Identification

Name
Hesperetin
Accession Number
DB01094  (APRD00117)
Type
Small Molecule
Groups
Approved
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
  • (-)-(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 IDs
FEMA NO. 4313 / NSC-57654
International/Other Brands
Hesperin
Categories
UNII
Q9Q3D557F1
CAS number
520-33-2
Weight
Average: 302.2788
Monoisotopic: 302.07903818
Chemical Formula
C16H14O6
InChI Key
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)[[email protected]@H]1CC(=O)C2=C(O)C=C(O)C=C2O1

Pharmacology

Indication

For 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.

Structured Indications
Not Available
Pharmacodynamics

Hesperetin 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 action

Hesperetin 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.

TargetActionsOrganism
AMicrosomal triglyceride transfer protein large subunit
antagonist
Human
ASterol O-acyltransferase 1
inhibitor
Human
USterol O-acyltransferase 2
inhibitor
Human
USex hormone-binding globulinNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Hesperetin can be increased when it is combined with Abiraterone.Approved
AzithromycinThe metabolism of Hesperetin can be decreased when combined with Azithromycin.Approved
BortezomibThe metabolism of Hesperetin can be decreased when combined with Bortezomib.Approved, Investigational
CaffeineThe metabolism of Hesperetin can be decreased when combined with Caffeine.Approved
CitalopramThe metabolism of Hesperetin can be decreased when combined with Citalopram.Approved
ClotrimazoleThe metabolism of Hesperetin can be decreased when combined with Clotrimazole.Approved, Vet Approved
Cyproterone acetateThe serum concentration of Hesperetin can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DeferasiroxThe serum concentration of Hesperetin can be increased when it is combined with Deferasirox.Approved, Investigational
DosulepinThe metabolism of Hesperetin can be decreased when combined with Dosulepin.Approved
FluvoxamineThe metabolism of Hesperetin can be decreased when combined with Fluvoxamine.Approved, Investigational
LidocaineThe metabolism of Hesperetin can be decreased when combined with Lidocaine.Approved, Vet Approved
LobeglitazoneThe metabolism of Hesperetin can be decreased when combined with Lobeglitazone.Approved, Investigational
MexiletineThe metabolism of Hesperetin can be decreased when combined with Mexiletine.Approved
MidostaurinThe metabolism of Hesperetin can be decreased when combined with Midostaurin.Approved
NevirapineThe metabolism of Hesperetin can be decreased when combined with Nevirapine.Approved
OsimertinibThe serum concentration of Hesperetin can be decreased when it is combined with Osimertinib.Approved
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Hesperetin.Approved
Peginterferon alfa-2bThe serum concentration of Hesperetin can be increased when it is combined with Peginterferon alfa-2b.Approved
RopiniroleThe metabolism of Hesperetin can be decreased when combined with Ropinirole.Approved, Investigational
SimeprevirThe metabolism of Hesperetin can be decreased when combined with Simeprevir.Approved
Tenofovir disoproxilThe metabolism of Hesperetin can be decreased when combined with Tenofovir disoproxil.Approved, Investigational
TeriflunomideThe serum concentration of Hesperetin can be decreased when it is combined with Teriflunomide.Approved
TheophyllineThe metabolism of Hesperetin can be decreased when combined with Theophylline.Approved
TiclopidineThe metabolism of Hesperetin can be decreased when combined with Ticlopidine.Approved
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Hesperetin.Approved, Investigational
VemurafenibThe serum concentration of Hesperetin can be increased when it is combined with Vemurafenib.Approved
ZucapsaicinThe metabolism of Hesperetin can be decreased when combined with Zucapsaicin.Approved
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB05782
KEGG Compound
C01709
PubChem Compound
72281
PubChem Substance
46507998
ChemSpider
65234
BindingDB
23418
ChEBI
28230
ChEMBL
CHEMBL399121
Therapeutic Targets Database
DAP001306
PharmGKB
PA164742902
HET
6JP
PDRhealth
PDRhealth Drug Page
Wikipedia
Hesperetin
PDB Entries
5jdc

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)227.5 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - ESI-TOF 10V, NegativeLC-MS/MSNot Available
MS/MS Spectrum - ESI-TOF 20V, NegativeLC-MS/MSNot Available
MS/MS Spectrum - ESI-TOF 40V, NegativeLC-MS/MSNot Available
MS/MS Spectrum - ESI-TOF , NegativeLC-MS/MSNot Available
MS/MS Spectrum - ESI-TOF 10V, NegativeLC-MS/MSNot Available
MS/MS Spectrum - ESI-TOF 30V, NegativeLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-0udi-0009000000-2a5462077f9208908972
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-0udi-0139000000-0c743a741d25379011aa
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-0w2i-0961000000-8406f0210238c955e23e
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-0gw0-0920000000-b833f9a80eb4ea8d3b13
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-052r-0910000000-943c442894f2e6d36fe3
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-0zfr-0925000000-20d9733844b315a5aac1
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-0f7c-0092000000-df166f951c1d37996e32
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-0f79-0092000000-28f5918da43818b380bf
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0009000000-fda4f743655d07e229dd
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0ufr-0906000000-4ff368578ae1225967b0
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0ufr-0900000000-aaca372b112b1730d913
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0900000000-8857224e3cadbbf71a7d
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0900000000-4507636d98e7b6ebd382
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-004i-0910000000-075f5279e98a14a60a55
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-004i-0910000000-1d9d4c851e8b474cffbe
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-2910000000-54a5cf5acd3ca156389e
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Flavonoids
Sub Class
O-methylated flavonoids
Direct Parent
4'-O-methylated flavonoids
Alternative Parents
3'-hydroxyflavonoids / 5-hydroxyflavonoids / 7-hydroxyflavonoids / Flavanones / Chromones / Methoxyphenols / Methoxybenzenes / Aryl alkyl ketones / Anisoles / Phenoxy compounds
show 7 more
Substituents
4p-methoxyflavonoid-skeleton / Flavanone / Hydroxyflavonoid / 7-hydroxyflavonoid / 5-hydroxyflavonoid / 3'-hydroxyflavonoid / Flavan / Chromone / Chromane / Benzopyran
show 24 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
3'-hydroxyflavanones, trihydroxyflavanone, monomethoxyflavanone (CHEBI:28230) / flavanones (C01709) / Flavanones (LMPK12140003)

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). Requ...
Gene Name
MTTP
Uniprot ID
P55157
Uniprot Name
Microsomal triglyceride transfer protein large subunit
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 ...
Gene Name
SOAT1
Uniprot ID
P35610
Uniprot Name
Sterol O-acyltransferase 1
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 secretio...
Gene Name
SOAT2
Uniprot ID
O75908
Uniprot Name
Sterol O-acyltransferase 2
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Androgen binding
Specific Function
Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone...
Gene Name
SHBG
Uniprot ID
P04278
Uniprot Name
Sex hormone-binding globulin
Molecular Weight
43778.755 Da
References
  1. Hong H, Branham WS, Ng HW, Moland CL, Dial SL, Fang H, Perkins R, Sheehan D, Tong W: Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and alpha-fetoprotein. Toxicol Sci. 2015 Feb;143(2):333-48. doi: 10.1093/toxsci/kfu231. Epub 2014 Oct 27. [PubMed:25349334]

Enzymes

Details
1. Cytochrome P450 1A2
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
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 fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
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]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:46