You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameHyperforin
Accession NumberDB01892  (EXPT01804)
TypeSmall Molecule
GroupsNutraceutical
Description

Hyperforin is a phytochemical produced by some of the members of the plant genus Hypericum, notably Hypericum perforatum (St John’s wort).

Structure
Thumb
Synonyms
SynonymLanguageCode
HiperforinaNot AvailableNot Available
HyperforineNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
CAS number11079-53-1
WeightAverage: 536.785
Monoisotopic: 536.386560152
Chemical FormulaC35H52O4
InChI KeyIWBJJCOKGLUQIZ-UHFFFAOYSA-N
InChI
InChI=1S/C35H52O4/c1-22(2)13-12-19-33(11)27(16-14-23(3)4)21-34(20-18-25(7)8)30(37)28(17-15-24(5)6)31(38)35(33,32(34)39)29(36)26(9)10/h13-15,18,26-27,38H,12,16-17,19-21H2,1-11H3
IUPAC Name
4-hydroxy-6-methyl-1,3,7-tris(3-methylbut-2-en-1-yl)-6-(4-methylpent-3-en-1-yl)-5-(2-methylpropanoyl)bicyclo[3.3.1]non-3-ene-2,9-dione
SMILES
CC(C)C(=O)C12C(O)=C(CC=C(C)C)C(=O)C(CC=C(C)C)(CC(CC=C(C)C)C1(C)CCC=C(C)C)C2=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as bicyclic monoterpenoids. These are monoterpenoids containing exactly 2 rings, which are fused to each other.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassMonoterpenoids
Direct ParentBicyclic monoterpenoids
Alternative Parents
Substituents
  • Bicyclic monoterpenoid
  • Cyclohexanone
  • Vinylogous acid
  • Ketone
  • Enol
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationNot Available
PharmacodynamicsHyperforin is believed to be the primary active constituent responsible for the antidepressant and anxiolytic properties of the extracts of St. John's wort. It acts as a reuptake inhibitor of monoamines, including serotonin, norepinephrine, dopamine, and of GABA and glutamate, with IC50 values of 0.05-0.10 mcg/ml for all compounds, with the exception of glutamate, which is in the 0.5 mcg/ml range. It appears to exert these effects by activating the transient receptor potential ion channel TRPC6. Activation of TRPC6 induces the entry of sodium and calcium into the cell which causes inhibition of monoamine reuptake. Hyperforin is also thought to be responsible for the induction of the cytochrome P450 enzymes CYP3A4 and CYP2C9 by binding to and activating the pregnane X receptor (PXR).
Mechanism of actionHyperforin is believed to be the primary active constituent responsible for the antidepressant and anxiolytic properties of the extracts of St. John's wort. It acts as a reuptake inhibitor of monoamines, including serotonin, norepinephrine, dopamine, and of GABA and glutamate, with IC50 values of 0.05-0.10 mcg/ml for all compounds, with the exception of glutamate, which is in the 0.5 mcg/ml range. It appears to exert these effects by activating the transient receptor potential ion channel TRPC6. Activation of TRPC6 induces the entry of sodium and calcium into the cell which causes inhibition of monoamine reuptake.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life9 hours
ClearanceNot Available
ToxicityOral LD50 (rat):5628 mg/kg; Skin LD50 (rabbit): 15800 mg/kg; Subcutaneous LD50 (mouse):9800 mg/kg; Intraperitoneal LD50 (rabbit):1826 mg/kg
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9944
Blood Brain Barrier+0.8988
Caco-2 permeable+0.6793
P-glycoprotein substrateSubstrate0.752
P-glycoprotein inhibitor INon-inhibitor0.6801
P-glycoprotein inhibitor IIInhibitor0.874
Renal organic cation transporterNon-inhibitor0.7856
CYP450 2C9 substrateNon-substrate0.8001
CYP450 2D6 substrateNon-substrate0.9164
CYP450 3A4 substrateSubstrate0.7483
CYP450 1A2 substrateNon-inhibitor0.8383
CYP450 2C9 substrateNon-inhibitor0.7589
CYP450 2D6 substrateNon-inhibitor0.9451
CYP450 2C19 substrateNon-inhibitor0.8338
CYP450 3A4 substrateNon-inhibitor0.7402
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8192
Ames testNon AMES toxic0.8883
CarcinogenicityNon-carcinogens0.9275
BiodegradationNot ready biodegradable0.9758
Rat acute toxicity2.9007 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8802
hERG inhibition (predictor II)Non-inhibitor0.8842
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point70-80Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000632 mg/mLALOGPS
logP6.32ALOGPS
logP9.67ChemAxon
logS-5.9ALOGPS
pKa (Strongest Acidic)6.32ChemAxon
pKa (Strongest Basic)-6.6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area71.44 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity166.68 m3·mol-1ChemAxon
Polarizability64.09 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Chatterjee SS, Bhattacharya SK, Wonnemann M, Singer A, Muller WE: Hyperforin as a possible antidepressant component of hypericum extracts. Life Sci. 1998;63(6):499-510. Pubmed
  2. Leuner K, Kazanski V, Muller M, Essin K, Henke B, Gollasch M, Harteneck C, Muller WE: Hyperforin—a key constituent of St. John’s wort specifically activates TRPC6 channels. FASEB J. 2007 Dec;21(14):4101-11. Epub 2007 Jul 31. Pubmed
  3. Moore LB, Goodwin B, Jones SA, Wisely GB, Serabjit-Singh CJ, Willson TM, Collins JL, Kliewer SA: St. John’s wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7500-2. Pubmed
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSDownload (22.8 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Nuclear receptor subfamily 1 group I member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Nuclear receptor subfamily 1 group I member 2 O75469 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

2. Prostaglandin G/H synthase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 1 P23219 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Arachidonate 5-lipoxygenase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Arachidonate 5-lipoxygenase P09917 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Transporters

1. Canalicular multispecific organic anion transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 1 Q92887 Details

References:

  1. Kast HR, Goodwin B, Tarr PT, Jones SA, Anisfeld AM, Stoltz CM, Tontonoz P, Kliewer S, Willson TM, Edwards PA: Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J Biol Chem. 2002 Jan 25;277(4):2908-15. Epub 2001 Nov 12. Pubmed

2. Solute carrier organic anion transporter family member 1B1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1B1 Q9Y6L6 Details

References:

  1. Tirona RG, Leake BF, Wolkoff AW, Kim RB: Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J Pharmacol Exp Ther. 2003 Jan;304(1):223-8. Pubmed

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:16