GRISEOFULVIN

First approved in 1959

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H17ClO6
Molecular Weight	352.766
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC(OC)=C2C(=O)[C@]3(OC2=C1Cl)[C@H](C)CC(=O)C=C3OC

InChI

InChIKey=DDUHZTYCFQRHIY-RBHXEPJQSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00400
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/050475s057lbl.pdf

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. 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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Candida albicans growth 2 Target ID: Candida albicans growth Sources: https://www.ncbi.nlm.nih.gov/pubmed/26900659	Inhibitor 8297
Aspergillus fumigatus growth 1 Target ID: Aspergillus fumigatus growth Sources: https://www.ncbi.nlm.nih.gov/pubmed/26900659	Inhibitor 8297
Fungi growth 1 Target ID: Fungi growth Sources: https://www.ncbi.nlm.nih.gov/pubmed/26369643	Inhibitor 8297
Tubulin alpha chain 3 Target ID: P87066 Gene ID: NA Gene Symbol: TUB1 Target Organism: Candida albicans (Yeast) Sources: http://www.drugbank.ca/drugs/DB00400	Inhibitor 8297
Staphylococcus aureus growth 27 Target ID: Staphylococcus aureus growth Sources: https://www.ncbi.nlm.nih.gov/pubmed/25103127	Inhibitor 8297
Tubulin beta chain 8 Target ID: P10875 Gene ID: NA Gene Symbol: TUB2 Target Organism: Candida albicans (Yeast) Sources: http://www.drugbank.ca/drugs/DB00400	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Dermatophyte infection 18 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/050475s057lbl.pdf	Curative		Approved 8429	GRIS-PEG Approved Use Gris-PEG® (griseofulvin ultramicrosize) is indicated for the treatment of the following ringworm infections; tinea corporis (ringworm of the body), tinea pedis (athlete’s foot), tinea cruris (ringworm of the groin and thigh), tinea barbae (barber’s itch), tinea capitis (ringworm of the scalp), and tinea unguium (onychomycosis, ringworm of the nails), when caused by one or more of the following genera of fungi: Trichophyton rubrum, Trichophyton tonsurans, Trichophyton mentagrophytes, Trichophyton interdigitalis,Trichophyton verrucosum, Trichophyton megnini, Trichophyton gallinae, Trichophyton crateriform, Trichophyton sulphureum, Trichophyton schoenleini, Microsporum audouini, Microsporum canis, Microsporum gypseum and Epidermophyton floccosum Launch Date 1.66751994E11

C_max

Value	Dose	Analyte	Population
629.77 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/065200_ORIGINAL%20APPROVAL_PACKAGE.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	GRISEOFULVIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1310.28 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/065200_ORIGINAL%20APPROVAL_PACKAGE.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	GRISEOFULVIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1.39 μg/mL EXPERIMENT https://link.springer.com/article/10.1007/BF00547378	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	GRISEOFULVIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1.25 μg/mL EXPERIMENT https://link.springer.com/article/10.1007/BF00547378	330 mg single, oral dose: 330 mg route of administration: Oral experiment type: SINGLE co-administered:	GRISEOFULVIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
600.61 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/050475s057lbl.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	GRISEOFULVIN unknown	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Analyte	Population
18827.7 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/065200_ORIGINAL%20APPROVAL_PACKAGE.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	GRISEOFULVIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
20735.2 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/065200_ORIGINAL%20APPROVAL_PACKAGE.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	GRISEOFULVIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
25.9 ng × h/mL EXPERIMENT https://link.springer.com/article/10.1007/BF00547378	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	GRISEOFULVIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
21.1 μg × h/mL EXPERIMENT https://link.springer.com/article/10.1007/BF00547378	330 mg single, oral dose: 330 mg route of administration: Oral experiment type: SINGLE co-administered:	GRISEOFULVIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
8618.89 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/050475s057lbl.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	GRISEOFULVIN unknown	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Analyte	Population
10.716 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/065200_ORIGINAL%20APPROVAL_PACKAGE.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	GRISEOFULVIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
9.043 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/065200_ORIGINAL%20APPROVAL_PACKAGE.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	GRISEOFULVIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
10.7 h EXPERIMENT https://link.springer.com/article/10.1007/BF00547378	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	GRISEOFULVIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
10.3 h EXPERIMENT https://link.springer.com/article/10.1007/BF00547378	330 mg single, oral dose: 330 mg route of administration: Oral experiment type: SINGLE co-administered:	GRISEOFULVIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
16% EXPERIMENT https://link.springer.com/article/10.1007/BF00547378	330 mg single, oral dose: 330 mg route of administration: Oral experiment type: SINGLE co-administered:		GRISEOFULVIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
		CYP1A2 701 CYP2C 15 CYP2D 1 CYP3A 129

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inducer 1573 Sources: https://doi.org/10.1080/10837450902891550 Page: 12.0	yes
CYP2C 34	inducer 1573 Sources: https://journals.sagepub.com/doi/pdf/10.1177/030006059902700402#page=7 Page: 7.0	yes
CYP2D 4	inducer 1573 Sources: https://journals.sagepub.com/doi/pdf/10.1177/030006059902700402#page=7 Page: 7.0	yes
CYP3A 298	inducer 1573 Sources: https://journals.sagepub.com/doi/pdf/10.1177/030006059902700402#page=7 Page: 7.0	yes

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-0216	http://www.3bsc.com/index/pro_info.php?id=19572
3B Scientific (Wuhan) Corp	3B1-01417	http://www.3bsc.com/index/pro_info.php?id=21629
AHH Chemical co.,ltd	API-1202	http://www.ahhchemical.com/product/API-1202.html
AK Scientific, Inc. (AKSCI)	J10209	http://www.aksci.com/item_detail.php?cat=J10209
AK Scientific, Inc. (AKSCI)	M542	http://www.aksci.com/item_detail.php?cat=M542
AbMole Bioscience	M2726	http://www.abmole.com/products/griseofulvin.html
Aceschem	ACS011873	https://www.aceschem.com/catalog/126-07-8.html
Achemtek	0104-001166	http://www.achemtek.com/126-07-8
Acorn PharmaTech	ACN-048200	http://www.acornpharmatech.com/
Acros Organics	AC227450050	https://www.fishersci.com/shop/products/griseofulvin-97-acros-organics/AC227450050
Acros Organics	AC227451000	https://www.fishersci.com/shop/products/griseofulvin-97-acros-organics/AC227451000
Alfa Aesar	B23521	https://www.alfa.com/en/catalog/B23521/
ApexBio Technology	B3680	http://www.apexbt.com/griseofulvin.html
Aurum Pharmatech LLC	NE11198	http://www.Aurumpharmatech.com/Product/ProductDetails/NE11198
AvaChem Scientific	6370	https://www.avachem.com/productSearch.asp?6370
Avantor Inc	101095-098	https://us.vwr.com/store/catalog/product.jsp?catalog_number=101095-098
BLD Pharm	BD132396	http://www.bldpharm.com/products/126-07-8.html
BioSynth	Q-201178	https://www.biosynth.com/en/products/life-science/culture-media-additives/products/Q-201178.html
CSNpharm	CSN11119	https://www.csnpharm.com/products/(+)-griseofulvin.html
Capot Chemical	17619	http://www.capotchem.com/en/17619.htm
Capot Chemical	PubChem17619	http://www.capotchem.com/en/17619.htm
Chem Scene	CS-3426	http://www.chemscene.com/126-07-8.html
Chemenu	CM110396	http://www.chemenu.com/products/CM110396
Chemspace	CSSB00000743911	https://chem-space.com/CSSB00000743911
China MainChem Co., Ltd	126-07-8	https://www.mainchem.com/product/china-griseofulvin-cas-126-07-8-supplier/
Chiralblock Biosciences	CB11571	http://www.chiralblock.com/products/126-07-8.html
Clearsynth	CS-O-30933	http://www.clearsynth.com/en/CSO30933.html
Enamine	Z1258578352	https://www.enaminestore.com/catalog/Z1258578352
Glentham Life Sciences	GA6599	http://www.glentham.com/products/product/GA6599/
LGC Standards	DRE-C14056500	https://www.lgcstandards.com/US/en/p/DRE-C14056500
LGC Standards	LGCFOR0582.00	https://www.lgcstandards.com/US/en/p/LGCFOR0582.00
LGC Standards	MM0582.00	https://www.lgcstandards.com/US/en/p/MM0582.00
Lab Network	LN00839705	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00839705
MedChem Express	HY-17583	https://www.medchemexpress.com/Griseofulvin.html
MuseChem	A000742	https://www.musechem.com/product/A000742.html
Otava	15386069	https://search.otavachemicals.com/#!/search?query=15386069&type=code&base=dbb
R&D Chemicals	8504	http://www.rdchemicals.com/chemicals.php?mode=details&mol_id=7866
Sigma-Aldrich	46309_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/46309?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	BP180_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/bp180?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	G0600000_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/g0600000?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	1299007_USP	https://www.sigmaaldrich.com/catalog/product/usp/1299007?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	1299200_USP	https://www.sigmaaldrich.com/catalog/product/usp/1299200?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S529241	http://www.smolecule.com/products/s529241
Smolecule	S752225	https://www.smolecule.com/products/s752225
TCI (Tokyo Chemical Industry)	G0384	http://www.tcichemicals.com/eshop/en/us/commodity/G0384/index.html
THE BioTek	bt-269850	https://www.thebiotek.com/product/inhibitors/bt-269850
VladaChem	VL279919-25G	https://www.vladachem.com/product.php?products=126-07-8
VladaChem	VL282011-25G	https://www.vladachem.com/product.php?products=126-07-8
abcr GmbH	AB131510	http://www.abcr.com/shop/en/AB131510
eNovation Chemicals	D544999	http://www.enovationchem.com/productDetails.asp?productID=D544999
iChemical	EBD2197944	http://www.ichemical.com/products/126-07-8.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
mcule	MCULE-1983595404	https://mcule.com/MCULE-1983595404/

PubMed

Title	Date	PubMed
[Studies in 25 patients with progressive systemic scleroderma treated by long-term administration of griseofulvin].	1973 Jun 20	4579328
[Central nervous symptoms as side effects of mycosis treatment with griseofulvin].	1974 Oct 30	4424881
Letter: Psychotic symptoms with griseofulvin.	1974 Sep 9	4408278
[A case of mixed connective tissue disease exacerbated by griseofulvin complicating aseptic meningo-encephalitis and disseminated intravascular coagulation].	1990 Oct	2084866
Effect of ursodeoxycholic acid on experimental hepatic porphyria induced by griseofulvin.	1991 Jun	1751019
Treatment of experimental pneumocystosis: review of 7 years of experience and development of a new system for classifying antimicrobial drugs.	1992 Sep	1416885
Kawasaki-like syndrome associated with griseofulvin treatment.	1993 Jul	8403486
Serial light and electron microscopic changes in renal glomeruli in mice fed griseofulvin.	1993 May-Jun	8323253
A double blind study of itraconazole vs griseofulvin in patients with tinea pedis and tinea manus.	1994 Apr 13	8145958
Proximal myopathy associated with griseofulvin therapy.	1994 Jan	7836265
An unusual case of severe griseofulvin-alcohol interaction.	1994 Jul	8010556
Hepatic injury during ketoconazole therapy in patients with onychomycosis: a controlled cohort study.	1997 Jan	8985273
Differential xenobiotic induction of CYP2A5 in mouse liver, kidney, lung, and olfactory mucosa.	1998 Aug	9698299
Cell wall active antifungal compounds produced by the marine fungus Hypoxylon oceanicum LL-15G256. III. Biological properties of 15G256 gamma.	1998 Mar	9589067
Alteration of mRNA levels of delta-aminolevulinic acid synthase, ferrochelatase and heme oxygenase-1 in griseofulvin induced protoporphyria mice.	1999 Apr	10215191
Synthesis and antimicrobial activity of 1,4-diaryl-2-azetidinones.	2000 Feb	10782387
Risk of serious skin disorders among users of oral antifungals: a population-based study.	2002 Nov 28	12456265
Formation of Mallory body-like inclusions and cell death induced by deregulated expression of keratin 18.	2002 Oct	12388748
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
[Use of topical antifungal agents].	2006 May-Jun	16989127
Antifungal property and phytochemical screening of the crude extracts of Funtumia elastica and Mallotus oppositifolius.	2006 Sep	17249309
N- and S-alpha-l-arabinopyranosyl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles. First synthesis and biological evaluation.	2007 Sep	17408811
A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine.	2008 Aug	18505790
Tinea capitis: diagnostic criteria and treatment options.	2009 Jan-Feb	19378575
Tinea capitis: diagnostic criteria and treatment options.	2009 Sep-Oct	19873694
Synthesis, in vitro antibacterial and antifungal evaluations of new alpha-hydroxyphosphonate and new alpha-acetoxyphosphonate derivatives of tetrazolo [1, 5-a] quinoline.	2010 Mar	20036039
Synthesis and the selective antifungal activity of 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine derivatives.	2010 May	20106559
Novel insights into changes in biochemical properties of keratins 8 and 18 in griseofulvin-induced toxic liver injury.	2010 Oct	20643122
Synthesis and characterization of some new quinoline based derivatives endowed with broad spectrum antimicrobial potency.	2012 Nov 15	23058887
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.	2015 May 18	25811541

Patents

Sample Use Guides

In Vivo Use Guide

Adults: Daily administration of 375 mg (as a single dose or in divided doses) will give a satisfactory response in most patients with tinea corporis, tinea cruris, and tinea capitis. For those fungal infections more difficult to eradicate, such as tinea pedis and tinea unguium, a divided dose of 750 mg is recommended. Pediatric Use: Approximately 7.3 mg per kg of body weight per day of ultramicrosize griseofulvin is an effective dose for most pediatric patients. On this basis, the following dosage schedule is suggested: 16-27 kg: 125 mg to 187.5 mg daily. over 27 kg: 187.5 mg to 375 mg daily

Route of Administration: Oral

In Vitro Use Guide

Griseofulvin displayed strong inhibitory effects on the growth of A. solani and S. aureus with MIC of 3.13 uM for each.

Name

Type

Language

GRISEOFULVIN

Official Name

English

GRISEOFULVIN [HSDB]

Common Name

English

SPIRO(BENZOFURAN-2(3H),1'-(2)CYCLOHEXENE)-3,4'-DIONE, 7-CHLORO-2',4,6-TRIMETHOXY-6'-METHYL-, (1'S-TRANS)-

Common Name

English

(1'S-TRANS)- 7-CHLORO-2',4,6-TRIMETHOXY-6'-METHYLSPIRO(BENZOFURAN-2(3H),1'-CYCLOHEX-2'-ENE)-3,4'-DIONE

Common Name

English

GRISEOFULVIN [EP MONOGRAPH]

Common Name

English

GRISEOFULVIN [MI]

Common Name

English

(1'S,6'R)-7-CHLORO-2',4,6-TRIMETHOXY-6'-METHYLSPIRO(BENZOFURAN-2(3H),1'-(2)CYCLOHEXENE)-3,4'-DIONE

Common Name

English

GRISEOFULVIN [GREEN BOOK]

Common Name

English

GRISEOFULVIN [USP-RS]

Common Name

English

GRISEOFULVIN [ORANGE BOOK]

Common Name

English

GRISACTIN V

Brand Name

English

griseofulvin [INN]

Common Name

English

GRIS-PEG

Brand Name

English

GRISEOFULVIN [IARC]

Common Name

English

7-CHLORO-2',4,6-TRIMETHOXY-6'.BETA.-METHYLSPIRO(BENZOFURAN-2(3H),1'-(2)CYCLOHEXENE)-3,4'-DIONE

Common Name

English

GRISEOFULVIN PERMEABILITY DIAMETER

Common Name

English

GRISEOFULVIN [JAN]

Common Name

English

NSC-755822

Code

English

GRISEOFULVIN PERMEABILITY DIAMETER [USP-RS]

Common Name

English

GRISEOFULVIN [USP MONOGRAPH]

Common Name

English

GRISEOFULVINUM [WHO-IP LATIN]

Common Name

English

GRISEOFULVIN [VANDF]

Common Name

English

GRISEOFULVIN [MART.]

Common Name

English

NSC-34533

Code

English

Griseofulvin [WHO-DD]

Common Name

English

GRISEOFULVIN [WHO-IP]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C514