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Identification
NameGriseofulvin
Accession NumberDB00400  (APRD01004)
Typesmall molecule
Groupsapproved
Description

An antifungal antibiotic. Griseofulvin may be given by mouth in the treatment of tinea infections. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
(+)-griseofulvinNot AvailableNot Available
AmudaneNot AvailableNot Available
GriseofulvinaSpanishINN
GriseofulvineFrenchINN
GriseofulvinumLatinINN
SaltsNot Available
Brand names
NameCompany
CrivicinNot Available
Curling factorNot Available
FulcinNot Available
FulvicinNot Available
GrifulvinNot Available
Grifulvin VOrthoneutrogena Labs
Gris-PEGNot Available
GrisactinNot Available
Grison-250Not Available
GrisovinNot Available
GrysioNot Available
LamorylNot Available
LikudenNot Available
PoncylNot Available
S-FulvinNot Available
SpirofulvinNot Available
SporostatinNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number126-07-8
WeightAverage: 352.766
Monoisotopic: 352.071365983
Chemical FormulaC17H17ClO6
InChI KeyInChIKey=DDUHZTYCFQRHIY-RBHXEPJQSA-N
InChI
InChI=1S/C17H17ClO6/c1-8-5-9(19)6-12(23-4)17(8)16(20)13-10(21-2)7-11(22-3)14(18)15(13)24-17/h6-8H,5H2,1-4H3/t8-,17+/m1/s1
IUPAC Name
(2S,6'R)-7-chloro-2',4,6-trimethoxy-6'-methyl-3H-spiro[1-benzofuran-2,1'-cyclohexan]-2'-ene-3,4'-dione
SMILES
COC1=CC(OC)=C(Cl)C2=C1C(=O)[C@]1(O2)[C@H](C)CC(=O)C=C1OC
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzofurans
SubclassNot Available
Direct parentBenzofurans
Alternative parentsAnisoles; Alkyl Aryl Ethers; Chlorobenzenes; Aryl Chlorides; Ketones; Polyamines; Organochlorides
Substituentsphenol ether; anisole; chlorobenzene; alkyl aryl ether; aryl halide; aryl chloride; benzene; ketone; polyamine; ether; carbonyl group; organochloride; organohalogen
Classification descriptionThis compound belongs to the benzofurans. These are organic compounds containing a benzene ring fused to a furan.
Pharmacology
IndicationFor the treatment of ringworm infections of the skin, hair, and nails, namely: tinea corporis, tinea pedis, tinea cruris, tinea barbae, cradle cap or other conditions caused by Trichophyton or Microsporum fungi.
PharmacodynamicsGriseofulvin is a mycotoxic metabolic product of Penicillium spp. It was the first available oral agent for the treatment of dermatophytoses and has now been used for more than forty years. Griseofulvin is fungistatic with in vitro activity against various species of Microsporum Epidermophyton, and Trichophyton. It has no effect on bacteria or on other genera of fungi. Following oral administration, griseofulvin is deposited in the keratin precursor cells and has a greater affinity for diseased tissue. The drug is tightly bound to the new keratin which becomes highly resistant to fungal invasions. Once the keratin-Griseofulvin complex reaches the skin site of action, it binds to fungal microtubules (tubulin) thus altering fungal mitosis.
Mechanism of actionGriseofulvin is fungistatic, however the exact mechanism by which it inhibits the growth of dermatophytes is not clear. It is thought to inhibit fungal cell mitosis and nuclear acid synthesis. It also binds to and interferes with the function of spindle and cytoplasmic microtubules by binding to alpha and beta tubulin. It binds to keratin in human cells, then once it reaches the fungal site of action, it binds to fungal microtubes thus altering the fungal process of mitosis.
AbsorptionPoorly absorbed from GI ranging from 25 to 70% of an oral dose. Absorption is significantly enhanced by administration with or after a fatty meal.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Primarily hepatic with major metabolites being 6-methyl-griseofulvin and its glucuronide conjugate.

SubstrateEnzymesProduct
Griseofulvin
    6-methyl-griseofulvinDetails
    Route of eliminationNot Available
    Half life9-21 hours
    ClearanceNot Available
    ToxicitySide effects are minor: headaches, gastrointestinal reactions and cutaneous eruptions
    Affected organisms
    • Yeast and other Trichophyton or Microsporum fungi
    PathwaysNot Available
    SNP Mediated EffectsNot Available
    SNP Mediated Adverse Drug ReactionsNot Available
    ADMET
    Predicted ADMET features
    Property Value Probability
    Human Intestinal Absorption + 1.0
    Blood Brain Barrier + 0.9208
    Caco-2 permeable + 0.8867
    P-glycoprotein substrate Substrate 0.612
    P-glycoprotein inhibitor I Inhibitor 0.8183
    P-glycoprotein inhibitor II Inhibitor 0.5133
    Renal organic cation transporter Non-inhibitor 0.882
    CYP450 2C9 substrate Non-substrate 0.7921
    CYP450 2D6 substrate Non-substrate 0.9117
    CYP450 3A4 substrate Substrate 0.6249
    CYP450 1A2 substrate Non-inhibitor 0.9046
    CYP450 2C9 substrate Non-inhibitor 0.9071
    CYP450 2D6 substrate Non-inhibitor 0.9231
    CYP450 2C19 substrate Non-inhibitor 0.9026
    CYP450 3A4 substrate Inhibitor 0.7043
    CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8235
    Ames test Non AMES toxic 0.9133
    Carcinogenicity Non-carcinogens 0.8544
    Biodegradation Not ready biodegradable 0.9964
    Rat acute toxicity 1.5788 LD50, mol/kg Not applicable
    hERG inhibition (predictor I) Weak inhibitor 0.938
    hERG inhibition (predictor II) Non-inhibitor 0.8869
    Pharmacoeconomics
    Manufacturers
    • Wyeth ayerst laboratories
    • Johnson and johnson consumer companies inc
    • Orthoneutrogena
    • Actavis mid atlantic llc
    • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
    • Perrigo co tennessee inc
    • Elorac inc
    • Johnson and johnson consumer products inc
    • Schering corp sub schering plough corp
    • Pedinol pharmacal inc
    • Pliva inc
    Packagers
    Dosage forms
    FormRouteStrength
    SuspensionOral
    TabletOral
    Prices
    Unit descriptionCostUnit
    Griseofulvin Microsize 125 mg/5ml Suspension 120ml Bottle43.0USDbottle
    Grifulvin v 500 mg tablet4.78USDtablet
    Gris-peg 250 mg tablet2.75USDtablet
    Gris-peg 125 mg tablet2.24USDtablet
    Griseofulvin powder2.2USDg
    DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
    PatentsNot Available
    Properties
    Statesolid
    Experimental Properties
    PropertyValueSource
    melting point220 °CPhysProp
    water solubility8.64 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
    logP2.18HANSCH,C ET AL. (1995)
    logS-4.61ADME Research, USCD
    Caco2 permeability-4.44ADME Research, USCD
    Predicted Properties
    PropertyValueSource
    water solubility5.04e-02 g/lALOGPS
    logP2.71ALOGPS
    logP2.17ChemAxon
    logS-3.8ALOGPS
    pKa (strongest acidic)17.69ChemAxon
    pKa (strongest basic)-4.3ChemAxon
    physiological charge0ChemAxon
    hydrogen acceptor count6ChemAxon
    hydrogen donor count0ChemAxon
    polar surface area71.06ChemAxon
    rotatable bond count3ChemAxon
    refractivity87.85ChemAxon
    polarizability34.25ChemAxon
    number of rings3ChemAxon
    bioavailability1ChemAxon
    rule of fiveYesChemAxon
    Ghose filterYesChemAxon
    Veber's ruleNoChemAxon
    MDDR-like ruleNoChemAxon
    Spectra
    SpectraNot Available
    References
    Synthesis Reference

    Gary Liversidge, “Methods of making and using novel griseofulvin compositions.” U.S. Patent US20070098805, issued May 03, 2007.

    US20070098805
    General ReferenceNot Available
    External Links
    ResourceLink
    KEGG DrugD00209
    KEGG CompoundC06686
    PubChem Compound441140
    PubChem Substance46508437
    ChemSpider389934
    BindingDB31775
    ChEBI27779
    ChEMBLCHEMBL562
    Therapeutic Targets DatabaseDAP000539
    PharmGKBPA449814
    Drug Product Database332259
    RxListhttp://www.rxlist.com/cgi/generic3/griseofulvin.htm
    Drugs.comhttp://www.drugs.com/cdi/griseofulvin-microsize.html
    PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/gri1190.shtml
    WikipediaGriseofulvin
    ATC CodesD01AA08D01BA01
    AHFS CodesNot Available
    PDB EntriesNot Available
    FDA labelshow(131 KB)
    MSDSshow(75.7 KB)
    Interactions
    Drug Interactions
    Drug
    AcenocoumarolGriseofulvin may decrease the anticoagulant effect of acenocoumarol.
    Acetylsalicylic acidGriseofulvin may decrease the efficacy of acetylsalicylic acid.
    AmobarbitalThe barbiturate, amobarbital, decreases the effect of griseofulvin.
    AnisindioneGriseofulvin may decrease the anticoagulant effect of anisindione.
    AprobarbitalThe barbiturate, aprobarbital, decreases the effect of griseofulvin.
    ButabarbitalThe barbiturate, butabarbital, decreases the effect of griseofulvin.
    ButalbitalThe barbiturate, butalbital, decreases the effect of griseofulvin.
    ButethalThe barbiturate, butethal, decreases the effect of griseofulvin.
    ChlorotrianiseneThe enzyme inducer, griseofulvin, decreases the effect of the hormone agent, chlorotrianisene.
    ClomifeneThe enzyme inducer, griseofulvin, decreases the effect of the hormone agent, clomifene.
    Conjugated EstrogensThe enzyme inducer, griseofulvin, decreases the effect of the hormone agent, conjugated estrogens.
    CyclosporineGriseofulvin decreases the effect of cyclosporine
    DicoumarolGriseofulvin may decrease the anticoagulant effect of dicumarol.
    DiethylstilbestrolThe enzyme inducer, griseofulvin, decreases the effect of the hormone agent, diethylstilbestrol.
    Dihydroquinidine barbiturateThe barbiturate, dihydroquinidine barbiturate, decreases the effect of griseofulvin.
    EstradiolThe enzyme inducer, griseofulvin, decreases the effect of the hormone agent, estradiol.
    EstriolThe enzyme inducer, griseofulvin, decreases the effect of the hormone agent, estriol.
    EstroneThe enzyme inducer, griseofulvin, decreases the effect of the hormone agent, estrone.
    EstropipateThe enzyme inducer, griseofulvin, decreases the effect of the hormone agent, estropipate.
    Ethinyl EstradiolThis product may cause a slight decrease of contraceptive effect
    HeptabarbitalThe barbiturate, heptabarbital, decreases the effect of griseofulvin.
    HexobarbitalThe barbiturate, hexobarbital, decreases the effect of griseofulvin.
    LiraglutideCmax may be increased.
    Medroxyprogesterone AcetateThe enzyme inducer, griseofulvin, may decrease the effect of the hormone, medroxyprogesterone.
    Megestrol acetateThe enzyme inducer, griseofulvin, may decrease the effect of the hormone, megestrol.
    MestranolThis product may cause a slight decrease of contraceptive effect
    MethohexitalThe barbiturate, methohexital, decreases the effect of griseofulvin.
    MethylphenobarbitalThe barbiturate, methylphenobarbital, decreases the effect of griseofulvin.
    NorethindroneThis product may cause a slight decrease of contraceptive effect
    PentobarbitalThe barbiturate, pentobarbital, decreases the effect of griseofulvin.
    PhenobarbitalThe barbiturate, phenobarbital, decreases the effect of griseofulvin.
    PrimidoneThe barbiturate, primidone, decreases the effect of griseofulvin.
    QuinestrolThe enzyme inducer, griseofulvin, decreases the effect of the hormone agent, quinestrol.
    Quinidine barbiturateThe barbiturate, quinidine barbiturate, decreases the effect of griseofulvin.
    SecobarbitalThe barbiturate, secobarbital, decreases the effect of griseofulvin.
    TalbutalThe barbiturate, talbutal, decreases the effect of griseofulvin.
    UlipristalConcomitant therapy with strong CYP3A4 inducers may decrease plasma concentrations of ulipristal and ultimately its effectiveness. Avoid combination therapy.
    WarfarinGriseofulvin may decrease the anticoagulant effect of warfarin.
    Food Interactions
    • Avoid alcohol.
    • Take this medication with a high fat meal, fatty foods increase bioavailability.

    1. Tubulin beta chain

    Kind: protein

    Organism: Yeast

    Pharmacological action: yes

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Tubulin beta chain P10875 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
    3. Czymmek KJ, Bourett TM, Shao Y, DeZwaan TM, Sweigard JA, Howard RJ: Live-cell imaging of tubulin in the filamentous fungus Magnaporthe grisea treated with anti-microtubule and anti-microfilament agents. Protoplasma. 2005 Apr;225(1-2):23-32. Epub 2005 May 4. Pubmed
    4. Kiso T, Fujita K, Ping X, Tanaka T, Taniguchi M: Screening for microtubule-disrupting antifungal agents by using a mitotic-arrest mutant of Aspergillus nidulans and novel action of phenylalanine derivatives accompanying tubulin loss. Antimicrob Agents Chemother. 2004 May;48(5):1739-48. Pubmed
    5. Wang L, Zhou HB, Frisvad JC, Samson RA: Penicillium persicinum, a new griseofulvin, chrysogine and roquefortine C producing species from Qinghai Province, China. Antonie Van Leeuwenhoek. 2004 Aug;86(2):173-9. Pubmed

    2. Tubulin alpha chain

    Kind: protein

    Organism: Yeast

    Pharmacological action: yes

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Tubulin alpha chain P87066 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

    3. Keratin, type I cytoskeletal 12

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: other/unknown

    Components

    Name UniProt ID Details
    Keratin, type I cytoskeletal 12 Q99456 Details

    References:

    1. Nakamichi I, Hatakeyama S, Nakayama KI: Formation of Mallory body-like inclusions and cell death induced by deregulated expression of keratin 18. Mol Biol Cell. 2002 Oct;13(10):3441-51. Pubmed
    2. Sobue S, Sekiguchi K, Nabeshima T: Intracutaneous distributions of fluconazole, itraconazole, and griseofulvin in Guinea pigs and binding to human stratum corneum. Antimicrob Agents Chemother. 2004 Jan;48(1):216-23. Pubmed

    1. Cytochrome P450 1A2

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inducer

    Components

    Name UniProt ID Details
    Cytochrome P450 1A2 P05177 Details

    References:

    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
    2. Rasmussen BB, Jeppesen U, Gaist D, Brosen K: Griseofulvin and fluvoxamine interactions with the metabolism of theophylline. Ther Drug Monit. 1997 Feb;19(1):56-62. Pubmed

    2. Cytochrome P450 3A4

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inducer

    Components

    Name UniProt ID Details
    Cytochrome P450 3A4 P08684 Details

    References:

    1. Yasuda K, Ranade A, Venkataramanan R, Strom S, Chupka J, Ekins S, Schuetz E, Bachmann K: A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine. Drug Metab Dispos. 2008 Aug;36(8):1689-97. Epub 2008 May 27. Pubmed

    Comments
    Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:10