Hmdb loader

Showing metabocard for Quinaldic acid (HMDB0000842)

Jump To Section:
IdentificationTaxonomyOntologyPhysical propertiesSpectraBiological propertiesConcentrationsLinksReferencesXML
Show more...Show more...Show more...
Record Information
Version5.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2023-05-30 20:55:48 UTC
HMDB IDHMDB0000842
Secondary Accession Numbers
  • HMDB00842
Metabolite Identification
Common NameQuinaldic acid
DescriptionQuinaldic acid, also known as quinaldate, 2-carboxyquinoline, or quinoline-2-carboxylic acid, belongs to the class of organic compounds known as quinoline carboxylic acids. These are quinolines in which the quinoline ring system is substituted by a carboxyl group at one or more positions. The quinoline ring system is a double-ring structure composed of a benzene and a pyridine ring fused at two adjacent carbon atoms. Quinaldic acid is a quinoline having a carboxy group at the 2-position. It is a solid that is moderately soluble in water with a melting point of 156°C. Quinaldic acid is a metabolite of tryptophan degradation that is formed via the kynurenine pathway; it is formed through the dehydroxylation of the intermediate kynurenic acid (PMID: 13385219 ). It is excreted in urine, and its urine concentration is decreased in individuals suffering from chronic alcoholism (PMID: 25754126 ). Quinaldic acid has been shown to inhibit proinsulin synthesis in pancreatic islet cells (PMID: 373355 ). Quinaldic acid has been shown to have anti-proliferative or anti-tumour effects and has been found to alter the expression of the p53 tumour suppressor gene as well as the phosphorylation of the p53 protein in in vitro studies (PMID: 30780127 ).
Structure
Data?1676999713
MOL3D MOLSDF3D SDFPDB3D PDBSMILESInChI

MOL for HMDB0000842 (Quinaldic acid)

QND
  Mrv1652305271900282D          

 13 14  0  0  0  0            999 V2000
   -0.3867   -0.7913    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1012   -0.3788    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1012    0.4462    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3867    0.8587    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0422    0.8587    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7567    0.4462    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7567   -0.3788    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0422   -0.7913    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3277    0.4462    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3277   -0.3788    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8157   -0.7913    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8157   -1.6163    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5301   -0.3788    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0  0  0  0
  1 10  1  0  0  0  0
  2  3  1  0  0  0  0
  2 11  1  0  0  0  0
  3  4  2  0  0  0  0
  4  9  1  0  0  0  0
  5  6  2  0  0  0  0
  5  9  1  0  0  0  0
  6  7  1  0  0  0  0
  7  8  2  0  0  0  0
  8 10  1  0  0  0  0
  9 10  2  0  0  0  0
 11 12  2  0  0  0  0
 11 13  1  0  0  0  0
M  END
Download

3D MOL for HMDB0000842 (Quinaldic acid)

HMDB0000842
     RDKit          3D
Quinaldic acid
 20 21  0  0  0  0  0  0  0  0999 V2000
    4.0060   -1.0174    0.9887 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.0131   -0.3876    1.4334 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0799    0.3066    2.6318 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.7519   -0.3649    0.7020 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6503   -1.0455   -0.4949 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.4521   -1.0357   -1.2093 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6225   -0.3325   -0.6918 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8349   -0.2723   -1.3308 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9253    0.4207   -0.8401 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7473    1.0764    0.3620 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5545    1.0516    1.0480 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4918    0.3424    0.5133 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6832    0.2949    1.1507 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.5009    1.2460    2.5673 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.4958   -1.5863   -0.8812 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.3321   -1.5504   -2.1408 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9413   -0.7973   -2.2714 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8798    0.4658   -1.3471 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5684    1.6275    0.7803 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3995    1.5580    1.9871 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  2  4  1  0
  4  5  2  0
  5  6  1  0
  6  7  2  0
  7  8  1  0
  8  9  2  0
  9 10  1  0
 10 11  2  0
 11 12  1  0
 12 13  2  0
 13  4  1  0
 12  7  1  0
  3 14  1  0
  5 15  1  0
  6 16  1  0
  8 17  1  0
  9 18  1  0
 10 19  1  0
 11 20  1  0
M  END
Download

3D SDF for HMDB0000842 (Quinaldic acid)

QND
  Mrv1652305271900282D          

 13 14  0  0  0  0            999 V2000
   -0.3867   -0.7913    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1012   -0.3788    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1012    0.4462    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3867    0.8587    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0422    0.8587    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7567    0.4462    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7567   -0.3788    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0422   -0.7913    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3277    0.4462    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3277   -0.3788    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8157   -0.7913    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8157   -1.6163    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5301   -0.3788    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0  0  0  0
  1 10  1  0  0  0  0
  2  3  1  0  0  0  0
  2 11  1  0  0  0  0
  3  4  2  0  0  0  0
  4  9  1  0  0  0  0
  5  6  2  0  0  0  0
  5  9  1  0  0  0  0
  6  7  1  0  0  0  0
  7  8  2  0  0  0  0
  8 10  1  0  0  0  0
  9 10  2  0  0  0  0
 11 12  2  0  0  0  0
 11 13  1  0  0  0  0
M  END
> <DATABASE_ID>
HMDB0000842

> <DATABASE_NAME>
hmdb

> <SMILES>
OC(=O)C1=NC2=C(C=CC=C2)C=C1

> <INCHI_IDENTIFIER>
InChI=1S/C10H7NO2/c12-10(13)9-6-5-7-3-1-2-4-8(7)11-9/h1-6H,(H,12,13)

> <INCHI_KEY>
LOAUVZALPPNFOQ-UHFFFAOYSA-N

> <FORMULA>
C10H7NO2

> <MOLECULAR_WEIGHT>
173.1681

> <EXACT_MASS>
173.047678473

> <JCHEM_ACCEPTOR_COUNT>
3

> <JCHEM_ATOM_COUNT>
20

> <JCHEM_AVERAGE_POLARIZABILITY>
17.26843664448372

> <JCHEM_BIOAVAILABILITY>
1

> <JCHEM_DONOR_COUNT>
1

> <JCHEM_FORMAL_CHARGE>
0

> <JCHEM_GHOSE_FILTER>
1

> <JCHEM_IUPAC>
quinoline-2-carboxylic acid

> <ALOGPS_LOGP>
1.44

> <JCHEM_LOGP>
0.7862466196645604

> <ALOGPS_LOGS>
-2.36

> <JCHEM_MDDR_LIKE_RULE>
0

> <JCHEM_NUMBER_OF_RINGS>
2

> <JCHEM_PHYSIOLOGICAL_CHARGE>
-1

> <JCHEM_PKA_STRONGEST_ACIDIC>
1.0967744376974862

> <JCHEM_PKA_STRONGEST_BASIC>
5.22267490435857

> <JCHEM_POLAR_SURFACE_AREA>
50.19

> <JCHEM_REFRACTIVITY>
46.8635

> <JCHEM_ROTATABLE_BOND_COUNT>
1

> <JCHEM_RULE_OF_FIVE>
1

> <ALOGPS_SOLUBILITY>
7.60e-01 g/l

> <JCHEM_TRADITIONAL_IUPAC>
quinaldic acid

> <JCHEM_VEBER_RULE>
0

$$$$
Download

3D-SDF for HMDB0000842 (Quinaldic acid)

HMDB0000842
     RDKit          3D
Quinaldic acid
 20 21  0  0  0  0  0  0  0  0999 V2000
    4.0060   -1.0174    0.9887 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.0131   -0.3876    1.4334 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0799    0.3066    2.6318 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.7519   -0.3649    0.7020 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6503   -1.0455   -0.4949 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.4521   -1.0357   -1.2093 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6225   -0.3325   -0.6918 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8349   -0.2723   -1.3308 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9253    0.4207   -0.8401 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7473    1.0764    0.3620 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5545    1.0516    1.0480 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4918    0.3424    0.5133 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6832    0.2949    1.1507 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.5009    1.2460    2.5673 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.4958   -1.5863   -0.8812 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.3321   -1.5504   -2.1408 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9413   -0.7973   -2.2714 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8798    0.4658   -1.3471 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5684    1.6275    0.7803 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3995    1.5580    1.9871 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  2  4  1  0
  4  5  2  0
  5  6  1  0
  6  7  2  0
  7  8  1  0
  8  9  2  0
  9 10  1  0
 10 11  2  0
 11 12  1  0
 12 13  2  0
 13  4  1  0
 12  7  1  0
  3 14  1  0
  5 15  1  0
  6 16  1  0
  8 17  1  0
  9 18  1  0
 10 19  1  0
 11 20  1  0
M  END
Download

PDB for HMDB0000842 (Quinaldic acid)

HEADER    PROTEIN                                 27-MAY-19   NONE
TITLE     NULL                                                        
COMPND    MOLECULE: QND                                               
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   27-MAY-19         0                                  
HETATM    1  N   UNK     0      -0.722  -1.477   0.000  0.00  0.00           N+0
HETATM    2  C   UNK     0      -2.056  -0.707   0.000  0.00  0.00           C+0
HETATM    3  C   UNK     0      -2.056   0.833   0.000  0.00  0.00           C+0
HETATM    4  C   UNK     0      -0.722   1.603   0.000  0.00  0.00           C+0
HETATM    5  C   UNK     0       1.945   1.603   0.000  0.00  0.00           C+0
HETATM    6  C   UNK     0       3.279   0.833   0.000  0.00  0.00           C+0
HETATM    7  C   UNK     0       3.279  -0.707   0.000  0.00  0.00           C+0
HETATM    8  C   UNK     0       1.945  -1.477   0.000  0.00  0.00           C+0
HETATM    9  C   UNK     0       0.612   0.833   0.000  0.00  0.00           C+0
HETATM   10  C   UNK     0       0.612  -0.707   0.000  0.00  0.00           C+0
HETATM   11  C   UNK     0      -3.389  -1.477   0.000  0.00  0.00           C+0
HETATM   12  O   UNK     0      -3.389  -3.017   0.000  0.00  0.00           O+0
HETATM   13  O   UNK     0      -4.723  -0.707   0.000  0.00  0.00           O+0
CONECT    1    2   10                                                       
CONECT    2    1    3   11                                                  
CONECT    3    2    4                                                       
CONECT    4    3    9                                                       
CONECT    5    6    9                                                       
CONECT    6    5    7                                                       
CONECT    7    6    8                                                       
CONECT    8    7   10                                                       
CONECT    9    4    5   10                                                  
CONECT   10    1    8    9                                                  
CONECT   11    2   12   13                                                  
CONECT   12   11                                                            
CONECT   13   11                                                            
MASTER        0    0    0    0    0    0    0    0   13    0   28    0
END
Download

3D PDB for HMDB0000842 (Quinaldic acid)

COMPND    HMDB0000842
HETATM    1  O1  UNL     1       4.006  -1.017   0.989  1.00  0.00           O  
HETATM    2  C1  UNL     1       3.013  -0.388   1.433  1.00  0.00           C  
HETATM    3  O2  UNL     1       3.080   0.307   2.632  1.00  0.00           O  
HETATM    4  C2  UNL     1       1.752  -0.365   0.702  1.00  0.00           C  
HETATM    5  C3  UNL     1       1.650  -1.045  -0.495  1.00  0.00           C  
HETATM    6  C4  UNL     1       0.452  -1.036  -1.209  1.00  0.00           C  
HETATM    7  C5  UNL     1      -0.622  -0.332  -0.692  1.00  0.00           C  
HETATM    8  C6  UNL     1      -1.835  -0.272  -1.331  1.00  0.00           C  
HETATM    9  C7  UNL     1      -2.925   0.421  -0.840  1.00  0.00           C  
HETATM   10  C8  UNL     1      -2.747   1.076   0.362  1.00  0.00           C  
HETATM   11  C9  UNL     1      -1.554   1.052   1.048  1.00  0.00           C  
HETATM   12  C10 UNL     1      -0.492   0.342   0.513  1.00  0.00           C  
HETATM   13  N1  UNL     1       0.683   0.295   1.151  1.00  0.00           N  
HETATM   14  H1  UNL     1       3.501   1.246   2.567  1.00  0.00           H  
HETATM   15  H2  UNL     1       2.496  -1.586  -0.881  1.00  0.00           H  
HETATM   16  H3  UNL     1       0.332  -1.550  -2.141  1.00  0.00           H  
HETATM   17  H4  UNL     1      -1.941  -0.797  -2.271  1.00  0.00           H  
HETATM   18  H5  UNL     1      -3.880   0.466  -1.347  1.00  0.00           H  
HETATM   19  H6  UNL     1      -3.568   1.627   0.780  1.00  0.00           H  
HETATM   20  H7  UNL     1      -1.400   1.558   1.987  1.00  0.00           H  
CONECT    1    2    2
CONECT    2    3    4
CONECT    3   14
CONECT    4    5    5   13
CONECT    5    6   15
CONECT    6    7    7   16
CONECT    7    8   12
CONECT    8    9    9   17
CONECT    9   10   18
CONECT   10   11   11   19
CONECT   11   12   20
CONECT   12   13   13
END
Download

SMILES for HMDB0000842 (Quinaldic acid)

OC(=O)C1=NC2=C(C=CC=C2)C=C1
Download

INCHI for HMDB0000842 (Quinaldic acid)

InChI=1S/C10H7NO2/c12-10(13)9-6-5-7-3-1-2-4-8(7)11-9/h1-6H,(H,12,13)
Download
View in JSmolView Stereo Labels
Synonyms
ValueSource
2-CarboxyquinolineChEBI
2-ChinolincarbonsaeureChEBI
2-QuinolinecarboxylateChEBI
2-Quinolinecarboxylic acidChEBI
ChinaldinsaeureChEBI
QuinaldateChEBI
Quinaldinic acidChEBI
Quinoline-2-carboxylic acidChEBI
QuinaldinateGenerator
Quinoline-2-carboxylateGenerator
2-QuinolinylcarboxylateHMDB
2-Quinolinylcarboxylic acidHMDB
Quinolin-2-carboxylateHMDB
Quinolin-2-carboxylic acidHMDB
Quinaldic acidKEGG
Chemical FormulaC10H7NO2
Average Molecular Weight173.1681
Monoisotopic Molecular Weight173.047678473
IUPAC Namequinoline-2-carboxylic acid
Traditional Namequinaldic acid
CAS Registry Number93-10-7
SMILES
OC(=O)C1=NC2=C(C=CC=C2)C=C1
InChI Identifier
InChI=1S/C10H7NO2/c12-10(13)9-6-5-7-3-1-2-4-8(7)11-9/h1-6H,(H,12,13)
InChI KeyLOAUVZALPPNFOQ-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as quinoline carboxylic acids. These are quinolines in which the quinoline ring system is substituted by a carboxyl group at one or more positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassQuinoline carboxylic acids
Direct ParentQuinoline carboxylic acids
Alternative Parents
Substituents
  • Quinoline-2-carboxylic acid
  • Pyridine carboxylic acid
  • Pyridine carboxylic acid or derivatives
  • Benzenoid
  • Pyridine
  • Heteroaromatic compound
  • Carboxylic acid derivative
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Azacycle
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effect
Health effect
Disposition
Source
ProcessNot Available
Role
Industrial applicationBiological role
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point156 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility14 mg/mLNot Available
LogPNot AvailableNot Available
Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct TypeData SourceCCS Value (Å2)Reference
[M+H]+Not Available132.6http://allccs.zhulab.cn/database/detail?ID=AllCCS00002168
Predicted Molecular Properties
Predicted Chromatographic Properties
Spectra
Biological Properties
Cellular LocationsNot Available
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
UrineDetected and Quantified0.01 (0.01-0.02) umol/mmol creatinineNewborn (0-30 days old)Both
Normal
    • Analysis of 40 NI...
 details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot SpecifiedNot SpecifiedCancer patients undergoing total body irradiation details
UrineDetected but not QuantifiedNot QuantifiedNot SpecifiedNot SpecifiedCancer patients undergoing total body irradiation details
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB02428
Phenol Explorer Compound IDNot Available
FooDB IDFDB022275
KNApSAcK IDC00056094
Chemspider ID6857
KEGG Compound IDC06325
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN ID5805
PubChem Compound7124
PDB IDNot Available
ChEBI ID18386
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDrw1050261
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Epand RM: The role of dietary ergothioneine in the development of diabetes mellitus. Med Hypotheses. 1982 Aug;9(2):207-13. [PubMed:7144630 ]
  2. Okamoto H, Miyamoto S, Mabuchi H, Takeda R: Inhibition effect of quinaldic acid on glucose-induced insulin release from isolated Langerhans islets of the rat. Biochem Biophys Res Commun. 1974 Jul 24;59(2):623-9. [PubMed:4368820 ]
  3. Ektova LV, Iartseva IV, Khorosheva EV, Ivanova TP, Iavorskaia NP, Mel'nik SIa: [Synthesis and biological properties of pyrimidine 2'-deoxynucleosides modified by a residue of quinaldic acid]. Bioorg Khim. 1995 Aug;21(8):625-31. [PubMed:8540903 ]
  4. KAIHARA M, PRICE JM, TAKAHASHI H: The conversion of kynurenic acid to quinaldic acid by humans and rats. J Biol Chem. 1956 Dec;223(2):705-8. [PubMed:13385219 ]
  5. Mittal A, Dabur R: Detection of new human metabolic urinary markers in chronic alcoholism and their reversal by aqueous extract of Tinospora cordifolia stem. Alcohol Alcohol. 2015 May;50(3):271-81. doi: 10.1093/alcalc/agv012. Epub 2015 Mar 8. [PubMed:25754126 ]
  6. Noto Y, Okamoto H: Inhibition by kynurenine metabolites of proinsulin synthesis in isolated pancreatic islets. Acta Diabetol Lat. 1978 Sep-Dec;15(5-6):273-82. doi: 10.1007/BF02590750. [PubMed:373355 ]
  7. Langner E, Jeleniewicz W, Turski WA, Plech T: Quinaldic acid induces changes in the expression of p53 tumor suppressor both on protein and gene level in colon cancer LS180 cells. Pharmacol Rep. 2019 Apr;71(2):189-193. doi: 10.1016/j.pharep.2018.10.016. Epub 2018 Oct 30. [PubMed:30780127 ]