Basic information Physical and chemical properties History of discovery Animal diabetes inducer Uses Safety Related Supplier
Streptozotocin Chemical Properties
- Melting point:121 °C (dec.) (lit.)
- alpha D25 +39°
- Boiling point:408.44°C (rough estimate)
- Density 1.4410 (rough estimate)
- refractive index 1.6500 (estimate)
- storage temp. -20°C
- form powder
- pkapKa 1.3 (Uncertain)
- color white to light yellow
- Water Solubility soluble
- Sensitive Hygroscopic
- Merck 13,8912
- BRN 2060675
- CAS DataBase Reference18883-66-4
- IARC2B (Vol. 17, Sup 7) 1987
- EPA Substance Registry SystemStreptozotocin (18883-66-4)
- Hazard Codes Xn,T
- Risk Statements 40-61-46-45-22-20/21/22
- Safety Statements 36/37-53-45-36-22
- RIDADR 3249
- WGK Germany 3
- RTECS LZ5775000
- F 3-10-21
- HazardClass 6.1(b)
- PackingGroup III
- HS Code 29419090
- Hazardous Substances Data18883-66-4(Hazardous Substances Data)
- ToxicityLD50 in female mice (mg/kg): 360 i.p.; 275 i.v.; in male dogs (mg/kg): 50 i.v. (Iwasaki)
Streptozotocin Usage And Synthesis
- Physical and chemical propertiesLight yellow crystalline powder, soluble in water, but its water solution is very unstable at room temperature,which can be broken down intothe gas evaporates after a half-hour , it takes using now. Dissolved in lower alcohols and ketones degrees, insoluble in polar organic solvents.
- History of discoveryStreptozocin is produced by streptococcal bacteria ,it is natural compound which has a specific toxicity on mammalian insulin-producing pancreas islet B cells, it is a nitrosourea antibiotic, it is different from fat-soluble nitrosourea ,in chloroethyl place it is a methyl group at the other end of the molecule it is an amino sugar, Streptozocin can break down reactive methyl positive carbon ions alone, and forms cross-links between the chains with DNA , so that it can lead to the DNA alkylation, but its alkylation is weaker than other nitrosourea drugs, and its metabolite methylsulfinyl nitrosourea’s alkylation is 3 to 4 times stronger than its STZ . STZ can form isocyanates in the body . It can combine with Nucleic acid protein and thereby inhibit DNA polymerase vitality,to make it difficult to repair damaged DNA. In the late 1950s,it was discovered at the beginning considered to be an antibiotic, scientists from the pharmaceutical company Upjohn in Kalamazoo (now a subsidiary of Pfizer) found STZ in the soil Streptomyces strains. In the mid-1960s, it was discovered that Streptozocin has specific toxicity on insulin-producing pancreatic B cells . This discovery makes STZ later used in animal model of diabetes and used to treat pancreatic B cell tumors.from 1860s to the 1870s, the US National Cancer Institute began to study Streptozocin application in chemotherapy. Upjohn Company in November 1976 applied for FDA approval for its treatment of pancreatic cancer, and in July 1982 it was approved. After that ,it has been using the trade name Zanosar. It is used to treat pancreatic islet cell tumors (β cells or non-β cell carcinoma) clinically, it has a certain effect on for carcinoid tumor, Hodgkin's disease, colon cancer and liver cancer . It is used to Establish an animal model of type 1 diabetes in medical research.
- Animal diabetes inducerDiabetes is a common metabolic endocrine disease, the main causes are due to relative or absolute lack of insulin, which is characterized by high blood sugar and diabetes. Experimental drugs can be used (such as alloxan and Streptozocin , etc.) to selectively destroy pancreatic β-cells, resulting in elevated blood glucose levels to make experimental diabetic mice.
Streptozocin (referred STZ) is a induced diabetic agent , it has an selectively destructive effect on a certain species of animals islet β cells ,which can induce diabetes in many animals, but they do not include the guinea pigs and humans, the general manufacture of animal models usually uses rats and mice. Foreign scholars reported that the incidence of diabetes in male rats selected manufacturing model is significantly higher than in female rats. Type 1 diabetes and type 2 diabetes animal models preparation is related to STZ injection dose: when bolus injection, as a direct result of the extensive destruction of pancreatic β cells,it can cause type 1 diabetes model; and when a relatively small amount STZ injection, since it just destroys part of the islet β cell function, resulting in peripheral tissues insensitive to insulin , while giving high-calorie diet, the combination will induce a animal model whose pathological, physiological changes are both close to human type 2 diabetes.
The above information is edited by the Chemicalbook of Tian Ye.
- UsesIt is a compound containing N-nitroso ,it acts as a nitric oxide donor in pancreatic islets ; it can induce the death of diabetic animal model style of insulin-secreting cells . Efficient DNA methylation agent, can induce chromosome breakage.it has cell toxicity On the neuroendocrine tumor cell lines with the expression of GLUT2 glucose transporter (GLUT2 glucose transporter) . Streptozocin is used for inducing Type 1 diabetes in Medical researches .
- DescriptionStreptozotocin (STZ) was originally identified in the late 1950s as an antibiotic and was discovered in a strain of the soil microbe Streptomyces achromogenes. In the mid-1960s, STZ was found to be selectively toxic to the beta cells of the pancreatic islets and thus it is used in animal model of diabetes and as a medical treatment for cancers of the beta cells. STZ’s use in cancer chemotherapy received Food and Drug Administration approval in July 1982 and the drug was subsequently marketed as Zanosar.
- Chemical Propertiesoff-white to pale yellow crystalline powder
- Usesantineoplastic, alkylating agent
- UsesStreptozotocin is used in the treatment metastatic cancer of the pancreatic islet cells. Streptozotocin has a highlrisk of toxicity and is generally limited to cancers that are inoperable.
- UsesStreptozotocin is an unusual aminoglycoside containing a nitrosoamino group produced by Streptomyces achromogenes and discovered in 1959 as an antibiotic. The nitrosoamino group enables the metabolite to act as a nitric oxide (NO) donor. NO is an important messenger molecule involved in many physiological and pathological processes in the body. Streptozotocin is also widely used to induce diabetes in rodent models by inhibition of β-cell O-GlcNAcase.
- Usessomatostatin octapeptide analog
- DefinitionChEBI: An antibiotic that is produced by Streptomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals.
- IndicationsStreptozocin (Zanosar), a water-soluble nitrosourea
produced by the fungus Streptomyces achromogenes,
acts through methylation of nucleic acids and proteins.
In addition, it produces rapid and severe depletion of
the pyridine nucleotides nicotinamide adenine dinucleotide
(NAD) and its reduced form (NADH) in liver
and pancreatic islets.
Streptozocin is not well absorbed from the gastrointestinal tract and must be administered intravenously or intraarterially. In preclinical studies, the plasma half-life was 5 to 10 minutes.
Streptozocin produces remission in 50 to 60% of patients with islet cell carcinomas of the pancreas. It is also useful in malignant carcinoid tumors.
Almost all patients have nausea and vomiting. The major toxicity is renal tubular damage, which may be severe in 5 to 10% of patients taking streptozocin. Treatment of metastatic insulinomas may result in the release of insulin from the tumor and subsequent hypoglycemic coma. Less severe toxicities include diarrhea, anemia, and mild alterations in glucose tolerance or liver function tests.
- Manufacturing ProcessOn a sterile maltose-tryptone agar slant of the following composition: 1 g
maltose; 0.5 g tryptone; 0.05 g K2HPO4; 0.01 g FeSO4·7H2O; 1.5 g agar; and
sufficient distilled water to make 100 ml, Streptomyces achromogenes var.
streptozoticus was grown for 7 days at 28°C.
The culture thus produced was used as an inoculum for the following sterile medium: 1 g glucose; 1 g beef extract; 0.5 g Bacto peptone (Difco); 0.5 g NaCl; and sufficient distilled water to make 100 ml. The pH was adjusted to 7.0 before sterilization. The inoculated medium was incubated in shake flasks for 3 days at 28°C on a reciprocating shaker and 75 ml of the resulting growth was used to inoculate 12 l of sterile medium of the same formulation. The medium was incubated in a 20 l stainless steel bottle, at 28°C for 2 days, the contents being stirred continuously with sparged air at the rate of 6 l of free air per minute. The resulting growth was used to inoculate 250 l of the following sterile medium. 2 g Bacto peptone (Difco); 2.5 g blackstrap molasses; 2 g glucose; 0.25 g NaCl; and sufficient distilled water to make 100 ml. The pH was adjusted to 7.0 before sterilization.
This medium was incubated in a 100 gallon stainless steel fermentor, at 24°C with sparged air being introduced at the rate of 50 l/min and with agitation by an impeller. After 66 hours of fermentation the beer was harvested. To 100 gallons of harvested beer was added 17 pounds of diatomite, and 35 pounds of activated carbon. The mixture was stirred well and then filtered, the cake was water-washed with 10 gallons of tap water, and then washed with 25 gallons of acetone followed by 30 gallons of 1:1 aqueous acetone. The acetone solutions of streptozotocin were pooled and dried in vacuo to 3.88 pounds.
- brand nameZanosar (Sicor).
- Therapeutic FunctionAntineoplastic
- General DescriptionStreptozocin is available in 1-g vials for IV administrationin the treatment of metastatic islet cell carcinoma of the pancreas,colon cancer, and Hodgkin’s disease. Activation resultsin the formation of methyl carbonium ions, which alkylateDNA, but the agent is less effective in alkylating DNAand carbamylating proteins than other nitrosoureas, which isbecause in part of an intramolecular carbamoylation. The internalcarbamate group migration occurs via the hydroxylgroups of the glucose portion of the molecule. There is a reducedeffect on RNA function compared with other nitrosoureasas well. The hydrophilic agent is rapidly clearedfrom the plasma with an elimination half-life of 35 minutes.The presence of the glucose moiety allows for utilization ofglucose transporters, which concentrate the compound inthe -cells of the pancreas. The metabolism of the agent hasnot been well characterized. Renal toxicity is dose limitingand may present initially as proteinuria and azotemia butmay progress to renal failure. Nausea and vomiting may besevere with the agent, whereas myelosuppression is generallymild. Normal glucose metabolism may be altered sothat hypoglycemia or hyperglycemia may be seen. In someanimal species, streptozocin produces diabetes but muchmilder effects are seen in man.
- General DescriptionOff-white powder. Melting point 115°C. Used as an anti-cancer drug. Carcinogenic.
- Air & Water ReactionsWater soluble.
- Reactivity Profile[D-GLUCOSE, 2-DEOXY-2-[[(METHYLNITROSOAMINO)-CARBONYL]AMINO] is weakly basic. Reacts exothermically with acids. Reacts with both strong oxidizing agents and strong reducing agents.
- Biological ActivityAntibiotic and antitumor agent. Alkylates DNA and induces diabetes mellitus via reduction of nicotinamide adenine dinucleotide in pancreatic β -cells in vivo .
- Clinical UseThe glucopyranose moiety of streptozocin confers both islet cell specificity and high water solubility to this nitrosourea-based antineoplastic. As a result, it is used exclusively in metastatic islet cell carcinoma of the pancreas and is administered IV in D5W or normal saline.
- Side effectsLacking the 2-chloroethyl substituent of carmustine and lomustine, it is much less reactive as a DNA alkylating agent, and myelotoxicity is relatively rare but not unknown. Cumulative, dose-related renal toxicity can be severe or fatal, however, and 67% of patients receiving this drug will exhibit some kidney-related pathology.
- Safety ProfileConfirmed carcinogen with experimental carcinogenic, neoplas tigenic, tumorigenic, and teratogenic data. Experimental poison by intravenous, parenteral, subcutaneous, and intraperitoneal routes. Moderately toxic to humans by intravenous route. Human systemic effects: nausea or vomiting, impaired liver function, kidney changes. Human mutation data reported. Experimental reproductive effects. When heated to decomposition it emits toxic fumes of NOx. See also NITROSAMINES.
- Veterinary Drugs and TreatmentsAt present the primary purpose for streptozocin use in veterinary medicine is as a treatment for insulinomas in dogs, particularly those with refractory hypoglycemia and when tumors are nonresectable or have metastasized. Streptozocin potentially could be used for other oncologic conditions as well.
- CarcinogenicityStreptozotocin is reasonably anticipated to be a human carcinogenbased on sufficient evidence of carcinogenicity from studies in experimental animals.
- Environmental FateSTZ is an odorless ivory-colored crystalline powder or pale yellow crystals. Having the solubility of 5070 mg l-1 in water at 25 °C, STZ is soluble in alcohol and ketones and slightly soluble in polar organic solvents and insoluble in nonpolar organic solvents. STZ is produced by the soil microorganism and therefore isolated from soil samples that assumed a source of release to the environment. Vapor pressure and Henry’s law constant of STZ are 1.74E-12 mm Hg and 1.08E-10 cm3 per molecule-sec at 25 °C, respectively. No information is currently available for partition behavior in water, sediment, and soil; environmental persistency, long-range transport, or bioaccumulation/ biomagnification.
- Purification MethodsRecrystallise streptozotocin from 95% EtOH. It is soluble in H2O, MeOH and Me2CO. It has UV max at 228nm ( 6360) in EtOH. The tetraacetate has m 111-114o(dec), and  D 25 +41o (c 0.78, 95% EtOH) after recrystallisation from EtOAc. [Herr et al. J Am Chem Soc 89 4808 1967, NMR: Wiley et al. J Org Chem 44 9 1979.] It is a potent methylating agent for DNA [Bennett & Pegg Cancer Res 41 2786 1981].
- Toxicity evaluationSTZ as an antibiotic is effective against Gram-negative bacteria. As a diabetogenic agent, STZ by its N-nitroso group acts as a nitric oxide donor in pancreatic islets. STZ inhibits synthesis of DNA in microorganisms and mammalian cells by alkylation and cross-linking the strands of DNA, and also affects on all stages of mammalian cell cycle. STZ-induced DNA damage causes activation of poly ADP-ribosylation, which is important in induction of diabetes rather than DNA damage. Biochemical studies indicated that STZ inhibits pyridine nucleotides and the key enzymes that are involved in glyconeogenesis. STZ transports glucose into the cell by the glucose transport protein GLUT2, but is not recognized by the other glucose transporters. Since beta cells have relatively high levels of GLUT2, this explains STZ’s relative toxicity in these cells.
- Streptomycin <>STREPTOZOTOCIN CRYSTALLINE Streptozotocin tetraacetate 500 MG STREPTOZOCIN PURE 4,6-ethylidene glucose streptozotocin STREPTOZOTOCIN (ANTIBIOTIC Chlorozotocin TETRAHYDROPYRAN-2-METHANOL (S)-3-Aminobutan-1ol Glucose oxidase Abamectin ALTRENOGEST Methyl PYRAZOPHOS Streptozotocin CORN SYRUP Centchroman glucopyranose
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