Banner
targets (3)
for drugs
Identification
Name Flucytosine
Accession Number DB01099 (APRD00299)
Type small molecule
Groups approved
Description

A fluorinated cytosine analog that is used as an antifungal agent. [PubChem]

Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
5-FC
5-Fluorocystosine
5-Fluorocytosin
5-Fluorocytosine
5-Flurocytosine
Flucytosin
Fluocytosine
Fluorcytosine
Salts Not Available
Brand names
Name Company
Ancobon
Ancotil
Brand mixtures Not Available
Categories
  • Antimetabolites
  • Antifungals
  • Antifungal Agents
CAS number 2022-85-7
Weight Average: 129.0925
Monoisotopic: 129.03383997
Chemical Formula C4H4FN3O
InChI Key InChIKey=XRECTZIEBJDKEO-UHFFFAOYSA-N
InChI
InChI=1S/C4H4FN3O/c5-2-1-7-4(9)8-3(2)6/h1H,(H3,6,7,8,9)
Plain Text
IUPAC Name
6-amino-5-fluoro-1,2-dihydropyrimidin-2-one
SMILES
NC1=C(F)C=NC(=O)N1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Pyrimidines and Derivatives
Substructures
  • Aliphatic and Aryl Amines
  • Pyrimidines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Cyanamides
  • Aryl Halides
Pharmacology
Indication For the treatment (in combination with amphotericin B) of serious infections caused by susceptible strains of Candida (septicemia, endocarditis and urinary system infections) and/or Cryptococcus (meningitis and pulmonary infections).
Pharmacodynamics Flucytosine is an antimetabolite that acts as an antifungal agent with in vitro and in vivo activity against Candida and Cryptococcus. Flucytosine enters the fungal cell via cytosine permease; thus, flucytosine is metabolized to 5-fluorouracil within fungal organisms. The 5-fluorouracil is extensively incorporated into fungal RNA and inhibits synthesis of both DNA and RNA. The result is unbalanced growth and death of the fungal organism. Antifungal synergism between Ancobon and polyene antibiotics, particularly amphotericin B, has been reported.
Mechanism of action 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 enters the fungal cell via cytosine permease; thus, flucytosine is metabolized to 5-fluorouracil within fungal organisms. The 5-fluorouracil is extensively incorporated into fungal RNA and inhibits synthesis of both DNA and RNA. The result is unbalanced growth and death of the fungal organism. It also appears to be an inhibitor of fungal thymidylate synthase.
Absorption Rapidly and virtually completely absorbed following oral administration. Bioavailability 78% to 89%.
Volume of distribution Not Available
Protein binding 28-31%
Metabolism Flucytosine is deaminated, possibly by gut bacteria or by the fungal targets, to 5-fluorouracil, the active metabolite.
Route of elimination Flucytosine is excreted via the kidneys by means of glomerular filtration without significant tubular reabsorption. A small portion of the dose is excreted in the feces.
Half life 2.4 to 4.8 hours.
Clearance Not Available
Toxicity Oral, rat: LD50 = >15 gm/kg.
Affected organisms
  • Yeast and other fungi
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Valeant pharmaceuticals international
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Solution Intravenous
Prices
Unit description Cost Unit
Ancobon 500 mg capsule 45.54 USD capsule
Ancobon 250 mg capsule 23.09 USD capsule
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 296 °C PhysProp
water solubility 1.5E+004 mg/L (at 25 °C) MERCK INDEX (1996)
logP -1.1 Not Available
pKa 3.26 BUDAVARI,S ET AL. (1996)
Predicted Properties
Property Value Source
water solubility 1.92e+00 g/l ALOGPS
logP -0.24 ALOGPS
logP -0.95 ChemAxon
logS -1.8 ALOGPS
pKa (strongest acidic) 8.16 ChemAxon
pKa (strongest basic) 1.06 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 67.48 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 38.22 ChemAxon
polarizability 9.97 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00323 Link_out
PubChem Compound 3366 Link_out
PubChem Substance 46504735 Link_out
ChemSpider 3249 Link_out
BindingDB 50241247 Link_out
ChEBI 5100 Link_out
ChEMBL 5100 Link_out
Therapeutic Targets Database DAP001542 Link_out
PharmGKB PA449654 Link_out
RxList http://www.rxlist.com/cgi/generic3/flucytosine.htm Link_out
Drugs.com http://www.drugs.com/cdi/flucytosine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Flucytosine Link_out
ATC Codes
  • D01AE21
  • J02AX01
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (128 KB)
MSDS show (57.3 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. DNA

Pharmacological action: yes
Actions: cross-linking/alkylation

DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

Gene Sequence: FASTA

References:
  1. Osterman DG, DePillis GD, Wu JC, Matsuda A, Santi DV: 5-Fluorocytosine in DNA is a mechanism-based inhibitor of HhaI methylase. Biochemistry. 1988 Jul 12;27(14):5204-10. Pubmed
  2. Waldorf AR, Polak A: Mechanisms of action of 5-fluorocytosine. Antimicrob Agents Chemother. 1983 Jan;23(1):79-85. Pubmed
  3. Wyszynski MW, Gabbara S, Kubareva EA, Romanova EA, Oretskaya TS, Gromova ES, Shabarova ZA, Bhagwat AS: The cysteine conserved among DNA cytosine methylases is required for methyl transfer, but not for specific DNA binding. Nucleic Acids Res. 1993 Jan 25;21(2):295-301. Pubmed

2. DNA (cytosine-5)-methyltransferase 1

Pharmacological action: unknown
Actions: other

Methylates CpG residues. Preferentially methylates hemimethylated DNA. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2

Organism class: human
UniProt ID: P26358 Link_out
Gene: DNMT1 Link_out
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. Shieh FK, Reich NO: AdoMet-dependent Methyl-transfer: Glu(119) Is Essential for DNA C5-Cytosine Methyltransferase M.HhaI. J Mol Biol. 2007 Aug 19;. Pubmed
  4. Wyszynski MW, Gabbara S, Kubareva EA, Romanova EA, Oretskaya TS, Gromova ES, Shabarova ZA, Bhagwat AS: The cysteine conserved among DNA cytosine methylases is required for methyl transfer, but not for specific DNA binding. Nucleic Acids Res. 1993 Jan 25;21(2):295-301. Pubmed

3. Thymidylate synthase

Pharmacological action: unknown
Actions: inhibitor
Organism class: fungal
UniProt ID: P12461 Link_out
Gene: TMP1
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. Fox BA, Belperron AA, Bzik DJ: Stable transformation of Toxoplasma gondii based on a pyrimethamine resistant trifunctional dihydrofolate reductase-cytosine deaminase-thymidylate synthase gene that confers sensitivity to 5-fluorocytosine. Mol Biochem Parasitol. 1999 Jan 5;98(1):93-103. Pubmed
  4. Rehemtulla A, Hamstra DA, Kievit E, Davis MA, Ng EY, Dornfeld K, Lawrence TS: Extracellular expression of cytosine deaminase results in increased 5-FU production for enhanced enzyme/prodrug therapy. Anticancer Res. 2004 May-Jun;24(3a):1393-9. Pubmed
  5. Wang ZH, Samuels S, Gama Sosa MA, Kolodny EH: 5-Fluorocytosine-mediated apoptosis and DNA damage in glioma cells engineered to express cytosine deaminase and their enhancement with interferon. J Neurooncol. 1998 Feb;36(3):219-29. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19