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Identification
NameHesperetin
Accession NumberDB01094  (APRD00117)
TypeSmall Molecule
GroupsApproved
Description

Hesperetin 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
SynonymLanguageCode
(-)-(S)-HesperetinNot AvailableNot Available
(-)-HesperetinNot AvailableNot Available
(S)-2,3-dihydro-5,7-Dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-1-benzopyran-4-oneNot AvailableNot Available
3',5,7-Trihydroxy-4'-methoxyflavanoneNot AvailableNot Available
Cyanidanon 4'-Methyl Ether 1626Not AvailableNot Available
HesperetinNot AvailableNot Available
HesperitinNot AvailableNot Available
YSO2Not AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
HesperinNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
CAS number520-33-2
WeightAverage: 302.2788
Monoisotopic: 302.07903818
Chemical FormulaC16H14O6
InChI KeyAIONOLUJZLIMTK-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.
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 substrateInhibitor0.8949
CYP450 2D6 substrateInhibitor0.651
CYP450 2C19 substrateInhibitor0.8994
CYP450 3A4 substrateInhibitor0.7959
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
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
Spectra1D NMR
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Microsomal triglyceride transfer protein large subunit

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Microsomal triglyceride transfer protein large subunit P55157 Details

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

2. Sterol O-acyltransferase 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sterol O-acyltransferase 1 P35610 Details

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
  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

3. Sterol O-acyltransferase 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Sterol O-acyltransferase 2 O75908 Details

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
  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
  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

Enzymes

1. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

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

Transporters

1. ATP-binding cassette sub-family G member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

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
  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

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