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Identification
NameHesperetin
Accession NumberDB01094  (APRD00117)
TypeSmall Molecule
GroupsApproved
DescriptionHesperetin belongs to the flavanone class of flavonoids. Hesperetin, in the form of its glycoside hesperidin, is the predominant flavonoid in lemons and oranges.
Structure
Thumb
Synonyms
(-)-(S)-Hesperetin
(-)-Hesperetin
(S)-2,3-dihydro-5,7-Dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-1-benzopyran-4-one
3',5,7-Trihydroxy-4'-methoxyflavanone
Cyanidanon 4'-Methyl Ether 1626
Hesperetin
Hesperitin
YSO2
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
HesperinNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIQ9Q3D557F1
CAS number520-33-2
WeightAverage: 302.2788
Monoisotopic: 302.07903818
Chemical FormulaC16H14O6
InChI KeyInChIKey=AIONOLUJZLIMTK-AWEZNQCLSA-N
InChI
InChI=1S/C16H14O6/c1-21-13-3-2-8(4-10(13)18)14-7-12(20)16-11(19)5-9(17)6-15(16)22-14/h2-6,14,17-19H,7H2,1H3/t14-/m0/s1
IUPAC Name
(2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-3,4-dihydro-2H-1-benzopyran-4-one
SMILES
COC1=C(O)C=C(C=C1)[C@@H]1CC(=O)C2=C(O)C=C(O)C=C2O1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 4'-o-methylated flavonoids. These are flavonoids with methoxy groups attached to the C4' atom of the flavonoid backbone.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassFlavonoids
Sub ClassO-methylated flavonoids
Direct Parent4'-O-methylated flavonoids
Alternative Parents
Substituents
  • 4p-methoxyflavonoid-skeleton
  • Hydroxyflavonoid
  • Flavanone
  • 7-hydroxyflavonoid
  • 5-hydroxyflavonoid
  • 3'-hydroxyflavonoid
  • Flavan
  • Chromone
  • 1-benzopyran
  • Methoxyphenol
  • Benzopyran
  • Chromane
  • Methoxybenzene
  • Aryl alkyl ketone
  • Aryl ketone
  • Resorcinol
  • Phenol ether
  • Anisole
  • Phenol
  • Alkyl aryl ether
  • Benzenoid
  • Monocyclic benzene moiety
  • Vinylogous acid
  • Ketone
  • Oxacycle
  • Organoheterocyclic compound
  • Ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor lowering cholesterol and, possibly, otherwise favorably affecting lipids. In vitro research also suggests the possibility that hesperetin might have some anticancer effects and that it might have some anti-aromatase activity, as well as activity again.
PharmacodynamicsHesperetin is a cholesterol lowering flavanoid found in a number of citrus juices. It appears to reduce cholesteryl ester mass and inhibit apoB secretion by up to 80%. Hesperetin may have antioxidant, anti-inflammatory, anti-allergic, hypolipidemic, vasoprotective and anticarcinogenic actions.
Mechanism of actionHesperetin reduces or inhibits the activity of acyl-coenzyme A:cholesterol acyltransferase genes (ACAT1 and ACAT2) and it reduces microsomal triglyceride transfer protein (MTP) activity. Hesperetin also seems to upregulate the LDL receptor. This leads to the reduced assembly and secretion of apoB-containing lipoproteins and enhanced reuptake of those lipoproteins, thereby lowering cholesterol levels.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
SubstrateEnzymesProduct
Hesperetin
eriodictyolDetails
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
PropertyValueProbability
Human Intestinal Absorption+0.9511
Blood Brain Barrier-0.6591
Caco-2 permeable+0.8286
P-glycoprotein substrateSubstrate0.6682
P-glycoprotein inhibitor INon-inhibitor0.743
P-glycoprotein inhibitor IIInhibitor0.5576
Renal organic cation transporterNon-inhibitor0.8866
CYP450 2C9 substrateNon-substrate0.7059
CYP450 2D6 substrateNon-substrate0.863
CYP450 3A4 substrateNon-substrate0.5067
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorInhibitor0.8949
CYP450 2D6 inhibitorInhibitor0.651
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorInhibitor0.7959
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7998
Ames testNon AMES toxic0.8777
CarcinogenicityNon-carcinogens0.9483
BiodegradationNot ready biodegradable0.8978
Rat acute toxicity3.1455 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9747
hERG inhibition (predictor II)Non-inhibitor0.8574
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point227.5 °CPhysProp
water solubility273 mg/LNot Available
logP2.60PERRISSOUD,D & TESTA,B (1986)
Predicted Properties
PropertyValueSource
Water Solubility0.138 mg/mLALOGPS
logP2.52ALOGPS
logP2.68ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)7.92ChemAxon
pKa (Strongest Basic)-3.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area96.22 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity77.75 m3·mol-1ChemAxon
Polarizability29.3 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Hesperetin can be increased when it is combined with Abiraterone.
AzithromycinThe metabolism of Hesperetin can be decreased when combined with Azithromycin.
BortezomibThe metabolism of Hesperetin can be decreased when combined with Bortezomib.
CaffeineThe metabolism of Hesperetin can be decreased when combined with Caffeine.
CarbamazepineThe metabolism of Hesperetin can be increased when combined with Carbamazepine.
CitalopramThe metabolism of Hesperetin can be decreased when combined with Citalopram.
ClotrimazoleThe metabolism of Hesperetin can be decreased when combined with Clotrimazole.
Cyproterone acetateThe serum concentration of Hesperetin can be decreased when it is combined with Cyproterone acetate.
DeferasiroxThe serum concentration of Hesperetin can be increased when it is combined with Deferasirox.
FluvoxamineThe metabolism of Hesperetin can be decreased when combined with Fluvoxamine.
LidocaineThe metabolism of Hesperetin can be decreased when combined with Lidocaine.
MexiletineThe metabolism of Hesperetin can be decreased when combined with Mexiletine.
NevirapineThe metabolism of Hesperetin can be decreased when combined with Nevirapine.
OsimertinibThe serum concentration of Hesperetin can be decreased when it is combined with Osimertinib.
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Hesperetin.
Peginterferon alfa-2bThe serum concentration of Hesperetin can be increased when it is combined with Peginterferon alfa-2b.
PhenobarbitalThe metabolism of Hesperetin can be increased when combined with Phenobarbital.
PrimidoneThe metabolism of Hesperetin can be increased when combined with Primidone.
RifampicinThe metabolism of Hesperetin can be increased when combined with Rifampicin.
RopiniroleThe metabolism of Hesperetin can be decreased when combined with Ropinirole.
SimeprevirThe metabolism of Hesperetin can be decreased when combined with Simeprevir.
TenofovirThe metabolism of Hesperetin can be decreased when combined with Tenofovir.
TeriflunomideThe serum concentration of Hesperetin can be decreased when it is combined with Teriflunomide.
TheophyllineThe metabolism of Hesperetin can be decreased when combined with Theophylline.
TiclopidineThe metabolism of Hesperetin can be decreased when combined with Ticlopidine.
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Hesperetin.
VemurafenibThe serum concentration of Hesperetin can be increased when it is combined with Vemurafenib.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Protein heterodimerization activity
Specific Function:
Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces (PubMed:23475612, PubMed:8939939, PubMed:26224785, PubMed:25108285, PubMed:22236406). Required for the secretion of plasma lipoproteins that contain apolipoprotein B (PubMed:23475612, PubMed:8939939, PubMed:26224785).
Gene Name:
MTTP
Uniprot ID:
P55157
Molecular Weight:
99350.255 Da
References
  1. Wilcox LJ, Borradaile NM, de Dreu LE, Huff MW: Secretion of hepatocyte apoB is inhibited by the flavonoids, naringenin and hesperetin, via reduced activity and expression of ACAT2 and MTP. J Lipid Res. 2001 May;42(5):725-34. [PubMed:11352979 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Sterol o-acyltransferase activity
Specific Function:
Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol. Plays a role in lipoprotein assembly and dietary cholesterol absorption. In addition to its acyltransferase activity, it may act as a ligase.
Gene Name:
SOAT1
Uniprot ID:
P35610
Molecular Weight:
64733.975 Da
References
  1. Wilcox LJ, Borradaile NM, de Dreu LE, Huff MW: Secretion of hepatocyte apoB is inhibited by the flavonoids, naringenin and hesperetin, via reduced activity and expression of ACAT2 and MTP. J Lipid Res. 2001 May;42(5):725-34. [PubMed:11352979 ]
  2. Chung MY, Rho MC, Ko JS, Ryu SY, Jeune KH, Kim K, Lee HS, Kim YK: In vitro inhibition of diacylglycerol acyltransferase by prenylflavonoids from Sophora flavescens. Planta Med. 2004 Mar;70(3):258-60. [PubMed:15114505 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Transferase activity, transferring acyl groups
Specific Function:
Plays a role in lipoprotein assembly and dietary cholesterol absorption. In addition to its acyltransferase activity, it may act as a ligase. May provide cholesteryl esters for lipoprotein secretion from hepatocytes and intestinal mucosa.
Gene Name:
SOAT2
Uniprot ID:
O75908
Molecular Weight:
59895.735 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. 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:10592235 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Breinholt VM, Offord EA, Brouwer C, Nielsen SE, Brosen K, Friedberg T: In vitro investigation of cytochrome P450-mediated metabolism of dietary flavonoids. Food Chem Toxicol. 2002 May;40(5):609-16. [PubMed:11955666 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular Weight:
72313.47 Da
References
  1. Zhang S, Yang X, Morris ME: Flavonoids are inhibitors of breast cancer resistance protein (ABCG2)-mediated transport. Mol Pharmacol. 2004 May;65(5):1208-16. [PubMed:15102949 ]
  2. Imai Y, Tsukahara S, Asada S, Sugimoto Y: Phytoestrogens/flavonoids reverse breast cancer resistance protein/ABCG2-mediated multidrug resistance. Cancer Res. 2004 Jun 15;64(12):4346-52. [PubMed:15205350 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23