Np mrd loader

Showing NP-Card for Fraxetin (NP0051447)

Jump To Section:
IdentificationSpectraBioTaxonomyChemoTaxonomyPhysical propertiesLinksReferencesXML
Record Information
Version2.0
Created at2022-04-27 22:48:39 UTC
Updated at2022-04-27 22:48:39 UTC
NP-MRD IDNP0051447
Secondary Accession NumbersNone
Natural Product Identification
Common NameFraxetin
DescriptionFraxetin belongs to the class of organic compounds known as 7,8-dihydroxycoumarins. These are coumarins bearing two hydroxyl groups at the C7- and C8-positions of the coumarin skeleton, respectively. Fraxetin is an extremely weak basic (essentially neutral) compound (based on its pKa). Fraxetin is found in Acer nikoense , Aesculus hippocastanum , Aesculus turbinata , Bupleurum fruticosum, Campanula dolomitica, Echites hirsuta, Fraxinus angustifolia, Fraxinus bungeana, Fraxinus chinensis , Fraxinus floribunda, Fraxinus japonica Seringe Blume , Fraxinus mandshurica, Fraxinus ornus , Fraxinus spp., Ginkgo biloba , Gochnatia argentina, Haplophyllum obtusifolium, Hydrangea vestita, Jatropha glandulifera, Rhododendron tomentosum, Lupinus angustifolius, Mondia whitei, Ocotea odorifera, Pelargonium sidoides , Peltogyne confertiflora, Protium heptaphyllum, Pterocaulon purpurascens, Salsola laricifolia, Santolina pinnata, Sarcandra glabra and Vestia lycioides. Fraxetin was first documented in 2001 (PMID: 11456117). A hydroxycoumarin that is 6-methoxycoumarin in which the hydrogens at positions 7 and 8 have been replaced by hydroxy groups (PMID: 12860476) (PMID: 15120578) (PMID: 15904944) (PMID: 15996779).
Structure
Thumb
MOL3D MOLSDFPDBSMILESInChI

MOL for NP0051447 (Fraxetin)


  Mrv1652310051709242D          

 15 16  0  0  0  0            999 V2000
    5.0013   -0.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4289    0.0000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7145   -0.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8579    0.0000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1434   -0.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.5724   -0.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7145   -1.2375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.5724   -1.2375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8579   -1.6500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1434   -1.2375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000   -1.6500    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.2868   -1.6500    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.8579   -2.4750    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.2868   -0.0000    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.4289   -1.6500    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  3  2  2  0  0  0  0
  5  2  1  0  0  0  0
  5  4  2  0  0  0  0
  6  4  1  0  0  0  0
  7  3  1  0  0  0  0
  8  6  2  0  0  0  0
  9  8  1  0  0  0  0
 10  5  1  0  0  0  0
 10  9  2  0  0  0  0
 11  7  2  0  0  0  0
 12  8  1  0  0  0  0
 13  9  1  0  0  0  0
 14  1  1  0  0  0  0
 14  6  1  0  0  0  0
 15  7  1  0  0  0  0
 15 10  1  0  0  0  0
M  END
Download

3D MOL for NP0051447 (Fraxetin)

     RDKit          3D

 23 24  0  0  0  0  0  0  0  0999 V2000
    3.1748   -1.7933   -0.6382 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8296   -0.4570   -0.4496 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.5377   -0.0110   -0.2190 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.4868   -0.9035   -0.1625 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8061   -0.4896    0.0649 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8449   -1.4100    0.1168 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.1020   -0.9123    0.3478 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3286    0.4406    0.5212 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.5164    0.8606    0.7343 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3248    1.2864    0.4665 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1082    0.8446    0.2471 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0557    1.7558    0.1923 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3530    3.0864    0.3735 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.2318    1.3200   -0.0365 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2474    2.2528   -0.0839 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.4343   -2.4046   -1.1575 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.4920   -2.2846    0.3226 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.0949   -1.8013   -1.2931 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.6382   -1.9659   -0.2949 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6058   -2.4464   -0.0254 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9176   -1.6200    0.3901 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2921    3.4139    0.5415 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.0878    3.2385    0.0418 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3 14  2  0
 14 15  1  0
 14 12  1  0
 12 13  1  0
 12 11  2  0
 11 10  1  0
 10  8  1  0
  8  9  2  0
  8  7  1  0
  7  6  2  0
  6  5  1  0
  5  4  2  0
  4  3  1  0
  5 11  1  0
  1 16  1  0
  1 17  1  0
  1 18  1  0
 15 23  1  0
 13 22  1  0
  7 21  1  0
  6 20  1  0
  4 19  1  0
M  END
Download

3D SDF for NP0051447 (Fraxetin)


  Mrv1652310051709242D          

 15 16  0  0  0  0            999 V2000
    5.0013   -0.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4289    0.0000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7145   -0.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8579    0.0000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1434   -0.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.5724   -0.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7145   -1.2375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.5724   -1.2375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8579   -1.6500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1434   -1.2375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000   -1.6500    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.2868   -1.6500    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.8579   -2.4750    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.2868   -0.0000    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.4289   -1.6500    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  3  2  2  0  0  0  0
  5  2  1  0  0  0  0
  5  4  2  0  0  0  0
  6  4  1  0  0  0  0
  7  3  1  0  0  0  0
  8  6  2  0  0  0  0
  9  8  1  0  0  0  0
 10  5  1  0  0  0  0
 10  9  2  0  0  0  0
 11  7  2  0  0  0  0
 12  8  1  0  0  0  0
 13  9  1  0  0  0  0
 14  1  1  0  0  0  0
 14  6  1  0  0  0  0
 15  7  1  0  0  0  0
 15 10  1  0  0  0  0
M  END
> <DATABASE_ID>
NP0051447

> <DATABASE_NAME>
NP-MRD

> <SMILES>
COC1=C(O)C(O)=C2OC(=O)C=CC2=C1

> <INCHI_IDENTIFIER>
InChI=1S/C10H8O5/c1-14-6-4-5-2-3-7(11)15-10(5)9(13)8(6)12/h2-4,12-13H,1H3

> <INCHI_KEY>
HAVWRBANWNTOJX-UHFFFAOYSA-N

> <FORMULA>
C10H8O5

> <MOLECULAR_WEIGHT>
208.169

> <EXACT_MASS>
208.037173358

> <JCHEM_ACCEPTOR_COUNT>
4

> <JCHEM_ATOM_COUNT>
23

> <JCHEM_AVERAGE_POLARIZABILITY>
19.174923500731595

> <JCHEM_BIOAVAILABILITY>
1

> <JCHEM_DONOR_COUNT>
2

> <JCHEM_FORMAL_CHARGE>
0

> <JCHEM_GHOSE_FILTER>
1

> <JCHEM_IUPAC>
7,8-dihydroxy-6-methoxy-2H-chromen-2-one

> <ALOGPS_LOGP>
1.74

> <JCHEM_LOGP>
1.668557706333333

> <ALOGPS_LOGS>
-1.85

> <JCHEM_MDDR_LIKE_RULE>
0

> <JCHEM_NUMBER_OF_RINGS>
2

> <JCHEM_PHYSIOLOGICAL_CHARGE>
0

> <JCHEM_PKA>
13.032745358957474

> <JCHEM_PKA_STRONGEST_ACIDIC>
8.620721178782452

> <JCHEM_PKA_STRONGEST_BASIC>
-4.445151001517632

> <JCHEM_POLAR_SURFACE_AREA>
75.99000000000001

> <JCHEM_REFRACTIVITY>
51.97360000000001

> <JCHEM_ROTATABLE_BOND_COUNT>
1

> <JCHEM_RULE_OF_FIVE>
1

> <ALOGPS_SOLUBILITY>
2.93e+00 g/l

> <JCHEM_TRADITIONAL_IUPAC>
fraxetin

> <JCHEM_VEBER_RULE>
0

$$$$
Download

3D-SDF for NP0051447 (Fraxetin)

Download
PDB for NP0051447 (Fraxetin)
HEADER    PROTEIN                                 05-OCT-17   NONE
TITLE     NULL                                                        
COMPND    NULL                                                        
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   05-OCT-17         0                                  
HETATM    1  C   UNK     0       9.336  -0.770   0.000  0.00  0.00           C+0
HETATM    2  C   UNK     0       2.667   0.000   0.000  0.00  0.00           C+0
HETATM    3  C   UNK     0       1.334  -0.770   0.000  0.00  0.00           C+0
HETATM    4  C   UNK     0       5.335   0.000   0.000  0.00  0.00           C+0
HETATM    5  C   UNK     0       4.001  -0.770   0.000  0.00  0.00           C+0
HETATM    6  C   UNK     0       6.668  -0.770   0.000  0.00  0.00           C+0
HETATM    7  C   UNK     0       1.334  -2.310   0.000  0.00  0.00           C+0
HETATM    8  C   UNK     0       6.668  -2.310   0.000  0.00  0.00           C+0
HETATM    9  C   UNK     0       5.335  -3.080   0.000  0.00  0.00           C+0
HETATM   10  C   UNK     0       4.001  -2.310   0.000  0.00  0.00           C+0
HETATM   11  O   UNK     0       0.000  -3.080   0.000  0.00  0.00           O+0
HETATM   12  O   UNK     0       8.002  -3.080   0.000  0.00  0.00           O+0
HETATM   13  O   UNK     0       5.335  -4.620   0.000  0.00  0.00           O+0
HETATM   14  O   UNK     0       8.002  -0.000   0.000  0.00  0.00           O+0
HETATM   15  O   UNK     0       2.667  -3.080   0.000  0.00  0.00           O+0
CONECT    1   14                                                            
CONECT    2    3    5                                                       
CONECT    3    2    7                                                       
CONECT    4    5    6                                                       
CONECT    5    2    4   10                                                  
CONECT    6    4    8   14                                                  
CONECT    7    3   11   15                                                  
CONECT    8    6    9   12                                                  
CONECT    9    8   10   13                                                  
CONECT   10    5    9   15                                                  
CONECT   11    7                                                            
CONECT   12    8                                                            
CONECT   13    9                                                            
CONECT   14    1    6                                                       
CONECT   15    7   10                                                       
MASTER        0    0    0    0    0    0    0    0   15    0   32    0
END

Download
3D PDB for NP0051447 (Fraxetin)
Download
SMILES for NP0051447 (Fraxetin)
COC1=C(O)C(O)=C2OC(=O)C=CC2=C1
Download
INCHI for NP0051447 (Fraxetin)
InChI=1S/C10H8O5/c1-14-6-4-5-2-3-7(11)15-10(5)9(13)8(6)12/h2-4,12-13H,1H3
Download
View in JSmol
Synonyms
ValueSource
7,8-Dihydroxy-6-methoxy-2-benzopyroneChEBI
7,8-Dihydroxy-6-methoxycoumarinChEBI
7,8-Dihydroxy-6-methoxy-2H-chromen-2-oneKegg
6-Methoxy-7,8-dihydroxycoumarinMeSH
Chemical FormulaC10H8O5
Average Mass208.1690 Da
Monoisotopic Mass208.03717 Da
IUPAC Name7,8-dihydroxy-6-methoxy-2H-chromen-2-one
Traditional Namefraxetin
CAS Registry NumberNot Available
SMILES
COC1=C(O)C(O)=C2OC(=O)C=CC2=C1
InChI Identifier
InChI=1S/C10H8O5/c1-14-6-4-5-2-3-7(11)15-10(5)9(13)8(6)12/h2-4,12-13H,1H3
InChI KeyHAVWRBANWNTOJX-UHFFFAOYSA-N
Experimental Spectra
Not Available
Predicted Spectra
Spectrum TypeDescriptionDepositor IDDepositor OrganizationDepositorDeposition DateView
1D NMR13C NMR Spectrum (1D, 25 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 252 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 50 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 75 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 101 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 126 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 151 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 176 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 201 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 226 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
Chemical Shift Submissions
Not Available
Species
Species of Origin
Species NameSourceReference
Acer nikoensePlant
Aesculus hippocastanumPlant
Aesculus turbinataPlant
Bupleurum fruticosumLOTUS Database
Campanula dolomiticaLOTUS Database
Echites hirsutaPlant
Fraxinus angustifoliaLOTUS Database
Fraxinus bungeanaPlant
Fraxinus chinensisPlant
Fraxinus floribundaPlant
Fraxinus japonica Seringe BlumePlant
Fraxinus mandshuricaLOTUS Database
Fraxinus ornusPlant
Fraxinus spp.Plant
Ginkgo bilobaPlant
Gochnatia argentinaPlant
Haplophyllum obtusifoliumLOTUS Database
Hydrangea vestitaPlant
Jatropha glanduliferaLOTUS Database
Ledum palustreLOTUS Database
Lupinus angustifoliusLOTUS Database
Mondia whiteiLOTUS Database
Ocotea odoriferaLOTUS Database
Pelargonium sidoidesPlant
Peltogyne confertifloraPlant
Protium heptaphyllumLOTUS Database
Pterocaulon purpurascensLOTUS Database
Salsola laricifoliaPlant
Santolina pinnataLOTUS Database
Sarcandra glabraLOTUS Database
Vestia lycioidesPlant
Chemical Taxonomy
Description Belongs to the class of organic compounds known as 7,8-dihydroxycoumarins. These are coumarins bearing two hydroxyl groups at the C7- and C8-positions of the coumarin skeleton, respectively.
KingdomOrganic compounds  
Super ClassPhenylpropanoids and polyketides  
ClassCoumarins and derivatives  
Sub ClassHydroxycoumarins  
Direct Parent7,8-dihydroxycoumarins  
Alternative Parents
Substituents
  • 7,8-dihydroxycoumarin
    • 

  • 7-hydroxycoumarin
    • 

  • Benzopyran
    • 

  • 1-benzopyran
    • 

  • Anisole
    • 

  • 1-hydroxy-4-unsubstituted benzenoid
    • 

  • Alkyl aryl ether
    • 

  • Pyranone
    • 

  • Pyran
    • 

  • Benzenoid
    • 

  • Heteroaromatic compound
    • 

  • Lactone
    • 

  • Organoheterocyclic compound
    • 

  • Ether
    • 

  • Oxacycle
    • 

  • Organooxygen compound
    • 

  • Hydrocarbon derivative
    • 

  • Organic oxygen compound
    • 

  • Organic oxide
    • 

  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Physical Properties
StateNot Available
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
logP1.74ALOGPS
logP1.67ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)8.62ChemAxon
pKa (Strongest Basic)-4.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area75.99 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity51.97 m³·mol⁻¹ChemAxon
Polarizability19.17 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
HMDB IDHMDB0149150  
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDC00002473  
Chemspider IDNot Available
KEGG Compound IDC09265  
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkFraxetin  
METLIN IDNot Available
PubChem Compound5273569  
PDB IDNot Available
ChEBI ID5169  
Good Scents IDNot Available
References
General References
  1. Fernandez-Puntero B, Barroso I, Iglesias I, Benedi J, Villar A: Antioxidant activity of Fraxetin: in vivo and ex vivo parameters in normal situation versus induced stress. Biol Pharm Bull. 2001 Jul;24(7):777-84. doi: 10.1248/bpb.24.777. [PubMed:11456117  ] 
  2. Molina-Jimenez MF, Sanchez-Reus MI, Benedi J: Effect of fraxetin and myricetin on rotenone-induced cytotoxicity in SH-SY5Y cells: comparison with N-acetylcysteine. Eur J Pharmacol. 2003 Jul 4;472(1-2):81-7. doi: 10.1016/s0014-2999(03)01902-2. [PubMed:12860476  ] 
  3. Molina-Jimenez MF, Sanchez-Reus MI, Andres D, Cascales M, Benedi J: Neuroprotective effect of fraxetin and myricetin against rotenone-induced apoptosis in neuroblastoma cells. Brain Res. 2004 May 29;1009(1-2):9-16. doi: 10.1016/j.brainres.2004.02.065. [PubMed:15120578  ] 
  4. Molina-Jimenez MF, Sanchez-Reus MI, Cascales M, Andres D, Benedi J: Effect of fraxetin on antioxidant defense and stress proteins in human neuroblastoma cell model of rotenone neurotoxicity. Comparative study with myricetin and N-acetylcysteine. Toxicol Appl Pharmacol. 2005 Dec 15;209(3):214-25. doi: 10.1016/j.taap.2005.04.009. [PubMed:15904944  ] 
  5. Sanchez-Reus MI, Peinado II, Molina-Jimenez MF, Benedi J: Fraxetin prevents rotenone-induced apoptosis by induction of endogenous glutathione in human neuroblastoma cells. Neurosci Res. 2005 Sep;53(1):48-56. doi: 10.1016/j.neures.2005.05.009. [PubMed:15996779  ]