual protein modification processes in the cytoplasm of all human cells. It is closely related to L-arginine, a conditionally-essential amino acid. ADMA interferes with L-arginine in the production of nitric oxide, a key chemical to endothelial and hence cardiovascular health. [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
Asymmetric dimethylarginineNot AvailableNot Available
Dimethyl-l-arginineNot AvailableNot Available
Guanidino-n,n-dimethylarginineNot AvailableNot Available
N(5)-((Dimethylamino)iminomethyl)-L-ornithineNot AvailableNot Available
N(5)-[(dimethylamino)(imino)methyl]-L-ornithineNot AvailableNot Available
N(g)-dimethylarginineNot AvailableNot Available
N(g),N(g)-dimethyl-l-arginineNot AvailableNot Available
N(g),N(g)-dimethylarginineNot AvailableNot Available
N(G1),N(G1)-DimethylarginineNot AvailableNot Available
N(omega),N(omega)-dimethyl-l-arginineNot AvailableNot Available
NG,NG-dimethyl-l-arginineNot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
Categories
CAS number102783-24-4
WeightAverage: 202.2541
Monoisotopic: 202.14297584
Chemical FormulaC8H18N4O2
InChI KeyYDGMGEXADBMOMJ-LURJTMIESA-N
InChI
InChI=1S/C8H18N4O2/c1-12(2)8(10)11-5-3-4-6(9)7(13)14/h6H,3-5,9H2,1-2H3,(H2,10,11)(H,13,14)/t6-/m0/s1
IUPAC Name
(2S)-2-amino-5-[(E)-[amino(dimethylamino)methylidene]amino]pentanoic acid
SMILES
N[C@@H](CCC\N=C(/N)N(C)C)C(O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentAlpha Amino Acids and Derivatives
Alternative parentsAmino Fatty Acids; Tertiary Amines; Guanidines; Amidines; Enolates; Polyamines; Carboxylic Acids; Monoalkylamines
Substituentsguanidine; tertiary amine; carboxylic acid; enolate; amidine; polyamine; primary amine; amine; primary aliphatic amine; organonitrogen compound
Classification descriptionThis compound belongs to the alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
Pharmacology
IndicationNot Available
PharmacodynamicsAsymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is formed by methylation of arginine residues in proteins and released after proteolysis. In this reaction, S-adenosylmethionine is methyldonor and S-adenosylhomocysteine the demethylated product. ADMA and homocysteine are thus biochemically linked. Both plasma homocysteine and ADMA concentrations are increased in patients with renal dysfunction, probably as a result of an impairment in their metabolic, but not urinary, clearance. Hyperhomocysteinemia has been associated with an increased risk of cardiovascular disease in end-stage renal disease, especially in patients without malnutrition and inflammation. Also, plasma ADMA levels have been associated with cardiovascular disease in renal failure patients. Both homocysteine and ADMA are thought to mediate their adverse vascular effects by impairing endothelial, nitric oxide-dependent function resulting in decreased vasodilatation, increased smooth muscle cell proliferation, platelet dysfunction and increased monocyte adhesion.
Mechanism of actionNot Available
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.8076
Blood Brain Barrier - 0.57
Caco-2 permeable - 0.6688
P-glycoprotein substrate Substrate 0.6229
P-glycoprotein inhibitor I Non-inhibitor 0.9691
P-glycoprotein inhibitor II Non-inhibitor 0.8965
Renal organic cation transporter Non-inhibitor 0.7389
CYP450 2C9 substrate Non-substrate 0.8266
CYP450 2D6 substrate Non-substrate 0.7315
CYP450 3A4 substrate Non-substrate 0.6171
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9242
CYP450 2C19 substrate Non-inhibitor 0.93
CYP450 3A4 substrate Non-inhibitor 0.8462
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9962
Ames test Non AMES toxic 0.6415
Carcinogenicity Non-carcinogens 0.8837
Biodegradation Not ready biodegradable 0.7658
Rat acute toxicity 2.0460 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.944
hERG inhibition (predictor II) Non-inhibitor 0.9228
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
water solubility6.77e+00 g/lALOGPS
logP-3.1ALOGPS
logP-2.7ChemAxon
logS-1.5ALOGPS
pKa (strongest acidic)2.54ChemAxon
pKa (strongest basic)12.34ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count6ChemAxon
hydrogen donor count3ChemAxon
polar surface area104.94ChemAxon
rotatable bond count5ChemAxon
refractivity53.7ChemAxon
polarizability22.19ChemAxon
number of rings0ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. van Guldener C, Nanayakkara PW, Stehouwer CD: Review: Homocysteine and asymmetric dimethylarginine (ADMA): biochemically linked but differently related to vascular disease in chronic kidney disease. Clin Chem Lab Med. 2007 Oct 15;. Pubmed
External Links
ResourceLink
KEGG CompoundC03626
PubChem Compound123831
PubChem Substance46508091
ChemSpider487
ChEBI17929
ChEMBL
HETDA2
WikipediaAsymmetric_dimethylarginine
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Nitric oxide synthase, inducible

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Nitric oxide synthase, inducible P35228 Details

References:

  1. van Guldener C, Nanayakkara PW, Stehouwer CD: Review: Homocysteine and asymmetric dimethylarginine (ADMA): biochemically linked but differently related to vascular disease in chronic kidney disease. Clin Chem Lab Med. 2007 Oct 15;. Pubmed

2. Nitric oxide synthase, endothelial

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Nitric oxide synthase, endothelial P29474 Details

References:

  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:15