Identification

Name
Hyperforin
Accession Number
DB01892  (EXPT01804)
Type
Small Molecule
Groups
Nutraceutical
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
  • Hiperforina
  • Hyperforine
Categories
UNII
RM741E34FP
CAS number
11079-53-1
Weight
Average: 536.797
Monoisotopic: 536.386560154
Chemical Formula
C35H52O4
InChI Key
IWBJJCOKGLUQIZ-HQKKAZOISA-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/t27-,33+,34+,35-/m0/s1
IUPAC Name
(1R,5S,6R,7S)-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)[[email protected]@]12C(O)=C(CC=C(C)C)C(=O)[[email protected]@](CC=C(C)C)(C[[email protected]](CC=C(C)C)[[email protected]@]1(C)CCC=C(C)C)C2=O

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics

Hyperforin 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 action

Hyperforin 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.

TargetActionsOrganism
UNuclear receptor subfamily 1 group I member 2Not AvailableHuman
UProstaglandin G/H synthase 1
inhibitor
Human
UArachidonate 5-lipoxygenase
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

9 hours

Clearance
Not Available
Toxicity

Oral LD50 (rat):5628 mg/kg; Skin LD50 (rabbit): 15800 mg/kg; Subcutaneous LD50 (mouse):9800 mg/kg; Intraperitoneal LD50 (rabbit):1826 mg/kg

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  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:9718074]
  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:17666455]
  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:10852961]
External Links
KEGG Compound
C07608
PubChem Compound
441298
PubChem Substance
46506104
ChemSpider
16736597
ChEBI
5834
Therapeutic Targets Database
DNC000759
HET
HYF
Wikipedia
Hyperforin
MSDS
Download (22.8 KB)

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)70-80Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000632 mg/mLALOGPS
logP6.32ALOGPS
logP9.67ChemAxon
logS-5.9ALOGPS
pKa (Strongest Acidic)3.82ChemAxon
pKa (Strongest Basic)-7.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area71.44 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity166.68 m3·mol-1ChemAxon
Polarizability63.59 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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 inhibitorNon-inhibitor0.7589
CYP450 2D6 inhibitorNon-inhibitor0.9451
CYP450 2C19 inhibitorNon-inhibitor0.8338
CYP450 3A4 inhibitorNon-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
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 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

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Prenol lipids
Sub Class
Monoterpenoids
Direct Parent
Bicyclic monoterpenoids
Alternative Parents
Cyclohexenones / Vinylogous acids / Enols / Organic oxides / Hydrocarbon derivatives
Substituents
Bicyclic monoterpenoid / Cyclohexenone / Vinylogous acid / Ketone / Enol / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organooxygen compound / Carbonyl group
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
carbobicyclic compound, cyclic terpene ketone, sesquarterpenoid (CHEBI:5834)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Iron ion binding
Specific Function
Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Gene Name
ALOX5
Uniprot ID
P09917
Uniprot Name
Arachidonate 5-lipoxygenase
Molecular Weight
77982.595 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
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:11706036]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
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:12490595]

Drug created on June 13, 2005 07:24 / Updated on November 09, 2017 03:06