FLUCYTOSINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C4H4FN3O
Molecular Weight	129.0925
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC(=O)NC=C1F

InChI

InChIKey=XRECTZIEBJDKEO-UHFFFAOYSA-N

InChI=1S/C4H4FN3O/c5-2-1-7-4(9)8-3(2)6/h1H,(H3,6,7,8,9)

HIDE SMILES / InChI

Molecular Formula	C4H4FN3O
Molecular Weight	129.0925
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/017001s027lbl.pdf
Curator's Comment: Description was created using several sources including: http://www.uptodate.com/contents/pharmacology-of-flucytosine-5-fc; http://www.ncbi.nlm.nih.gov/pubmed/6338821; http://www.ncbi.nlm.nih.gov/pubmed/10933638

Flucytosine (5-flucytosine, Ancobon) is an antifungal agent used for treatment of serious fungal infections caused by Candida or Cryptococcus. A fluorinated cytosine analog it was originally developed as an anti-tumor agent, but was found to be non-effective against tumors. Monotherapy with 5-FC is limited because of the frequent development of pathogens resistance. It is often used in in combination with amphotericin B. The severe side effects of 5-flucytosine include hepatotoxicity and bone-marrow depression. 5-fluorocytosine is a prodrug to the cytotoxic compound 5-fluorouracil. Although the exact mode of action is unknown, it has been proposed that flucytosine acts directly on fungal organisms by competitive inhibition of purine and pyrimidine uptake and indirectly by intracellular metabolism to 5-fluorouracil. Flucytosine is taken up by fungal organisms via the enzyme cytosine permease. Inside the fungal cell, flucytosine is rapidly converted to fluorouracil by the enzyme cytosine deaminase. Fluorouracil exerts its antifungal activity through the subsequent conversion into several active metabolites, which inhibit protein synthesis by being falsely incorporated into fungal RNA or interfere with the biosynthesis of fungal DNA through the inhibition of the enzyme thymidylate synthetase.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Thymidylate synthase 31 Target ID: CHEMBL2364680 Sources: http://www.drugbank.ca/drugs/DB01099	Inhibitor 8228
Thymidylate synthase 31 Target ID: CHEMBL4665 Sources: http://www.drugbank.ca/drugs/DB01099	Inhibitor 8228

Conditions

Condition	Modality	Highest Phase	Product
Candida endocarditis 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/017001s027lbl.pdf	Curative	Approved 8360	ANCOBON Approved Use INDICATIONS & USAGE Flucytosine Capsules is indicated only in the treatment of serious infections caused by susceptible strains of Candida and/or Cryptococcus. Candida: Septicemia, endocarditis and urinary system infections have been effectively treated with flucytosine. Limited trials in pulmonary infections justify the use of flucytosine. Cryptococcus: Meningitis and pulmonary infections have been treated effectively. Studies in septicemias and urinary tract infections are limited, but good responses have been reported. Flucytosine Capsules should be used in combination with amphotericin B for the treatment of systemic candidiasis and cryptococcosis because of the emergence of resistance to Flucytosine Capsules (see MICROBIOLOGY). Launch Date 5.9961598E10
Systemic candidiasis 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/017001s027lbl.pdf	Curative	Approved 8360	ANCOBON Approved Use INDICATIONS & USAGE Flucytosine Capsules is indicated only in the treatment of serious infections caused by susceptible strains of Candida and/or Cryptococcus. Candida: Septicemia, endocarditis and urinary system infections have been effectively treated with flucytosine. Limited trials in pulmonary infections justify the use of flucytosine. Cryptococcus: Meningitis and pulmonary infections have been treated effectively. Studies in septicemias and urinary tract infections are limited, but good responses have been reported. Flucytosine Capsules should be used in combination with amphotericin B for the treatment of systemic candidiasis and cryptococcosis because of the emergence of resistance to Flucytosine Capsules (see MICROBIOLOGY). Launch Date 5.9961598E10
Cryptococcal meningitis 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/017001s027lbl.pdf	Curative	Approved 8360	ANCOBON Approved Use INDICATIONS & USAGE Flucytosine Capsules is indicated only in the treatment of serious infections caused by susceptible strains of Candida and/or Cryptococcus. Candida: Septicemia, endocarditis and urinary system infections have been effectively treated with flucytosine. Limited trials in pulmonary infections justify the use of flucytosine. Cryptococcus: Meningitis and pulmonary infections have been treated effectively. Studies in septicemias and urinary tract infections are limited, but good responses have been reported. Flucytosine Capsules should be used in combination with amphotericin B for the treatment of systemic candidiasis and cryptococcosis because of the emergence of resistance to Flucytosine Capsules (see MICROBIOLOGY). Launch Date 5.9961598E10
Cryptococcus pulmonary infections 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/017001s027lbl.pdf	Curative	Approved 8360	ANCOBON Approved Use INDICATIONS & USAGE Flucytosine Capsules is indicated only in the treatment of serious infections caused by susceptible strains of Candida and/or Cryptococcus. Candida: Septicemia, endocarditis and urinary system infections have been effectively treated with flucytosine. Limited trials in pulmonary infections justify the use of flucytosine. Cryptococcus: Meningitis and pulmonary infections have been treated effectively. Studies in septicemias and urinary tract infections are limited, but good responses have been reported. Flucytosine Capsules should be used in combination with amphotericin B for the treatment of systemic candidiasis and cryptococcosis because of the emergence of resistance to Flucytosine Capsules (see MICROBIOLOGY). Launch Date 5.9961598E10
Candida urinary system infections 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/017001s027lbl.pdf	Curative	Approved 8360	ANCOBON Approved Use INDICATIONS & USAGE Flucytosine Capsules is indicated only in the treatment of serious infections caused by susceptible strains of Candida and/or Cryptococcus. Candida: Septicemia, endocarditis and urinary system infections have been effectively treated with flucytosine. Limited trials in pulmonary infections justify the use of flucytosine. Cryptococcus: Meningitis and pulmonary infections have been treated effectively. Studies in septicemias and urinary tract infections are limited, but good responses have been reported. Flucytosine Capsules should be used in combination with amphotericin B for the treatment of systemic candidiasis and cryptococcosis because of the emergence of resistance to Flucytosine Capsules (see MICROBIOLOGY). Launch Date 5.9961598E10

C_max

Value	Dose	Co-administered	Analyte	Population
57.3 mg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20038612	1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUCYTOSINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
506 mg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20038612	1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUCYTOSINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.11 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20038612	1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUCYTOSINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
96.6% DRUG LABEL https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/5721b46a-4a9f-46c2-8804-a9bad4d5f80a/spl-doc?hl=flucytosine			FLUCYTOSINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
150 mg/kg 1 times / day multiple, oral (total daily dose) Recommended Dose: 150 mg/kg, 1 times / day Route: oral Route: multiple Dose: 150 mg/kg, 1 times / day Co-administed with:: fluconazole, p.o(400 mg/d) Sources: https://pubmed.ncbi.nlm.nih.gov/7803641 Page: p.743	unhealthy, 34 n = 32 Health Status: unhealthy Condition: Cryptococcal meningitis Age Group: 34 Sex: M Population Size: 32 Sources: https://pubmed.ncbi.nlm.nih.gov/7803641 Page: p.743	Disc. AE: Vomiting, Nausea... AEs leading to discontinuation/dose reduction: Vomiting (9.4%) Nausea (9.4%) Diarrhea (6.25%) Granulocytopenia (6.25%) Thrombocytopenia (3.1%) Rash (3.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/7803641 Page: p.743
150 mg/kg 4 times / day multiple, oral (total daily dose\|max) Recommended Dose: 150 mg/kg, 4 times / day Route: oral Route: multiple Dose: 150 mg/kg, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/017001s027lbl.pdf	unhealthy Health Status: unhealthy Condition: Infections caused by susceptible strains of Candida and/or Cryptococcus Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/017001s027lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/017001s027lbl.pdf

AEs

AE	Significance	Dose	Population
Rash	3.1% Disc. AE	150 mg/kg 1 times / day multiple, oral (total daily dose) Recommended Dose: 150 mg/kg, 1 times / day Route: oral Route: multiple Dose: 150 mg/kg, 1 times / day Co-administed with:: fluconazole, p.o(400 mg/d) Sources: https://pubmed.ncbi.nlm.nih.gov/7803641 Page: p.743	unhealthy, 34 n = 32 Health Status: unhealthy Condition: Cryptococcal meningitis Age Group: 34 Sex: M Population Size: 32 Sources: https://pubmed.ncbi.nlm.nih.gov/7803641 Page: p.743
Thrombocytopenia	3.1% Disc. AE	150 mg/kg 1 times / day multiple, oral (total daily dose) Recommended Dose: 150 mg/kg, 1 times / day Route: oral Route: multiple Dose: 150 mg/kg, 1 times / day Co-administed with:: fluconazole, p.o(400 mg/d) Sources: https://pubmed.ncbi.nlm.nih.gov/7803641 Page: p.743	unhealthy, 34 n = 32 Health Status: unhealthy Condition: Cryptococcal meningitis Age Group: 34 Sex: M Population Size: 32 Sources: https://pubmed.ncbi.nlm.nih.gov/7803641 Page: p.743
Diarrhea	6.25% Disc. AE	150 mg/kg 1 times / day multiple, oral (total daily dose) Recommended Dose: 150 mg/kg, 1 times / day Route: oral Route: multiple Dose: 150 mg/kg, 1 times / day Co-administed with:: fluconazole, p.o(400 mg/d) Sources: https://pubmed.ncbi.nlm.nih.gov/7803641 Page: p.743	unhealthy, 34 n = 32 Health Status: unhealthy Condition: Cryptococcal meningitis Age Group: 34 Sex: M Population Size: 32 Sources: https://pubmed.ncbi.nlm.nih.gov/7803641 Page: p.743
Granulocytopenia	6.25% Disc. AE	150 mg/kg 1 times / day multiple, oral (total daily dose) Recommended Dose: 150 mg/kg, 1 times / day Route: oral Route: multiple Dose: 150 mg/kg, 1 times / day Co-administed with:: fluconazole, p.o(400 mg/d) Sources: https://pubmed.ncbi.nlm.nih.gov/7803641 Page: p.743	unhealthy, 34 n = 32 Health Status: unhealthy Condition: Cryptococcal meningitis Age Group: 34 Sex: M Population Size: 32 Sources: https://pubmed.ncbi.nlm.nih.gov/7803641 Page: p.743
Nausea	9.4% Disc. AE	150 mg/kg 1 times / day multiple, oral (total daily dose) Recommended Dose: 150 mg/kg, 1 times / day Route: oral Route: multiple Dose: 150 mg/kg, 1 times / day Co-administed with:: fluconazole, p.o(400 mg/d) Sources: https://pubmed.ncbi.nlm.nih.gov/7803641 Page: p.743	unhealthy, 34 n = 32 Health Status: unhealthy Condition: Cryptococcal meningitis Age Group: 34 Sex: M Population Size: 32 Sources: https://pubmed.ncbi.nlm.nih.gov/7803641 Page: p.743
Vomiting	9.4% Disc. AE	150 mg/kg 1 times / day multiple, oral (total daily dose) Recommended Dose: 150 mg/kg, 1 times / day Route: oral Route: multiple Dose: 150 mg/kg, 1 times / day Co-administed with:: fluconazole, p.o(400 mg/d) Sources: https://pubmed.ncbi.nlm.nih.gov/7803641 Page: p.743	unhealthy, 34 n = 32 Health Status: unhealthy Condition: Cryptococcal meningitis Age Group: 34 Sex: M Population Size: 32 Sources: https://pubmed.ncbi.nlm.nih.gov/7803641 Page: p.743

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5100	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5100
ChemicalBook	CB6744939	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6744939
MolPort	MolPort-000-155-561	https://www.molport.com/shop/molecule-link/MolPort-000-155-561
MolPort	MolPort-001-774-493	https://www.molport.com/shop/molecule-link/MolPort-001-774-493
MolPort	MolPort-002-317-353	https://www.molport.com/shop/molecule-link/MolPort-002-317-353
Selleck Chemicals	Flucytosine(Ancobon)	http://www.selleckchem.com/products/Flucytosine(Ancobon).html
ZINC	ZINC000000896546	http://zinc15.docking.org/substances/ZINC000000896546
eMolecules	511893	https://www.emolecules.com/cgi-bin/more?vid=511893
eMolecules	538448	https://www.emolecules.com/cgi-bin/more?vid=538448
eMolecules	736052	https://www.emolecules.com/cgi-bin/more?vid=736052
eMolecules	914155	https://www.emolecules.com/cgi-bin/more?vid=914155

PubMed

Title	Date	PubMed
Combined activity of amphotericin B and 5-fluorocytosine against Cryptococcus neoformans in vitro and in vivo in mice.	1975 Feb	1090685
Synergistic effects of low doses of histatin 5 and its analogues on amphotericin B anti-mycotic activity.	2000 Aug	11204768
Comparison of the Etest and microdilution method for antifungal susceptibility testing of Cryptococcus neoformans to four antifungal agents.	2000 Dec	11102421
Synthesis and antifungal activities of 5/6-arylamino-4,7-dioxobenzothiazoles.	2000 Jul 17	10915058
Activity of voriconazole against Candida albicans and Candida krusei isolated since 1984.	2000 Nov	11091037
In vitro antifungal activity of a novel lipopeptide antifungal agent, FK463, against various fungal pathogens.	2000 Oct	11132964
Potent synergism of the combination of fluconazole and cyclosporine in Candida albicans.	2000 Sep	10952582
[Mycosis in kidney transplant patients].	2001	11704745
Electrophoretic karyotyping and antifungal susceptibility patterns of Candida parapsilosis clinical isolates causing deep and superficial fungal infections.	2001	11307593
Specific targeting of cytosine deaminase to solid tumors by engineered Clostridium acetobutylicum.	2001 Apr	11393282
Hydrophilic interaction chromatography using amino and silica columns for the determination of polar pharmaceuticals and impurities.	2001 Apr 13	11355803
Synthesis and antiproliferative activity of some 4'-C-hydroxymethyl-alpha- and -beta-D-arabino-pentofuranosyl pyrimidine nucleosides.	2001 Apr-Jul	11563083
In vivo suicide gene therapy model using a newly discovered prostate-specific membrane antigen promoter/enhancer: a potential alternative approach to androgen deprivation therapy.	2001 Aug	11502468
In vitro antifungal susceptibility testing.	2001 Aug	11501985
A phase I trial of genetically modified Salmonella typhimurium expressing cytosine deaminase (TAPET-CD, VNP20029) administered by intratumoral injection in combination with 5-fluorocytosine for patients with advanced or metastatic cancer. Protocol no: CL-017. Version: April 9, 2001.	2001 Aug 10	11529249
Candida lusitaniae catheter-related sepsis.	2001 Dec	11793623
Stereoselective synthesis of 7 alpha- and 7 beta-aminocholestanol as potent fungicidal drugs.	2001 Dec 3	11714599
Phaeohyphomycosis due to Cladosporium cladosporioides.	2001 Feb	11270401
In vitro activity of a new echinocandin, LY303366, and comparison with fluconazole, flucytosine and amphotericin B against Candida species.	2001 Jan	11284937
Usefulness of repeated direct intratumoral gene transfer using hemagglutinating virus of Japan-liposome method for cytosine deaminase suicide gene therapy.	2001 Jan 1	11196152
Suicide gene therapy on LNCaP human prostate cancer cells.	2001 Jul	11442669
Transduction of thymidine phosphorylase cDNA facilitates efficacy of cytosine deaminase/5-FC gene therapy for malignant brain tumor.	2001 Jul-Aug	11724281
In vitro susceptibility pattern of Sporothrix schenckii strains isolated from three centers in India.	2001 Jun	11816955
[In vitro antifungal susceptibility of dematiaceous filamentous fungi using the E-test].	2001 Jun	11704774
[The activity of systemic antimycotic drug combinations].	2001 Mar	11376347
Increasing specificity of anti-tumor therapy: cytotoxic protein delivery by non-pathogenic clostridia under regulation of radio-induced promoters.	2001 Mar-Apr	11396175
Therapy for fungal infections in leukemia.	2001 May	11296129
Pharmacotherapy of fungal eye infections.	2001 Nov	11825321
The echinocandins, first novel class of antifungals in two decades: will they live up to their promise?	2001 Nov	11770362
Crystallization and preliminary X-ray analysis of bacterial cytosine deaminase.	2001 Nov	11679731
Sertaconazole: in-vitro antifungal activity against vaginal and other superficial yeast isolates.	2001 Oct	11760221
In vivo gene therapy for colon cancer using adenovirus-mediated, transfer of the fusion gene cytosine deaminase and uracil phosphoribosyltransferase.	2001 Oct	11704815
Sensitization of prostate cancer cell lines to 5-fluorocytosine induced by adenoviral vector carrying a CD transcription unit.	2001 Sep	11780394
Neonatal candidosis: clinical picture, management controversies and consensus, and new therapeutic options.	2002 Feb	11801585
Negative selection of Plasmodium falciparum reveals targeted gene deletion by double crossover recombination.	2002 Jan	11796125

Patents

Sample Use Guides

In Vivo Use Guide

The usual dosage is 50 to 150 mg/kg/day administered in divided doses at 6- hour intervals.

Route of Administration: Oral

In Vitro Use Guide

MIC ≤4 ug/ml for susceptible pathogen

Substance Class	Chemical Created by `admin` on `Wed Jul 05 22:34:51 UTC 2023` Edited by `admin` on `Wed Jul 05 22:34:51 UTC 2023`
Record UNII	D83282DT06
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FLUCYTOSINE

Official Name

English

5-FLUOROCYTOSINE [WHO-IP]

Common Name

English

RO-29915

Code

English

RO 2-9915

Code

English

ANCOBON

Brand Name

English

FLUCYTOSINE [WHO-IP]

Common Name

English

5-Fluorocytosine

Systematic Name

English

FLUCYTOSINE [USP IMPURITY]

Common Name

English

FLUOROCYTOSINE

Systematic Name

English

FLUCYTOSINE [MI]

Common Name

English

NSC-103805

Code

English

RO-2-9915

Code

English

FLUCYTOSINE [HSDB]

Common Name

English

FLUCYTOSINE [USAN]

Common Name

English

Flucytosine [WHO-DD]

Common Name

English

FLUCYTOSINE [ORANGE BOOK]

Common Name

English

CYTOSINE, 5-FLUORO-

Systematic Name

English

4-AMINO-5-FLUOROPYRIMIDIN-2(1H)-ONE [WHO-IP]

Systematic Name

English

FLUCYTOSINE [EP MONOGRAPH]

Common Name

English

FLUCYTOSINE [MART.]

Common Name

English

FLUCYTOSINE [USP-RS]

Common Name

English

FLUCYTOSINE [USP MONOGRAPH]

Common Name

English

FLUCYTOSINE [JAN]

Common Name

English

EMTRICITABINE IMPURITY E [WHO-IP]

Common Name

English

FLUCYTOSINUM [WHO-IP LATIN]

Common Name

English

flucytosine [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1557