Hesperetin
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Hesperetin
- DrugBank Accession Number
- DB01094
- Background
Hesperetin belongs to the flavanone class of flavonoids. Hesperetin, in the form of its glycoside hesperidin, is the predominant flavonoid in lemons and oranges.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
- Weight
- Average: 302.2788
Monoisotopic: 302.07903818 - Chemical Formula
- C16H14O6
- 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
- Hesperitin
- External IDs
- FEMA NO. 4313
- NSC-57654
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.
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- 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.
Target Actions Organism ADiacylglycerol O-acyltransferase 1 inhibitorHumans AMicrosomal triglyceride transfer protein large subunit antagonistHumans ASterol O-acyltransferase 1 inhibitorHumans USex hormone-binding globulin Not Available Humans USterol O-acyltransferase 2 inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Hover over products below to view reaction partners
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Hesperetin can be increased when it is combined with Abametapir. Abatacept The metabolism of Hesperetin can be increased when combined with Abatacept. Abemaciclib Hesperetin may decrease the excretion rate of Abemaciclib which could result in a higher serum level. Abiraterone The serum concentration of Hesperetin can be increased when it is combined with Abiraterone. Acenocoumarol The metabolism of Acenocoumarol can be decreased when combined with Hesperetin. - Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- 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
- 1-benzopyran / 1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / 3'-hydroxyflavonoid / 4p-methoxyflavonoid-skeleton / 5-hydroxyflavonoid / 7-hydroxyflavonoid / Alkyl aryl ether / Anisole / Aromatic heteropolycyclic compound show 24 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- 3'-hydroxyflavanones, trihydroxyflavanone, monomethoxyflavanone (CHEBI:28230) / flavanones (C01709) / Flavanones (LMPK12140003)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- Q9Q3D557F1
- CAS number
- 520-33-2
- 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)[C@@H]1CC(=O)C2=C(O)C=C(O)C=C2O1
References
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0005782
- KEGG Compound
- C01709
- PubChem Compound
- 72281
- PubChem Substance
- 46507998
- ChemSpider
- 65234
- BindingDB
- 23418
- 1314255
- ChEBI
- 28230
- ChEMBL
- CHEMBL399121
- ZINC
- ZINC000000039092
- Therapeutic Targets Database
- DAP001306
- PharmGKB
- PA164742902
- PDBe Ligand
- 6JP
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Hesperetin
- PDB Entries
- 5jdc / 7pou
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data0 Completed Basic Science Blood Glucose Fluctuations / Hunger 1 somestatus stop reason just information to hide 0 Recruiting Basic Science Blood Glucose Fluctuations / Hunger 1 somestatus stop reason just information to hide
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 (°C) 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 0.138 mg/mL ALOGPS logP 2.52 ALOGPS logP 2.68 Chemaxon logS -3.3 ALOGPS pKa (Strongest Acidic) 7.86 Chemaxon pKa (Strongest Basic) -4.6 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 96.22 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 77.75 m3·mol-1 Chemaxon Polarizability 29.3 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9511 Blood Brain Barrier - 0.6591 Caco-2 permeable + 0.8286 P-glycoprotein substrate Substrate 0.6682 P-glycoprotein inhibitor I Non-inhibitor 0.743 P-glycoprotein inhibitor II Inhibitor 0.5576 Renal organic cation transporter Non-inhibitor 0.8866 CYP450 2C9 substrate Non-substrate 0.7059 CYP450 2D6 substrate Non-substrate 0.863 CYP450 3A4 substrate Non-substrate 0.5067 CYP450 1A2 substrate Inhibitor 0.9106 CYP450 2C9 inhibitor Inhibitor 0.8949 CYP450 2D6 inhibitor Inhibitor 0.651 CYP450 2C19 inhibitor Inhibitor 0.8994 CYP450 3A4 inhibitor Inhibitor 0.7959 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7998 Ames test Non AMES toxic 0.8777 Carcinogenicity Non-carcinogens 0.9483 Biodegradation Not ready biodegradable 0.8978 Rat acute toxicity 3.1455 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9747 hERG inhibition (predictor II) Non-inhibitor 0.8574
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 186.7378311 predictedDarkChem Lite v0.1.0 [M-H]- 169.4228882 predictedDarkChem Standard v0.1.0 [M-H]- 186.6873311 predictedDarkChem Lite v0.1.0 [M-H]- 186.6053311 predictedDarkChem Lite v0.1.0 [M-H]- 168.50514 predictedDeepCCS 1.0 (2019) [M+H]+ 190.3248311 predictedDarkChem Lite v0.1.0 [M+H]+ 175.3408569 predictedDarkChem Standard v0.1.0 [M+H]+ 188.3213311 predictedDarkChem Lite v0.1.0 [M+H]+ 188.8842311 predictedDarkChem Lite v0.1.0 [M+H]+ 170.86314 predictedDeepCCS 1.0 (2019) [M+Na]+ 187.8313311 predictedDarkChem Lite v0.1.0 [M+Na]+ 174.7470478 predictedDarkChem Standard v0.1.0 [M+Na]+ 187.7043311 predictedDarkChem Lite v0.1.0 [M+Na]+ 187.6931311 predictedDarkChem Lite v0.1.0 [M+Na]+ 177.7159 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates (PubMed:16214399, PubMed:18768481, PubMed:28420705, PubMed:32433610, PubMed:32433611, PubMed:9756920). Highly expressed in epithelial cells of the small intestine and its activity is essential for the absorption of dietary fats (PubMed:18768481). In liver, plays a role in esterifying exogenous fatty acids to glycerol, and is required to synthesize fat for storage (PubMed:16214399). Also present in female mammary glands, where it produces fat in the milk (By similarity). May be involved in VLDL (very low density lipoprotein) assembly (PubMed:18768481). In contrast to DGAT2 it is not essential for survival (By similarity). Functions as the major acyl-CoA retinol acyltransferase (ARAT) in the skin, where it acts to maintain retinoid homeostasis and prevent retinoid toxicity leading to skin and hair disorders (PubMed:16214399). Exhibits additional acyltransferase activities, includin acyl CoA:monoacylglycerol acyltransferase (MGAT), wax monoester and wax diester synthases (By similarity). Also able to use 1-monoalkylglycerol (1-MAkG) as an acyl acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG) (PubMed:28420705)
- Specific Function
- 2-acylglycerol O-acyltransferase activity
- Gene Name
- DGAT1
- Uniprot ID
- O75907
- Uniprot Name
- Diacylglycerol O-acyltransferase 1
- Molecular Weight
- 55277.735 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces (PubMed:15897609, PubMed:16478722, PubMed:22236406, PubMed:23475612, PubMed:25108285, PubMed:26224785, PubMed:8876250, PubMed:8939939). Required for the assembly and secretion of plasma lipoproteins that contain apolipoprotein B (PubMed:16478722, PubMed:23475612, PubMed:26224785, PubMed:8876250, PubMed:8939939). May be involved in regulating cholesteryl ester biosynthesis in cells that produce lipoproteins (By similarity)
- Specific Function
- apolipoprotein binding
- Gene Name
- MTTP
- Uniprot ID
- P55157
- Uniprot Name
- Microsomal triglyceride transfer protein large subunit
- Molecular Weight
- 99350.255 Da
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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol (PubMed:16154994, PubMed:16647063, PubMed:32433613, PubMed:32433614, PubMed:32944968, PubMed:9020103). Plays a role in lipoprotein assembly and dietary cholesterol absorption (PubMed:16154994, PubMed:9020103). Preferentially utilizes oleoyl-CoA ((9Z)-octadecenoyl-CoA) as a substrate: shows a higher activity towards an acyl-CoA substrate with a double bond at the delta-9 position (9Z) than towards saturated acyl-CoA or an unsaturated acyl-CoA with a double bond at the delta-7 (7Z) or delta-11 (11Z) positions (PubMed:11294643, PubMed:32433614)
- Specific Function
- cholesterol binding
- Gene Name
- SOAT1
- Uniprot ID
- P35610
- Uniprot Name
- Sterol O-acyltransferase 1
- Molecular Weight
- 64733.975 Da
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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General 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, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration
- Specific Function
- androgen binding
- Gene Name
- SHBG
- Uniprot ID
- P04278
- Uniprot Name
- Sex hormone-binding globulin
- Molecular Weight
- 43778.755 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol (PubMed:11294643, PubMed:16647063). Plays a role in lipoprotein assembly and dietary cholesterol absorption (PubMed:11294643). Utilizes oleoyl-CoA ((9Z)-octadecenoyl-CoA) and linolenoyl-CoA ((9Z,12Z,15Z)-octadecatrienoyl-CoA) as substrates (PubMed:11294643). May provide cholesteryl esters for lipoprotein secretion from hepatocytes and intestinal mucosa (PubMed:11294643)
- Specific Function
- acyltransferase activity
- Gene Name
- SOAT2
- Uniprot ID
- O75908
- Uniprot Name
- Sterol O-acyltransferase 2
- Molecular Weight
- 59895.735 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
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. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
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. [Article]
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 03, 2024 04:26