Hyperforin
Identification
- Generic Name
- Hyperforin
- DrugBank Accession Number
- DB01892
- Background
Hyperforin is a phytochemical generated by the plants of the Hypericum family. One of the most important members of this family, due to its medical properties, is Hypericum perforatum, also known as St John's wort.
- Type
- Small Molecule
- Groups
- Nutraceutical
- Structure
- Weight
- Average: 536.797
Monoisotopic: 536.386560154 - Chemical Formula
- C35H52O4
- Synonyms
- Hiperforina
- Hyperforine
Pharmacology
- Indication
Not Available
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- 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.
Target Actions Organism UNuclear receptor subfamily 1 group I member 2 Not Available Humans UProstaglandin G/H synthase 1 inhibitorHumans UArachidonate 5-lipoxygenase inhibitorHumans - 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
- Adverse Effects
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- 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
- 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 softwareAmbrisentan The excretion of Ambrisentan can be decreased when combined with Hyperforin. Asunaprevir The excretion of Asunaprevir can be decreased when combined with Hyperforin. Atogepant The serum concentration of Atogepant can be increased when it is combined with Hyperforin. Atorvastatin The excretion of Atorvastatin can be decreased when combined with Hyperforin. Axitinib The excretion of Axitinib can be decreased when combined with Hyperforin. - Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- 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
- Aliphatic homopolycyclic compound / Bicyclic monoterpenoid / Carbonyl group / Cyclohexenone / Enol / Hydrocarbon derivative / Ketone / Organic oxide / Organic oxygen compound / Organooxygen compound
- Molecular Framework
- Aliphatic homopolycyclic compounds
- External Descriptors
- carbobicyclic compound, cyclic terpene ketone, sesquarterpenoid (CHEBI:5834)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- RM741E34FP
- CAS number
- 11079-53-1
- 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)[C@@]12C(O)=C(CC=C(C)C)C(=O)[C@@](CC=C(C)C)(C[C@H](CC=C(C)C)[C@@]1(C)CCC=C(C)C)C2=O
References
- General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- External Links
- KEGG Compound
- C07608
- PubChem Compound
- 441298
- PubChem Substance
- 46506104
- ChemSpider
- 16736597
- BindingDB
- 50193079
- ChEBI
- 5834
- ChEMBL
- CHEMBL1237210
- ZINC
- ZINC000004097413
- Therapeutic Targets Database
- DNC000759
- PDBe Ligand
- HYF
- Wikipedia
- Hyperforin
- MSDS
- Download (22.8 KB)
Clinical Trials
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) 70-80 Not Available - Predicted Properties
Property Value Source Water Solubility 0.000632 mg/mL ALOGPS logP 6.32 ALOGPS logP 9.67 Chemaxon logS -5.9 ALOGPS pKa (Strongest Acidic) 3.62 Chemaxon pKa (Strongest Basic) -7.3 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 71.44 Å2 Chemaxon Rotatable Bond Count 11 Chemaxon Refractivity 166.68 m3·mol-1 Chemaxon Polarizability 63.75 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9944 Blood Brain Barrier + 0.8988 Caco-2 permeable + 0.6793 P-glycoprotein substrate Substrate 0.752 P-glycoprotein inhibitor I Non-inhibitor 0.6801 P-glycoprotein inhibitor II Inhibitor 0.874 Renal organic cation transporter Non-inhibitor 0.7856 CYP450 2C9 substrate Non-substrate 0.8001 CYP450 2D6 substrate Non-substrate 0.9164 CYP450 3A4 substrate Substrate 0.7483 CYP450 1A2 substrate Non-inhibitor 0.8383 CYP450 2C9 inhibitor Non-inhibitor 0.7589 CYP450 2D6 inhibitor Non-inhibitor 0.9451 CYP450 2C19 inhibitor Non-inhibitor 0.8338 CYP450 3A4 inhibitor Non-inhibitor 0.7402 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8192 Ames test Non AMES toxic 0.8883 Carcinogenicity Non-carcinogens 0.9275 Biodegradation Not ready biodegradable 0.9758 Rat acute toxicity 2.9007 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8802 hERG inhibition (predictor II) Non-inhibitor 0.8842
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 253.3970113 predictedDarkChem Lite v0.1.0 [M-H]- 240.9426 predictedDeepCCS 1.0 (2019) [M+H]+ 255.1030113 predictedDarkChem Lite v0.1.0 [M+H]+ 243.10524 predictedDeepCCS 1.0 (2019) [M+Na]+ 253.6860113 predictedDarkChem Lite v0.1.0 [M+Na]+ 248.84563 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- 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
- Kind
- Protein
- Organism
- Humans
- 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
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- 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
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at January 07, 2021 03:10