6-Azauridine

log Kow = -2.14

-2.14

Soluble in water

36.2 [ug/mL] (The mean of the results at pH 7.4)

pKa = 6.63

pKa: 6.7 /Triacetyl deriv/

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P261, P264, P270, P271, P280, P301+P317, P302+P352, P304+P340, P317, P318, P321, P330, P362+P364, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 39 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Sixteen unselected patients with non-resectable hepatocellular carcinoma were treated in a phase I study with 261 cycles of D-galactosamine and 6-azauridine prior to 5-fluorouridine. Thirty % of the patients survived for more than 1 yr without signs of tumor progression and with an unchanged performance status. The compatibility of this chemotherapeutical method was quite satisfactory. The only extrahepatic side effect was a leukcopenia and/or thrombocytopenia which was reversible upon reduction of the 5-fluorouridine dose. The heterogeneity of the 16 patients treated to date does not allow a definite statistical evaluation of the reported clinical observations and results.

The effect of pyridoxine on 6-azauridine triacetate (6-AzUrd-TA) induced hyper beta-alaninemia was studied in New Zealand albino rabbits in three experiments. In each of the three experiments the animals were admin by gavage: Group 1 (Control), drinking water; Group 2, 6-AzUrd-TA; and Group 3, 6-AzUrd-TA with pyridoxine. While no beta-alanine was found in the control group or in pretreatment samples of the 6-AzUrd-Ta and 6-AzUrd-TA plus pyridoxine treated animals, high concn of this amino acid (191.0 + or - 91.6, 220.2 + or - 116.3, 103.2 + or - 64.4 nmol/ml) were found on the fourth and seventh days of 6-AzUrd-TA treatment with daily doses of 1.0 g/kg and 0.5 g/kg body weight, respectively. The drug induced hyper beta-alaninemia was significantly (p < or = 0.05) reduced in all three experiments by simultaneous pyridoxine admin in daily doses of 50 mg/kg body weight. These results indicate that daily repeated oral admin of 6-AzUrd-Ta causes elevation of serum beta-alanine, which can be partially prevented by oral admin of pyridoxine. They also indirectly support the hypothesis that 6-AzUrd-TA induced hyper beta-alaninemia is at least partially caused by the inhibition of beta-alanine degrading enzymes, that use pyridoxal phosphate as a coenzyme. /6-Azauridine triacetate/

Twenty-five metabolites (purines, pyrimidines, nucleosides and nucleosides) were tested for their simultaneous action with 6-azauridine (AzUrd) in inhibition of Newcastle disease virus (NDV) replication. With the exception of deoxyadenosine and cyclic AMP all natural adenine derivatives exerted a synergic effect with AzUrd like ATP. Glutamine in combination with AzUrd did not inhibit NDV replication. The inhibitory effect of the combination of AzUrd and adenine derivatives was reversible by guanosine, uridine and cytidine but not by orotic acid or orotidylic acid.

/SIGNS AND SYMPTOMS/ Moderate anemia, characterized by mild megaloblastic changes, reticulocytopenia, and elevated plasma iron concn, occurs after chronic use of high doses of drug ... /6-Azauridine triacetyl deriv/

/SIGNS AND SYMPTOMS/ Hematopoietic suppression appears to be relatively selective for erythropoiesis, with very little if any effect noted on normal leukocyte or platelet counts. /6-Azauridine triacetyl deriv/

/SIGNS AND SYMPTOMS/ Signs of mild CNS dysfunction, incl drowsiness, lethargy, and dizziness, have been reported with lower doses, while hyperreflexia, tremor, diplopia, expressive aphasia, and dysarthria may occur at higher doses ... GI intolerance may be experienced ... /6-Azauridine triacetyl deriv/

/SIGNS AND SYMPTOMS/ ... CNS depressant effect of pyrimidine nucleoside derivatives might relate to uridine binding affinity, so called uridine receptor. /6-AZAURIDINE TRIACETYL DERIV/

For more Human Toxicity Excerpts (Complete) data for 6-AZAURIDINE (8 total), please visit the HSDB record page.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ ... 6-Azauridine /was found/ to be potent abortifacient in mice ... Most opportune time for abortifacient action in mice was during implantation of ovum.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Admin ... to pregnant mice for 3 wk resulted in no teratogenicity in first pregnancy. However, if ... admin in successive pregnancies, incr teratogenic effects were noted, which were dose-related. With high dosage resorption rate in fourth pregnancy was 100%. Consistent defect was malformation of tail.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ ... /It was reported/ that single doses of 1 mg/gm over 3 days from the 4th to the 6th day of gestation interrupted all mouse pregnancies. ... Utilizing the triacetyl derivative produced abortions and one fetus with skeletal, palate and renal defects in Rhesus monkeys.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Embryotoxic effects were compared of intramuscularly (im) and intraamniotically (ia) administered 6-azauridine (Riboazauracil Spofa) in random-bred mice H-Velaz. Effects of single doses (0.25 mg, 2.5 mg, 25.0 mg and 250.0 mg for im and 0.0025 mg, 0.025 mg and 2.5 mg for ia administration) on days 11, 12, 13 and 14 were evaluated as a sum of dead fetuses and fetuses with cleft lip and/or palate, fetuses with limb deformities and fetuses with deformities constituting the syndrome of caudal regression (hypoplasia of the caudal part of the trunk, absent tail, short tail, curled tail). Considering the sensitivity peaks of the morphogenetic processes which were observed, the dose-response relationships, the transformation of the teratogenic to a lethal effect and critical period extension with increasing doses, it was found that the effects of ia and im administered 6-azauridine did not differ. It was concluded that ia administered 6-azauridine had direct effect on embryonic morphogenetic processes and that this, too, was the essential mechanism of embryotoxicity of im administered 6-azauridine. The value of the intraamniotic technique for establishing the direct embryotoxic effect is discussed.

For more Non-Human Toxicity Excerpts (Complete) data for 6-AZAURIDINE (16 total), please visit the HSDB record page.

LD50 Cat ip 2400 mg/kg

LD50 Dog ip 3400 mg/kg

LD50 Mouse ip 11250 mg/kg

LD50 Rat ip 9400 mg/kg

For more Non-Human Toxicity Values (Complete) data for 6-AZAURIDINE (6 total), please visit the HSDB record page.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

6-Azauridine (AzUrd) is a broad-spectrum antimetabolite that inhibits both DNA and RNA virus multiplication. Prior work indicated that several AzUrd-sensitive viruses induced an increase in the level of uridine kinase, and this might explain the selective activity of AzUrd on such viruses. Present studies compared AzUrd sensitive and resistant viruses with respect to their orotic acid pathways by labeling cells with [14C]-orotic acid during the latent period of viral infection. No differences were detected by this method with either vaccinia, Newcastle disease, or vesicular stomatitis viruses. AzUrd inhibits transport of orotic acid into the cell by 30%, while incorporation of orotic acid into cellular RNA is inhibited by 50% (taking into consideration the 30% already noted) when the highest concentration of antimetabolite is used. This suggests that, in addition to blocking orotidylic acid decarboxylase, AzUrd may act on some other site (sites) of action in the inhibition of virus multiplication.

... pyrazofurin and 6-azauridine, two nucleoside analogues that are assumed to interfere with OMP decarboxylase, another enzyme involved in the biosynthesis of pyrimidine ribonucleotides, potentiate the cytocidal activity of Ce-Cyd.

Azacitidine is readily deaminated to azauridine and further degraded. It is incorporated into DNA and alters gene expression. ... Azacitidine causes hypomethylation of DNA both in vivo and in vitro.

After absorption, azaribine is almost entirely deacetylated to azur /azauridine/ in blood, with some monoacetyl deriv detectable. Peak plasma concn of azur are reached after 2 to 4 hr, and plasma disappearance curve with half-time of approx 6 to 8 hr is observed. /6-Azauridine triacetyl deriv/

L1210 cells... incubated with /6-azauridine/ AzUrd contained a new 254 nm-absorbing component, not found in control cells. It appeared to be 6-azauridine-5'-triphosphate, since it was the only peak in the triphosphate region of the chromatogram which contained 3H after incubation of cells with [3H]AzUrd.

... Azauridine is metabolized to azauracil by intestinal micoorganism ...

Azauridine undergoes intracellular conversion to 6-azauridylic acid ... /6-Azauridine triacetyl deriv/

After oral administration about 45 per cent of 2',3',5'-tri-O-acetyl-6-azauridine (TA-6-azauridine) is eliminated in the urine of rats, as well as in man, in the form of its deacetylation products. In the urine of rats, TA-6-azauridine is excreted almost exclusively in the form of free 6-azauridine whereas in man a substantial amount of mono-O-acetyl-azauridine (MA-6-azauridine) also was found. Furthermore, about 35 per cent of the dose was found in the form of MA-6-azauridine in the feces of rats collected during 48 hr after the administration. Neither TA-6-azauridine nor its deacetylation products are excreted in the bile of rats. 6-Azauracil was not detected as a deribosylation product of 6-azauridine neither in the urine or feces nor in the bile of rats under study. /6-Azauridine triacetyl deriv/

For more Metabolism/Metabolites (Complete) data for 6-AZAURIDINE (7 total), please visit the HSDB record page.

Antimetabolites that are useful in cancer chemotherapy.

Drugs used to treat or prevent skin disorders or for the routine care of skin.

Azaribine is well absorbed after oral admin ... After absorption, azaribine is almost entirely deacetylated to azur /azauridine/ in blood, with some monoacetyl deriv detectable. Peak plasma concn of azur are reached after 2 to 4 hr, and plasma disappearance curve with half-time of approx 6 to 8 hr is observed. /6-Azauridine triacetyl deriv/

Unlike azauracil, azur /azauridine/ does not cross blood-brain barrier and is not detectable in CSF. When neurotoxic manifestations have been encountered, significant concn of azauracil ... measured in CSF. Approx 95% of ingested dose of azaribine is excreted in urine as azur within 16 hr. /6-Azauridine triacetyl deriv/

2',3',5'-Triacetyl-6-azauridine was administered orally to eleven patients with far advanced neoplastic disease. The compound was absorbed rapidly from the gastrointestinal tract, in contrast to free 6-azauridine. Significant blood levels of 6-azauridine were maintained during the 8-hour period intervening between doses of the acetylated derivative. Depression of the conversion of orotic acid to uridine nucleotides was demonstrated in patients undergoing therapy, by studies of the fate of intravenously injected orotic acid-7-C14 and of the urinary excretion of orotidine and orotic acid. The metabolic effects and clinical changes observed were comparable to those produced by equivalent doses of intravenously administered 6-azauridine. /2',3',5'-Triacetyl-6-azauridine/

DISTRIBUTION OF (14)C WAS SIMILAR IN NORMAL RATS & RATS WITH ADJUVANT INDUCED POLYARTHRITIS, AFTER ADMIN OF (14)C-6-AZAURIDINE...EXCEPT THAT HEPATIC (14)C CONCN WERE TWOFOLD HIGHER IN LATTER GROUP OF ANIMALS. ABOUT 1 HR AFTER IV DOSE...TO PREGNANT RATS, FETAL CONCN OF (14)C WERE ONE-THIRD THOSE OF MATERNAL CIRCULATION.

THERAP CAT: Antipsoriatic /Former use/

A triazine nucleoside used as an antineoplastic antimetabolite. It interferes with pyrimidine biosynthesis thereby preventing formation of cellular nucleic acids. As the triacetate, it is also effective as an antipsoriatic.

Anti-metabolite used in psoriasis & mycosis fungoides /6-Azauridine triacetate/

MEDICATION /Former Use/

Research on cell formation and cancer

BIOSYNTHESIS BY E COLI IN PRESENCE OF 6-AZAURACIL.

Microbiological fermentation