DrugBank: Hesperetin (DB01094)

targets (3) enzymes (1) transporters (1)

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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Cyanidanon 4'-Methyl Ether 1626
Hesperitin
YSO2

Salts

Not Available

Brand names

Name	Company
Hesperin

Brand mixtures

Not Available

Categories

Anticholesteremic Agents

CAS number

520-33-2

Weight

Average: 302.2788
Monoisotopic: 302.07903818

Chemical Formula

C₁₆H₁₄O₆

InChI Key

InChIKey=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

Plain Text

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

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Flavanones

Substructures

Hydroxy Compounds
Pyrans
Benzyl Alcohols and Derivatives
Phenols and Derivatives
Ethers
Flavanones
Benzene and Derivatives
Chromones
Methoxyphenols
Benzopyrans
Catechols
Heterocyclic compounds
Aromatic compounds
Anisoles
Benzoyl Derivatives
Phenyl Esters
Resorcinols
Ketones

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.

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.

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Not Available

Half life

Not Available

Clearance

Not Available

Toxicity

Not Available

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Not Available

Prices

Not Available

Patents

Not Available

Properties

State

solid

Experimental Properties

Property	Value	Source
melting point	227.5 °C	PhysProp
water solubility	273 mg/L	Not Available
logP	2.60	PERRISSOUD,D & TESTA,B (1986)

Predicted Properties

Property	Value	Source
water solubility	1.38e-01 g/l	ALOGPS
logP	2.52	ALOGPS
logP	2.68	ChemAxon
logS	-3.3	ALOGPS
pKa (strongest acidic)	7.92	ChemAxon
pKa (strongest basic)	-3.9	ChemAxon
physiological charge	0	ChemAxon
hydrogen acceptor count	6	ChemAxon
hydrogen donor count	3	ChemAxon
polar surface area	96.22	ChemAxon
rotatable bond count	2	ChemAxon
refractivity	77.75	ChemAxon
polarizability	29.3	ChemAxon

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Compound	C01709
PubChem Compound	72281
PubChem Substance	46507998
ChemSpider	65234
BindingDB	23418
ChEBI	28230
ChEMBL	28230
Therapeutic Targets Database	DAP001306
PharmGKB	PA164742902
PDRhealth	http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/hes_0318.shtml
Wikipedia	http://en.wikipedia.org/wiki/Hesperetin

ATC Codes

Not Available

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. Sterol O-acyltransferase 1 Pharmacological action: yes Actions: inhibitor Catalyzes the formation of fatty acid-cholesterol esters. Plays a role in lipoprotein assembly and dietary cholesterol absorption. In addition to its acyltransferase activity, it may act as a ligase Organism class: human UniProt ID: P35610 Gene: SOAT1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 2. Sterol O-acyltransferase 2 Pharmacological action: unknown Actions: inhibitor Organism class: human UniProt ID: O75908 Gene: SOAT2 SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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 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 3. Microsomal triglyceride transfer protein large subunit Pharmacological action: yes Actions: antagonist Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces. Required for the secretion of plasma lipoproteins that contain apolipoprotein B Organism class: human UniProt ID: P55157 Gene: MTTP Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Targets

1. Sterol O-acyltransferase 1

Pharmacological action: yes
Actions: inhibitor

Catalyzes the formation of fatty acid-cholesterol esters. Plays a role in lipoprotein assembly and dietary cholesterol absorption. In addition to its acyltransferase activity, it may act as a ligase

Organism class: human
UniProt ID: P35610 Link_out

Gene: SOAT1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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

2. Sterol O-acyltransferase 2

Pharmacological action: unknown
Actions: inhibitor
Organism class: human
UniProt ID: O75908 Link_out

Gene: SOAT2
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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
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

3. Microsomal triglyceride transfer protein large subunit

Pharmacological action: yes
Actions: antagonist

Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces. Required for the secretion of plasma lipoproteins that contain apolipoprotein B

Organism class: human
UniProt ID: P55157 Link_out

Gene: MTTP Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Enzymes
1. Cytochrome P450 1A2 Actions: substrate 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 N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen UniProt ID: P05177 Gene: CYP1A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Enzymes

1. Cytochrome P450 1A2

Actions: substrate

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 N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out

Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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 Actions: inhibitor Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123 UniProt ID: Q9UNQ0 Gene: ABCG2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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

Transporters

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

Actions: inhibitor

Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123

UniProt ID: Q9UNQ0 Link_out

Gene: ABCG2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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

Comments

Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19