When exposed to diazoserine (100 μg/mL for six hours), certain organisms experience morphological changes, such as the characteristic elongation of Candida albicans cells [2]. Azaserine (0–10 μM) stops E. coli from growing. coli strains for UTH 4, UTH 7036, UTH 7048, and UTH 7049 having MIC values of 12.11, 51.9, 69.2, and 69.2 μg/mL [3].

Rats given intraperitoneal injections of diazoserine (5 mg/kg) once or twice a week for six months develop tumors [1].

Animal/Disease Models: Wistar rat[1]
Doses: 5 mg/kg
Route of Administration: intraperitoneal (ip) injection; 5 mg/kg once or twice a week for 6 months
Experimental Results: After 1 year, most of the treated rats The rat pancreas was diffusely abnormal and contained numerous hyperplastic nodules and adenomas, and more than one-quarter of the rats developed pancreatic cancer.

Absorption, Distribution and Excretion
VET: ORAL ABSORPTION IS POOR.
... AFTER TREATMENT OF RATS WITH (3)H-AZASERINE THE PANCREAS HAS BEEN SHOWN TO ATTAIN HIGH LEVELS OF RADIOACTIVITY.

Interactions
Chemoprevention by a synthetic retinoid, selenium, and these agents in combination during the postinitiation stages of carcinogenesis induced in rats by azaserine was evaluated. Male Lewis rats were given three weekly injections of 30 mg/kg azaserine while being fed a purified diet. One week after completion of carcinogen treatment, groups of rats were switched to the purified diet supplemented with either a retinoid, N-(2-hydroxethyl)retinamide, at a level of 0.5 or 1 mmol/kg diet, or with 5 ppm sodium selenite, or with a combination of retinoid and selenium. One year after the diet change, the incidence of pancreatic and other neoplasms was determined by autopsy and histologic study. The incidence of pancreatic carcinoma (including carcinoma-in-situ, CIS) among nonretinoid-treated controls was 68%. Since the dietary supplements were fed after completion of exposure to the carcinogen, the effects on both pancreatic and liver carcinogenesis were exerted during postinitiation phase of carcinogenesis. As in previous studies, the retinoid inhibited the progression of pancreatic carcinogenesis in a dose-related fashion. Selenium alone had no effect. However, the combination of retinoid plus selenium was more effective than retinoid alone, although the increase in inhibition was not large. The retinoid was also found to inhibit liver carcinogenesis induced by azaserine. Selenium, either alone or in combination with retinoid, was ineffective.
Effect of dietary intake of fish (menhaden) oil and fish (cod) protein on the development of pancreatic preneoplastic lesions was examined in male Wistar rats. Fourteen day old animals were given a single ip injection of 30 mg L-azaserine/kg body weight; diazoacetate serine (ester). At 21 days of age they were weaned and maintained on dietary treatment for 4 months. Fish protein did not appear to produce a significantly different preneoplastic response when compared to casein as a protein source. However, a 20% menhaden oil diet, rich in omega 3 fatty acids, produced a significant decrease in the development of both the size and number of preneoplastic lesions when compared to a 20% corn oil diet rich in omega 6 fatty acids. This study provides evidence that fish oils, rich in omega 3 fatty acids, may have potential as inhibitory agents in cancer development.
Diets containing raw soybean products fed ad libitum caused a reduction in food consumption and growth, pancreatic enlargement, hypersecretion of digestive enzymes, and enlargement of intestinal segments and their contents in rats, chicks and geese. These effects were found to be related to the concentration of trypsin inhibitor in the diet. ... In long-term studies the incidence of pancreatic nodules was correlated to the level of trypsin inhibitor in the diet. Feeding raw soybean products potentiated the carcinogenic effect of azaserine and meal feeding enhanced the incidence and size of the pancreatic nodules in rats fed raw soybean products.
Effects of coffee and dietary fat (alone and in combination) on the development of preneoplastic lesions in exocrine pancreas were investigated in rats and hamsters, treated with azaserine or N-nitrosobis(2-oxopropyl)amine, respectively. Animals were given the respective diets (5% or 25% corn oil) and coffee (instead of drinking water) within one week after the treatment with carcinogen. At four months postinitiation, the pancreata were quantitatively examined for the number and size of preneoplstic foci. In rats, coffee alone inhibited growth of acidophilic foci and, moreover, slightly inhibited the positive modulating effect of fat on growth of these foci, pointing to a negative rather than a positive interaction between these two life-style factors. In hamsters, coffee alone enhanced growth of cystic foci, whereas fat alone enhanced growth of ductular foci. An interaction between fat and coffee on pancreatic carcinogenesis in hamsters could not be demonstrated.
For more Interactions (Complete) data for AZASERINE (8 total), please visit the HSDB record page.

[1]. Longnecker DS, Curphey TJ. Adenocarcinoma of the pancreas in azaserine-treated rats. Cancer Res. 1975 Aug;35(8):2249-58.

[2]. Screening of Antifungal Antibiotics According to Activities Inducing Morphological Abnormalities. Agric. Biol Chem., 47 (9), 2061-2069, 1983.

[3]. Williams MV, Tritz GJ. Studies on the modes of action of azaserine inhibition of Escherichia coli. Potentiation of phenylalanine reversal. J Antimicrob Chemother. 1977 Jan;3(1):65-77.

[4]. Azaserine, DON, and azotomycin: three diazo analogs of L-glutamine with clinical antitumor activity. Cancer Treat Rep. 1979 Jun;63(6):1033-8.

[5]. Cytotoxic mechanisms of glutamine antagonists in mouse L1210 leukemia. J Biol Chem. 1990 Jul 5;265(19):11377-81.

Azaserine can cause cancer according to an independent committee of scientific and health experts.
Azaserine appears as pale yellow to green crystals. Used as an antifungal agent.
Azaserine is a carboxylic ester resulting from the formal condensation of the carboxy group of diazoacetic acid with the alcoholic hydroxy group of L-serine. An antibiotic produced by a Streptomyces species. It has a role as an antimicrobial agent, an antineoplastic agent, an antifungal agent, an antimetabolite, an immunosuppressive agent, a metabolite and a glutamine antagonist. It is a diazo compound, a carboxylic ester, a L-serine derivative and a non-proteinogenic L-alpha-amino acid.
Azaserine has been reported in Streptomyces with data available.
Azaserine is a naturally occurring serine derivative diazo compound with antineoplastic properties, Azaserine functions as a purine antagonist and glutamine analogue (glutamine amidotransferase inhibitor) that competitively inhibits pathways in which glutamine is metabolized. An antibiotic and antitumor agent, Azaserine is used in clinical studies as a potential antineoplastic agent. (NCI04)
Antibiotic substance produced by various Streptomyces species. It is an inhibitor of enzymatic activities that involve glutamine and is used as an antineoplastic and immunosuppressive agent.

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Mechanism of Action
AMINO ACID ANTAGONISTS INHIBIT PROTEIN & NUCLEIC ACID SYNTHESIS BY INTERFERING WITH INCORPORATION OF SPECIFIC AMINO ACIDS REQUIRED FOR PROTEIN OR NUCLEIC ACID SYNTHESIS. THESE CMPD INCL ... AZASERINE ... .
THE GLUTAMINE ... /ANTAGONIST/ AZASERINE ... POTENT ... /INHIBITOR/ OF DE-NOVO PATHWAY OF PURINE NUCLEOTIDE BIOSYNTHESIS. ... INHIBIT/S/ PURINE BIOSYNTHESIS THROUGH FORMATION OF COVALENT BONDS WITH CYSTEINE RESIDUE IN ACTIVE SITE OF KEY ENZYME IN PATHWAY, FORMYLGLYCINAMIDE RIBOTIDE AMIDOTRANSFERASE.
VET: INHIBITS GLUTAMINE USE IN ASPARAGINE BIOSYNTHESIS & IV OR IP USE ENHANCES EFFECT OF L-ASPARAGINASE AGAINST EXPTL SOLID TUMORS. ... ANTIDIURETIC ACTION NOTED IN MICE.
4 ESTABLISHED CELL LINES CONTAINING GAMMA-GLUTAMYL TRANSPEPTIDASE. /A/ POSITIVE CORRELATION WAS OBSERVED BETWEEN CELLULAR GAMMA-GLUTAMYL TRANSPEPTIDASE LEVELS AND SENSITIVITY TO AZASERINE TOXICITY. STRAINS EXPRESSING LOWEST GAMMA-GLUTAMYL TRANSPEPTIDASE ACTIVITIES SHOWED GREATEST RESISTANCE TO AZASERINE TOXICITY.

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Therapeutic Uses
Antibiotics, Antifungal; Antibiotics, Antineoplastic; Antimetabolites; Antimetabolites, Antineoplastic; Carcinogens; Immunosuppressive Agents
THE GLUTAMINE ANTAGONISTS AZASERINE ... /HAS/ ONLY WEAK CYTOSTATIC ACTIVITY WHEN USED ALONE ... /BUT/ CAN PRODUCE SIGNIFICANT POTENTIATION WHEN ADMIN WITH PURINE ANALOGS SUCH AS MERCAPTOPURINE OR THIOGUANINE.
AZASERINE HAS BEEN TESTED AS AN INHIBITOR OF PURINE SYNTHESIS, & IN CONJUNCTION WITH MERCAPTOPURINE, IN TREATMENT OF ACUTE CHILDHOOD LEUKEMIA.
MEDICATION (VET): IN LIMITED NUMBER OF EXPTL CASES AS ANTIMETABOLITE IN TUMOR THERAPY SINCE MORE EFFECTIVE DRUGS HAVE REPLACED IT.
For more Therapeutic Uses (Complete) data for AZASERINE (6 total), please visit the HSDB record page.

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Drug Warnings
VET: FETAL TOXICITY ASSOC WITH ITS USE ... NARROW MARGIN BETWEEN EFFECTIVE & TOXIC DOSES.

C5H7N3O4

173.12678

173.043

115-02-6

460129

White to yellow solid powder

146-162° (dec)

-1.37

2

6

5

12

233

1

C([C@@H](C(=O)O)N)OC(=O)C=[N+]=[N-]

MZZGOOYMKKIOOX-VKHMYHEASA-N

InChI=1S/C5H7N3O4/c6-3(5(10)11)2-12-4(9)1-8-7/h1,3H,2,6H2,(H,10,11)/t3-/m0/s1

(S)-2-amino-3-(2-diazoacetoxy)propanoic acid

CN-15757 P165 O-Diazoacetyl-L-serine P-165 CL-337P 165CL337diazoacetate (ester) LSerine diazoacetylserine serine diazoacetate AZAS AZS

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~50 mg/mL (~288.80 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)