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Identification
Name Griseofulvin
Accession Number DB00400 (APRD01004)
Type small molecule
Groups approved
Description

An antifungal antibiotic. Griseofulvin may be given by mouth in the treatment of tinea infections. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Griseofulvina [INN-Spanish]
Griseofulvine [INN-French]
Griseofulvinum [INN-Latin]
Salts Not Available
Brand names
Name Company
Amudane
Biogrisin-fp
Curling factor
Delmofulvina
Fulcin
Fulcine
Fulvican grisactin
Fulvicin
Fulvicin P/G
Fulvicin U/F
Fulvicin-P/G
Fulvicin-U/F
Fulvina
Fulvinil
Fulvistatin
Fungivin
Greosin
Gresfeed
Gricin
Grifulin
Grifulvin
Grifulvin V
Gris-PEG
Grisactin
Grisactin Ultra
Griscofulvin
Grisefuline
Griseo
Griseofulvin forte
Griseofulvin-forte
Griseomix
Grisetin
Grisofulvin
Grisovin
Grisovin FP
Grizeofulvin
Grysio
Guservin
Lamoryl
Likuden
Likunden
Murfulvin
Neo-Fulcin
Neocid
Poncyl
Spirofulvin
Sporostatin
Sporostatin xan
Xuanjing
First Prev Next Last
Brand mixtures Not Available
Categories
  • Antibiotics, Antifungal
  • Antibacterial Agents
CAS number 126-07-8
Weight Average: 352.766
Monoisotopic: 352.071365983
Chemical Formula C17H17ClO6
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzofurans
  • Phenols and Derivatives
  • Ethers
  • Anisoles
  • Benzoyl Derivatives
Substructures
  • Benzofurans
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Benzoyl Derivatives
  • Cyclohexenes and Derivatives
  • Phenyl Esters
  • Ketones
Pharmacology
Indication For 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.
Pharmacodynamics Griseofulvin 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 action Griseofulvin 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.
Absorption Poorly 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 distribution Not Available
Protein binding Not Available
Metabolism Primarily hepatic with major metabolites being 6-methyl-griseofulvin and its glucuronide conjugate.
Route of elimination Not Available
Half life 9-21 hours
Clearance Not Available
Toxicity Side effects are minor: headaches, gastrointestinal reactions and cutaneous eruptions
Affected organisms
  • Yeast and other Trichophyton or Microsporum fungi
Pathways Not Available
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
Form Route Strength
Suspension Oral
Tablet Oral
Prices
Unit description Cost Unit
Griseofulvin Microsize 125 mg/5ml Suspension 120ml Bottle 43.0 USD bottle
Grifulvin v 500 mg tablet 4.78 USD tablet
Gris-peg 250 mg tablet 2.75 USD tablet
Gris-peg 125 mg tablet 2.24 USD tablet
Griseofulvin powder 2.2 USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 220 °C PhysProp
water solubility 8.64 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP 2.18 HANSCH,C ET AL. (1995)
logS -4.61 ADME Research, USCD
Caco2 permeability -4.44 ADME Research, USCD
Predicted Properties
Property Value Source
water solubility 5.04e-02 g/l ALOGPS
logP 2.71 ALOGPS
logP 2.17 ChemAxon
logS -3.8 ALOGPS
pKa (strongest acidic) 17.69 ChemAxon
pKa (strongest basic) -4.3 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 6 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 71.06 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 87.85 ChemAxon
polarizability 34.25 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00209 Link_out
KEGG Compound C06686 Link_out
PubChem Compound 441140 Link_out
PubChem Substance 46508437 Link_out
ChemSpider 389934 Link_out
BindingDB 31775 Link_out
ChEBI 27779 Link_out
ChEMBL 27779 Link_out
Therapeutic Targets Database DAP000539 Link_out
PharmGKB PA449814 Link_out
Drug Product Database 332259 Link_out
RxList http://www.rxlist.com/cgi/generic3/griseofulvin.htm Link_out
Drugs.com http://www.drugs.com/cdi/griseofulvin-microsize.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/gri1190.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Griseofulvin Link_out
ATC Codes
  • D01AA08
  • D01BA01
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (131 KB)
MSDS show (75.7 KB)
Interactions
Drug Interactions
Drug Interaction
Acenocoumarol Griseofulvin may decrease the anticoagulant effect of acenocoumarol.
Acetylsalicylic acid Griseofulvin may decrease the efficacy of acetylsalicylic acid.
Amobarbital The barbiturate, amobarbital, decreases the effect of griseofulvin.
Anisindione Griseofulvin may decrease the anticoagulant effect of anisindione.
Aprobarbital The barbiturate, aprobarbital, decreases the effect of griseofulvin.
Butabarbital The barbiturate, butabarbital, decreases the effect of griseofulvin.
Butalbital The barbiturate, butalbital, decreases the effect of griseofulvin.
Butethal The barbiturate, butethal, decreases the effect of griseofulvin.
Chlorotrianisene The enzyme inducer, griseofulvin, decreases the effect of the hormone agent, chlorotrianisene.
Clomifene The enzyme inducer, griseofulvin, decreases the effect of the hormone agent, clomifene.
Conjugated Estrogens The enzyme inducer, griseofulvin, decreases the effect of the hormone agent, conjugated estrogens.
Cyclosporine Griseofulvin decreases the effect of cyclosporine
Dicumarol Griseofulvin may decrease the anticoagulant effect of dicumarol.
Diethylstilbestrol The enzyme inducer, griseofulvin, decreases the effect of the hormone agent, diethylstilbestrol.
Dihydroquinidine barbiturate The barbiturate, dihydroquinidine barbiturate, decreases the effect of griseofulvin.
Estradiol The enzyme inducer, griseofulvin, decreases the effect of the hormone agent, estradiol.
Estriol The enzyme inducer, griseofulvin, decreases the effect of the hormone agent, estriol.
Estrone The enzyme inducer, griseofulvin, decreases the effect of the hormone agent, estrone.
Estropipate The enzyme inducer, griseofulvin, decreases the effect of the hormone agent, estropipate.
Ethinyl Estradiol This product may cause a slight decrease of contraceptive effect
Heptabarbital The barbiturate, heptabarbital, decreases the effect of griseofulvin.
Hexobarbital The barbiturate, hexobarbital, decreases the effect of griseofulvin.
Medroxyprogesterone The enzyme inducer, griseofulvin, may decrease the effect of the hormone, medroxyprogesterone.
Megestrol The enzyme inducer, griseofulvin, may decrease the effect of the hormone, megestrol.
Mestranol This product may cause a slight decrease of contraceptive effect
Methohexital The barbiturate, methohexital, decreases the effect of griseofulvin.
Methylphenobarbital The barbiturate, methylphenobarbital, decreases the effect of griseofulvin.
Norethindrone This product may cause a slight decrease of contraceptive effect
Pentobarbital The barbiturate, pentobarbital, decreases the effect of griseofulvin.
Phenobarbital The barbiturate, phenobarbital, decreases the effect of griseofulvin.
Primidone The barbiturate, primidone, decreases the effect of griseofulvin.
Quinestrol The enzyme inducer, griseofulvin, decreases the effect of the hormone agent, quinestrol.
Quinidine barbiturate The barbiturate, quinidine barbiturate, decreases the effect of griseofulvin.
Secobarbital The barbiturate, secobarbital, decreases the effect of griseofulvin.
Talbutal The barbiturate, talbutal, decreases the effect of griseofulvin.
Ulipristal Concomitant therapy with strong CYP3A4 inducers may decrease plasma concentrations of ulipristal and ultimately its effectiveness. Avoid combination therapy.
Warfarin Griseofulvin may decrease the anticoagulant effect of warfarin.
Food Interactions
  • Avoid alcohol.
  • Take this medication with a high fat meal, fatty foods increase bioavailability.
Targets

1. Tubulin beta chain

Pharmacological action: yes
Actions: inhibitor

Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha-chain

Organism class: fungal
UniProt ID: P10875 Link_out
Gene: TUB2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha-chain

Organism class: fungal
UniProt ID: P87066 Link_out
Gene: TUB1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: other/unknown
UniProt ID: Q99456 Link_out
Gene: KRT12
SNPs: SNPJam Report Link_out

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
Enzymes

1. Cytochrome P450 1A2

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 February 08, 2013 16:19