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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2006-05-22 15:12:49 UTC
Update Date2019-07-23 05:45:44 UTC
HMDB IDHMDB0003306
Secondary Accession Numbers
  • HMDB03306
Metabolite Identification
Common NamePhloretin
DescriptionPhloretin is the aglucone of phlorizin, a plant-derived dihydrochalcone phytochemical reported to promote potent antioxidative activities in peroxynitrite scavenging and the inhibition of lipid peroxidation. Phloretin, which is present in apples, pears and tomatoes, has been found to inhibit the growth of several cancer cells and induce apoptosis of B16 melanoma and HL60 human leukemia cells. Phloretin also inhibits HT-29 cell growth by inducing apoptosis, which may be mediated through changes in mitochondrial membrane permeability and activation of the caspase pathways. Phloretin is a well-known inhibitor of eukaryotic urea transporters, blocks VacA-mediated urea and ion transport. (PMID: 18158826 , 11560962 , 18063724 , 15671209 , 12083758 ). Phloretin is a biomarker for the consumption of apples. Phloretin has been found to be a metabolite of Escherichia (PMID: 23542617 ).
Structure
Data?1563860744
Synonyms
ValueSource
3-(4-Hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)-1-propanoneChEBI
2,6-Dihydroxy-4-methoxyacetophenoneHMDB
4-O-MethylphloracetophenoneHMDB
DihydronaringeninHMDB
PhloretolHMDB
Chemical FormulaC15H14O5
Average Molecular Weight274.2687
Monoisotopic Molecular Weight274.084123558
IUPAC Name3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one
Traditional Namephloretin
CAS Registry Number60-82-2
SMILES
OC1=CC=C(CCC(=O)C2=C(O)C=C(O)C=C2O)C=C1
InChI Identifier
InChI=1S/C15H14O5/c16-10-4-1-9(2-5-10)3-6-12(18)15-13(19)7-11(17)8-14(15)20/h1-2,4-5,7-8,16-17,19-20H,3,6H2
InChI KeyVGEREEWJJVICBM-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as 2'-hydroxy-dihydrochalcones. These are organic compounds containing dihydrochalcone skeleton that carries a hydroxyl group at the 2'-position.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassLinear 1,3-diarylpropanoids
Sub ClassChalcones and dihydrochalcones
Direct Parent2'-Hydroxy-dihydrochalcones
Alternative Parents
Substituents
  • 2'-hydroxy-dihydrochalcone
  • Cinnamylphenol
  • Alkyl-phenylketone
  • Acylphloroglucinol derivative
  • Butyrophenone
  • Benzenetriol
  • Phloroglucinol derivative
  • Phenylketone
  • Aryl alkyl ketone
  • Aryl ketone
  • Benzoyl
  • Phenol
  • 1-hydroxy-2-unsubstituted benzenoid
  • 1-hydroxy-4-unsubstituted benzenoid
  • Benzenoid
  • Monocyclic benzene moiety
  • Vinylogous acid
  • Ketone
  • Polyol
  • Organic oxide
  • Organic oxygen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Source:

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point263.5 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.12 mg/mL at 16 °CNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.13 g/LALOGPS
logP2.23ALOGPS
logP3.9ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)7.96ChemAxon
pKa (Strongest Basic)-4.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area97.99 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity73.71 m³·mol⁻¹ChemAxon
Polarizability27.75 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-002f-0915000000-2cd118505cf4ff16b664JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-002f-0915000000-2cd118505cf4ff16b664JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0udi-2920000000-ce9a5fce0e77c981b6d3JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (4 TMS) - 70eV, Positivesplash10-00r2-2207490000-670b5b16c28fb6b692e3JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0006-1900000000-b990d3eca878be81222bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-014i-2900000000-4eb9bf83b7d70a97bd0bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0w2c-4900000000-77d3779ddd5455f0b9a3JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITTOF (LCMS-IT-TOF) , Positivesplash10-004i-0090000000-a2a168a2f04c479df8edJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITTOF (LCMS-IT-TOF) , Negativesplash10-00dj-0090050000-15d417468db5c396463eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITTOF (LCMS-IT-TOF) , Positivesplash10-0a4i-0900000000-bc6e2e1009d1b50ad9f7JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-00xr-0690000000-e5774d71d08a1df83336JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0900000000-d051b74295a78047c5f0JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-01b9-0900000000-6e6539df4cbbef8d26b3JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-01b9-0940000000-e06c676ae64bfbb5107bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-014i-0900000000-949e95a0767d512e3d04JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-014i-0910000000-bb2134d05e29fff0bc78JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-014i-0910000000-eb3ed13a8222a6f19622JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0290000000-826fa92be2be280f2e5eJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0zfr-0930000000-6abeede53ef1753e2613JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-2900000000-a2ba5d714e72373837bbJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0290000000-8a18e7ae5b70f7a0683fJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00b9-0930000000-66ecbda03ca96ea053b3JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-3910000000-831048d96d049d47cd92JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0290000000-826fa92be2be280f2e5eJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0zfr-0930000000-6abeede53ef1753e2613JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-2900000000-a2ba5d714e72373837bbJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0290000000-8a18e7ae5b70f7a0683fJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00b9-0930000000-66ecbda03ca96ea053b3JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-3910000000-831048d96d049d47cd92JSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biospecimen Locations
  • Blood
  • Urine
Tissue Locations
  • Fibroblasts
  • Intestine
  • Platelet
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot Available
Normal
    details
    UrineDetected and Quantified0.0152 umol/mmol creatinineAdult (>18 years old)BothNormal details
    UrineDetected and Quantified0.0420 +/- 0.0500 umol/mmol creatinineAdult (>18 years old)BothNormal details
    UrineDetected and Quantified0.0487 +/- 0.127 umol/mmol creatinineAdult (>18 years old)BothNormal details
    UrineExpected but not Quantified Not AvailableNot AvailableConsuming polyphenols described by Phenol-Explorer entry 108 details
    UrineDetected and Quantified50 umol/mmol creatinineAdult (>18 years old)Both
    Normal
    details
    UrineDetected and Quantified40 umol/mmol creatinineAdult (>18 years old)Both
    Normal
    details
    UrineDetected and Quantified0.098 +/- 0.10 umol/mmol creatinineAdult (>18 years old)BothNormal details
    UrineDetected and Quantified0.046 +/- 0.026 umol/mmol creatinineAdult (>18 years old)BothNormal details
    UrineDetected and Quantified0.0247 umol/mmol creatinineAdult (>18 years old)Both
    Normal
    details
    UrineDetected and Quantified0.0525 +/- 0.0510 umol/mmol creatinineAdult (>18 years old)Both
    Normal
    details
    Abnormal Concentrations
    Not Available
    Associated Disorders and Diseases
    Disease ReferencesNone
    Associated OMIM IDsNone
    DrugBank IDDB07810
    Phenol Explorer Compound ID108
    FoodDB IDFDB015553
    KNApSAcK IDC00007936
    Chemspider ID4624
    KEGG Compound IDC00774
    BioCyc IDPHLORETIN
    BiGG IDNot Available
    Wikipedia LinkPhloretin
    METLIN ID3405
    PubChem Compound4788
    PDB IDNot Available
    ChEBI ID17276
    Food Biomarker OntologyNot Available
    VMH IDNot Available
    References
    Synthesis ReferenceNot Available
    Material Safety Data Sheet (MSDS)Download (PDF)
    General References
    1. Sharif NA, Crider JY, Davis TL: AL-3138 antagonizes FP prostanoid receptor-mediated inositol phosphates generation: comparison with some purported FP antagonists. J Pharm Pharmacol. 2000 Dec;52(12):1529-39. [PubMed:11197083 ]
    2. Fan HT, Morishima S, Kida H, Okada Y: Phloretin differentially inhibits volume-sensitive and cyclic AMP-activated, but not Ca-activated, Cl(-) channels. Br J Pharmacol. 2001 Aug;133(7):1096-106. [PubMed:11487521 ]
    3. Stangl V, Lorenz M, Ludwig A, Grimbo N, Guether C, Sanad W, Ziemer S, Martus P, Baumann G, Stangl K: The flavonoid phloretin suppresses stimulated expression of endothelial adhesion molecules and reduces activation of human platelets. J Nutr. 2005 Feb;135(2):172-8. [PubMed:15671209 ]
    4. Rasmussen SE, Breinholt VM: Non-nutritive bioactive food constituents of plants: bioavailability of flavonoids. Int J Vitam Nutr Res. 2003 Mar;73(2):101-11. [PubMed:12747217 ]
    5. Nielsen SE, Freese R, Kleemola P, Mutanen M: Flavonoids in human urine as biomarkers for intake of fruits and vegetables. Cancer Epidemiol Biomarkers Prev. 2002 May;11(5):459-66. [PubMed:12010860 ]
    6. DuPont MS, Bennett RN, Mellon FA, Williamson G: Polyphenols from alcoholic apple cider are absorbed, metabolized and excreted by humans. J Nutr. 2002 Feb;132(2):172-5. [PubMed:11823574 ]
    7. Ito H, Gonthier MP, Manach C, Morand C, Mennen L, Remesy C, Scalbert A: Polyphenol levels in human urine after intake of six different polyphenol-rich beverages. Br J Nutr. 2005 Oct;94(4):500-9. [PubMed:16197573 ]
    8. Zerbini G, Podesta F, Meregalli G, Deferrari G, Pontremoli R: Fibroblast Na+-Li+ countertransport rate is elevated in essential hypertension. J Hypertens. 2001 Jul;19(7):1263-9. [PubMed:11446716 ]
    9. Park SY, Kim EJ, Shin HK, Kwon DY, Kim MS, Surh YJ, Park JH: Induction of apoptosis in HT-29 colon cancer cells by phloretin. J Med Food. 2007 Dec;10(4):581-6. [PubMed:18158826 ]
    10. Tombola F, Morbiato L, Del Giudice G, Rappuoli R, Zoratti M, Papini E: The Helicobacter pylori VacA toxin is a urea permease that promotes urea diffusion across epithelia. J Clin Invest. 2001 Sep;108(6):929-37. [PubMed:11560962 ]
    11. Pajor AM, Randolph KM, Kerner SA, Smith CD: Inhibitor binding in the human renal low- and high-affinity Na+/glucose cotransporters. J Pharmacol Exp Ther. 2008 Mar;324(3):985-91. Epub 2007 Dec 6. [PubMed:18063724 ]
    12. Rezk BM, Haenen GR, van der Vijgh WJ, Bast A: The antioxidant activity of phloretin: the disclosure of a new antioxidant pharmacophore in flavonoids. Biochem Biophys Res Commun. 2002 Jul 5;295(1):9-13. [PubMed:12083758 ]
    13. Pandey RP, Li TF, Kim EH, Yamaguchi T, Park YI, Kim JS, Sohng JK: Enzymatic synthesis of novel phloretin glucosides. Appl Environ Microbiol. 2013 Jun;79(11):3516-21. doi: 10.1128/AEM.00409-13. Epub 2013 Mar 29. [PubMed:23542617 ]

    Enzymes

    General function:
    Involved in transferase activity, transferring hexosyl groups
    Specific function:
    UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone.
    Gene Name:
    UGT1A1
    Uniprot ID:
    P22309
    Molecular weight:
    59590.91
    Reactions
    Phloretin → 3,4,5-trihydroxy-6-{4-[3-oxo-3-(2,4,6-trihydroxyphenyl)propyl]phenoxy}oxane-2-carboxylic aciddetails
    Phloretin → 6-{3,5-dihydroxy-2-[3-(4-hydroxyphenyl)propanoyl]phenoxy}-3,4,5-trihydroxyoxane-2-carboxylic aciddetails
    Phloretin → 6-{3,5-dihydroxy-4-[3-(4-hydroxyphenyl)propanoyl]phenoxy}-3,4,5-trihydroxyoxane-2-carboxylic aciddetails
    General function:
    sulfotransferase activity
    Specific function:
    Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of phenolic monoamines (neurotransmitters such as dopamine, norepinephrine and serotonin) and phenolic and catechol drugs.
    Gene Name:
    SULT1A3
    Uniprot ID:
    P0DMM9
    Molecular weight:
    34195.96
    Reactions
    Phloretin → Dihydronaringenin-O-sulphatedetails