Pyrazofurin

Pyrazofurin, a pyrimidine nucleoside analogue with antineoplastic activity, inhibits cell proliferation and DNA synthesis in cells by inhibiting uridine 5'-phosphate (UMP) synthase[1]. Pyrazofurin is an active, sensitive orotate-phosphoribosyltransferase inhibitor with IC50s between 0.06-0.37 µM in the three squamous cell carcinoma (SCC) cell lines Hep-2, HNSCC-14B and HNSCC-14C[2].

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

[1]. Ringer DP, et al. Alteration in de novo pyrimidine biosynthesis during uridine reversal of pyrazofurin-inhibited DNA synthesis. Neuropsychopharmacology. J Biochem Toxicol. 1991 Spring;6(1):19-27.

[2]. Peters GJ, et al. Antipyrimidine effects of five different pyrimidine de novo synthesis inhibitors in three head and neck cancer cell lines. Nucleosides Nucleotides Nucleic Acids. 2018;37(6):329-339.

MOLECULAR FORMULA :

C9-H13-N3-O6

MOLECULAR WEIGHT :

259.25

WISWESSER LINE NOTATION :

T5OTJ B1Q CQ DQ E- CT5MNJ DQ EVZ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human

DOSE/DURATION :

108 mg/kg/5D

TOXIC EFFECTS :

Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting Skin and Appendages - dermatitis, other (after systemic exposure)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human

DOSE/DURATION :

48 mg/kg/5D

TOXIC EFFECTS :

Gastrointestinal - other changes Blood - changes in bone marrow (not otherwise specified)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human

DOSE/DURATION :

84 mg/kg/5D

TOXIC EFFECTS :

Blood - changes in bone marrow (not otherwise specified) Skin and Appendages - dermatitis, other (after systemic exposure)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human

DOSE/DURATION :

108 mg/kg/5D

TOXIC EFFECTS :

Gastrointestinal - other changes Blood - changes in bone marrow (not otherwise specified)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human

DOSE/DURATION :

144 mg/kg/5D

TOXIC EFFECTS :

Gastrointestinal - other changes Blood - changes in bone marrow (not otherwise specified) Skin and Appendages - dermatitis, other (after systemic exposure)

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

70 mg/kg

TOXIC EFFECTS :

Behavioral - food intake (animal) Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - dehydration

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

10 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - body temperature decrease

MUTATION DATA

TYPE OF TEST :

DNA inhibition

TEST SYSTEM :

Rodent - guinea pig Lymphocyte

DOSE/DURATION :

10 umol/L

REFERENCE :

JBTOEB Journal of Biochemical Toxicology. (VCH Publishers, Inc., 220 E. 23rd St., Suite 909, New York, NY USA 10010) V.1- 1986- Volume(issue)/page/year: 6,19,1991