Drug Information

Drug (ID: DG00264) and It's Reported Resistant Information

• Name: Flucytosine
• Synonyms: Alcobon; Ancobon; Ancotil; Ancotyl; Flucitosina; Flucystine; Flucytosin; Flucytosinum; Flucytosone; Fluocytosine; Fluorcytosine; Fluorocytosine; Flucitosina [DCIT]; F0321; LT00771985; Ancobon (TN); Flucytosinum [INN-Latin]; GL663142 & 5FC; Ro 2-9915; Ro 29915 E/265601; Ro-2-9915; Flucytosine (JP15/USP/INN); Flucytosine [USAN:INN:BAN:JAN]; Cytosine, 5-fluoro-(6CI,7CI,8CI); GL663142 & 4-Amino-5-fluoropyrimidin-2(1H)-one; 2(1H)-Pyrimidinone, 4-amino-5-fluoro-); 2-Hydroxy-4-amino-5-fluoropyrimidine; 4-Amino-5-fluoro-2(1H)-pyrimidinone; 4-Amino-5-fluoro-2-hydroxypyrimidine; 4-Amino-5-fluoro-2-hyroxypyrimidine; 4-Amino-5-fluoropyrimidin-2(1H)-one; 5-FC; 5-Flucytosine; 5-Fluorocystosine; 5-Fluorocytosin; 5-Fluorocytosine; 5-Fluorocytosine-6-3H; 5-Flurocytosine; 5-fluoro cytosine; 5987P; 6-Amino-2-oxo-5-fluoropyrimidine; 6-amino-5-fluoro-1H-pyrimidin-2-one; 9074P
• Indication:
  In total 1 Indication(s)
  Endocarditis [ICD-11: BB40-BA42]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Candidosis [ICD-11: 1F23]; [1]
• Target: Candida Thymidylate synthase (Candi TMP1); TYSY_CANAL; [1]
• Formula: C4H4FN3O
• IsoSMILES: C1=NC(=O)NC(=C1F)N
• InChI: 1S/C4H4FN3O/c5-2-1-7-4(9)8-3(2)6/h1H,(H3,6,7,8,9)
• InChIKey: XRECTZIEBJDKEO-UHFFFAOYSA-N
• PubChem CID: 3366
• ChEBI ID: CHEBI:5100
• TTD Drug ID: D0S5WG
• INTEDE ID: DR2287
• DrugBank ID: DB01099

Type(s) of Resistant Mechanism of This Drug

  DISM: Drug Inactivation by Structure Modification

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Candidosis [ICD-11: 1F23]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Fur1 uracil phosphoribosyltransferase (FUR1) [1]

• Molecule Alteration: Missense mutation; p.R101C
• Resistant Disease: Candida albicans infection [ICD-11: 1F23.Y]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida albicans strain; 5476
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: The epidemiological results presented here suggest that the substitution of thymine for cytosine at nucleotide position 301, resulting in a change from arginine to cysteine at amino acid position 101, is likely to be the most important mechanism of 5FC resistance found in C. albicans populations.

Key Molecule: Fur1 uracil phosphoribosyltransferase (FUR1) [2]

• Molecule Alteration: Missense mutation; p.F211I
• Resistant Disease: Candida auris infection [ICD-11: 1F23.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida auris strain; 498019
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: AFST assay
• Mechanism Description: One isolate displayed resistance to both echinocandins (micafungin, caspofungin, and anidulafungin) and 5-flucytosine; the former was associated with a serine to tyrosine amino acid substitution in the gene FkS1, and the latter was associated with a phenylalanine to isoleucine substitution in the gene FUR1.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Lanosterol 14-alpha demethylase (ERG11) [2]

• Molecule Alteration: Missense mutation; p.Y132F
• Resistant Disease: Candida auris infection [ICD-11: 1F23.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida auris strain; 498019
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: AFST assay
• Mechanism Description: One isolate displayed resistance to both echinocandins (micafungin, caspofungin, and anidulafungin) and 5-flucytosine; the former was associated with a serine to tyrosine amino acid substitution in the gene FkS1, and the latter was associated with a phenylalanine to isoleucine substitution in the gene FUR1.

References

• Ref 1: Clade-specific flucytosine resistance is due to a single nucleotide change in the FUR1 gene of Candida albicans. Antimicrob Agents Chemother. 2004 Jun;48(6):2223-7. doi: 10.1128/AAC.48.6.2223-2227.2004.
• Ref 2: Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris. Emerg Microbes Infect. 2018 Mar 29;7(1):43. doi: 10.1038/s41426-018-0045-x.