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 33 Target ID: CHEMBL2364680 Sources: http://www.drugbank.ca/drugs/DB01099	Inhibitor 8504
Thymidylate synthase 33 Target ID: CHEMBL4665 Sources: http://www.drugbank.ca/drugs/DB01099	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Candida endocarditis 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/017001s027lbl.pdf	Curative	Approved 8583	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 1971
Systemic candidiasis 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/017001s027lbl.pdf	Curative	Approved 8583	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 1971
Cryptococcal meningitis 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/017001s027lbl.pdf	Curative	Approved 8583	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 1971
Cryptococcus pulmonary infections 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/017001s027lbl.pdf	Curative	Approved 8583	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 1971
Candida urinary system infections 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/017001s027lbl.pdf	Curative	Approved 8583	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 1971

C_max

Value	Dose	Co-administered	Analyte	Population
75 μg/mL DRUG LABEL https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/5721b46a-4a9f-46c2-8804-a9bad4d5f80a/spl-doc?hl=flucytosine	37.5 mg/kg 4 times / day multiple, oral dose: 37.5 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered: AMPHOTERICIN B	AMPHOTERICIN B	FLUCYTOSINE serum	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
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: AMPHOTERICIN B	AMPHOTERICIN B	FLUCYTOSINE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
435 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: AMPHOTERICIN B	AMPHOTERICIN B	FLUCYTOSINE serum	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: AMPHOTERICIN B	AMPHOTERICIN B	FLUCYTOSINE serum	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	37.5 mg/kg 4 times / day multiple, oral dose: 37.5 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered: AMPHOTERICIN B	AMPHOTERICIN B	FLUCYTOSINE serum	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
150 mg/kg 1 times / day multiple, oral Recommended Dose: 150 mg/kg, 1 times / day Route: oral Route: multiple Dose: 150 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7803641	unhealthy, 34 Health Status: unhealthy Age Group: 34 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/7803641	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
150 mg/kg 4 times / day multiple, oral 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 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 Recommended Dose: 150 mg/kg, 1 times / day Route: oral Route: multiple Dose: 150 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7803641	unhealthy, 34 Health Status: unhealthy Age Group: 34 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/7803641
Thrombocytopenia	3.1% Disc. AE	150 mg/kg 1 times / day multiple, oral Recommended Dose: 150 mg/kg, 1 times / day Route: oral Route: multiple Dose: 150 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7803641	unhealthy, 34 Health Status: unhealthy Age Group: 34 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/7803641
Diarrhea	6.25% Disc. AE	150 mg/kg 1 times / day multiple, oral Recommended Dose: 150 mg/kg, 1 times / day Route: oral Route: multiple Dose: 150 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7803641	unhealthy, 34 Health Status: unhealthy Age Group: 34 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/7803641
Granulocytopenia	6.25% Disc. AE	150 mg/kg 1 times / day multiple, oral Recommended Dose: 150 mg/kg, 1 times / day Route: oral Route: multiple Dose: 150 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7803641	unhealthy, 34 Health Status: unhealthy Age Group: 34 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/7803641
Nausea	9.4% Disc. AE	150 mg/kg 1 times / day multiple, oral Recommended Dose: 150 mg/kg, 1 times / day Route: oral Route: multiple Dose: 150 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7803641	unhealthy, 34 Health Status: unhealthy Age Group: 34 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/7803641
Vomiting	9.4% Disc. AE	150 mg/kg 1 times / day multiple, oral Recommended Dose: 150 mg/kg, 1 times / day Route: oral Route: multiple Dose: 150 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7803641	unhealthy, 34 Health Status: unhealthy Age Group: 34 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/7803641

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
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
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

PubMed

Title	Date	PubMed
Quantitation of cytosine deaminase mRNA by real-time reverse transcription polymerase chain reaction: a sensitive method for assessing 5-fluorocytosine toxicity in vitro.	2002-02-15	11814289
Synthesis and biological activity of the new 5-fluorocytosine derivatives, 5'-deoxy-N-alkyloxycarbonyl-5-fluorocytosine-5'-carboxylic acid.	2002-02-11	11814824
Neonatal candidosis: clinical picture, management controversies and consensus, and new therapeutic options.	2002-02	11801585
The structure of Escherichia coli cytosine deaminase.	2002-01-25	11812140
Negative selection of Plasmodium falciparum reveals targeted gene deletion by double crossover recombination.	2002-01	11796125
[Infection and colonization by Scedosporium prolificans].	2001-12-19	11747789
Stereoselective synthesis of 7 alpha- and 7 beta-aminocholestanol as potent fungicidal drugs.	2001-12-03	11714599
Phenotypic characterization of Microsporum canis isolated from cats and dogs.	2001-12	11820261
Candida lusitaniae catheter-related sepsis.	2001-12	11793623
Mycetoma of the renal pelvis caused by Fusarium species.	2001-12	11740333
In vitro susceptibility of clinical isolates of Zygomycota to amphotericin B, flucytosine, itraconazole and voriconazole.	2001-12	11733480
Tumor-specific chemo-radio-gene therapy for colorectal cancer cells using adenovirus vector expressing the cytosine deaminase gene.	2001-11-29	11724328
Transduction of thymidine phosphorylase cDNA facilitates efficacy of cytosine deaminase/5-FC gene therapy for malignant brain tumor.	2001-11-29	11724281
Development of azole resistance during fluconazole maintenance therapy for AIDS-associated cryptococcal disease.	2001-11-23	11698718
Enantiomeric synthesis of D- and L-cyclopentenyl nucleosides and their antiviral activity against HIV and West Nile virus.	2001-11-08	11689085
Pharmacotherapy of fungal eye infections.	2001-11	11825321
The echinocandins, first novel class of antifungals in two decades: will they live up to their promise?	2001-11	11770362
Case report. Mycotic arteritis due to Aspergillus fumigatus in a diabetic with retrobulbar aspergillosis and mycotic meningitis.	2001-11	11766108
Evaluation of amphotericin B and flucytosine in combination against Candida albicans and Cryptococcus neoformans using time-kill methodology.	2001-11	11750164
Cytometric approach for a rapid evaluation of susceptibility of Candida strains to antifungals.	2001-11	11737085
Crystallization and preliminary X-ray analysis of bacterial cytosine deaminase.	2001-11	11679731
Effect of the growth medium on the in vitro antifungal activity of micafungin (FK-463) against clinical isolates of Candida dubliniensis.	2001-11	11679561
Sertaconazole: in-vitro antifungal activity against vaginal and other superficial yeast isolates.	2001-10	11760221
Cryptococcus neoformans infection in a cohort of Italian AIDS patients: natural history, early prognostic parameters, and autopsy findings.	2001-10	11757972
In vivo gene therapy for colon cancer using adenovirus-mediated, transfer of the fusion gene cytosine deaminase and uracil phosphoribosyltransferase.	2001-10	11704815
[Combined gene therapy for murine liver cancer with interleukin-18 and cytosine deaminase genes].	2001-10	11676879
Development of Saccharomyces cerevisiae as a model pathogen. A system for the genetic identification of gene products required for survival in the mammalian host environment.	2001-10	11606528
Evaluation of the acute and subchronic toxic effects in mice, rats, and monkeys of the genetically engineered and Escherichia coli cytosine deaminase gene-incorporated Salmonella strain, TAPET-CD, being developed as an antitumor agent.	2001-09-21	11563416
Synthesis and antiproliferative activity of some 4'-C-hydroxymethyl-alpha- and -beta-D-arabino-pentofuranosyl pyrimidine nucleosides.	2001-09-21	11563083
Adenovirus gene transfer vectors inhibit growth of lymphatic tumor metastases independent of a therapeutic transgene.	2001-09-01	11535167
Sensitization of prostate cancer cell lines to 5-fluorocytosine induced by adenoviral vector carrying a CD transcription unit.	2001-09	11780394
Successful treatment of cryptococcal osteomyelitis and paraspinous abscess with fluconazole and flucytosine.	2001-09	11592758
Post-antifungal effect of polyene, azole and DNA-analogue agents against oral Candida albicans and Candida tropicalis isolates in HIV disease.	2001-09	11545239
Carcinoembryonic antigen-specific suicide gene therapy of cytosine deaminase/5-fluorocytosine enhanced by the cre/loxP system in the orthotopic gastric carcinoma model.	2001-08-15	11507067
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.	2001-08-10	11529249
Treatment of acute cryptococcal disease.	2001-08	11584993
Hepatic intra-arterial delivery of a retroviral vector expressing the cytosine deaminase gene, controlled by the CEA promoter and intraperitoneal treatment with 5-fluorocytosine suppresses growth of colorectal liver metastases.	2001-08	11509957
In vivo suicide gene therapy model using a newly discovered prostate-specific membrane antigen promoter/enhancer: a potential alternative approach to androgen deprivation therapy.	2001-08	11502468
In vitro antifungal susceptibility testing.	2001-08	11501985
Discontinuation of secondary prophylaxis against cryptococcosis in patients with AIDS receiving highly active antiretroviral therapy.	2001-07-27	11504971
Systemic antifungal agents.	2001-07	11519290
[A case of SLE presenting the features of antiphospholipid antibody syndrome during a treatment for complicated cryptococcal meningitis].	2001-07	11517489
In vitro susceptibility pattern of Sporothrix schenckii strains isolated from three centers in India.	2001-06	11816955
[In vitro antifungal susceptibility of dematiaceous filamentous fungi using the E-test].	2001-06	11704774
A rapid assay for mitochondrial DNA damage and respiratory chain inhibition in the yeast Saccharomyces cerevisiae.	2001	11746749
Update on HER-2 as a target for cancer therapy: the ERBB2 promoter and its exploitation for cancer treatment.	2001	11737892
[Mycosis in kidney transplant patients].	2001	11704745
Hypoxia and oxidative stress. Tumour hypoxia--therapeutic considerations.	2001	11597323
The therapeutic monitoring of antimicrobial agents.	2001	11564051
Gene therapy for colorectal cancer: therapeutic potential.	2001	11520247

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 `Mon Mar 31 17:36:33 GMT 2025` Edited by `admin` on `Mon Mar 31 17:36:33 GMT 2025`
Record UNII	D83282DT06
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

5-Fluorocytosine

Preferred Name

English

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

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