| Identification | Back Directory | [Name]
Streptozocin | [CAS]
18883-66-4 | [Synonyms]
STZ
STR
strz
U-9889
ZANOSAR
nsc85998
nsc-85998
nsc-85598
nci-c03167
STREPTOZOCIN
mixedanomers
STREPTOZOSIN
streptozoticin
STREPTOZOTOCIN
estreptozocina
Streptozotocine
Streptozocin,97%
STREPTOZOCIN PURE
STZ/Streptozotocin
Streptozocin （STZ)
rcrawastenumberu206
STREPTOZOTOCIN 99.5%
Streptozotocin (STZ)
streptozocine(french)
streptozocinium(latin)
Streptozotocin (U-9889)
Streptozotocin (Zanosar)
STREPTOZOTOCIN extrapure
STREPTOZOTOCIN MIXED ANOMERS
Streptozotocin Streptozocin STZ
Zanosar, NSC85998, U9889, 1006-60
EZNA KIT ULTRA-PURE TOTAL RNA MIDI
STREPTOZOTOCIN 99.5% BIOTECH GRADE
n-d-glucosyl-(2)-n’-nitrosomethylurea
n-d-glucosyl(2)-n’-nitrosomethylharnstoff
N-(METHYLNITROSOCARBAMOYL)-A-D-GLUCOSAMINE
N-(METHYLNITROSOCARBAMOYL)-ALPHA-GLUCOSAMINE
2-deoxy-2-(3-methyl-3-nitrosoureido)-d-glucos
N-(METHYLNITROSOCARBAMOYL)-ALPHA-D-GLUCOSAMINE
Streptozocin Vetec(TM) reagent grade, 98%, powder
2-DEOXY-2-(3-METHYL-3-NITROSOUREIDO)-D-GLUCOPYRANOSE
2-Desoxy-2-(3-methyl-3-nitrosoureido)-D-glucopyranose
Glucopyranose, 2-deoxy-2-(3-methyl-3-nitrosoureido)-D-
2-deoxy-2-(((methylnitrosoamino)carbonyl)amino)-d-glucos
2-DEOXY-2-[[(METHYLNITROSOAMINO)CARBONYL]AMINO]-D-GLUCOSE
Streptozotocin, N-(Methylnitrosocarbamoyl)-α-D-glucosamine
Streptozocin, N-(Methylnitrosocarbamoyl)-alpha-D-glucosamine
D-Glucose, 2-deoxy-2-[[(methyl-nitrosoamino)-carbonyl]amino]-
2-deoxy-2-(((methylnitrosoamino)carbonyl)amino)-d-glucopyranos
2-DEOXY-2 [([METHYL-NITROSOAMINO]-CARBONYL)-AMINO]-D-GLUCOPYRANOSE
Streptozocin
2-Desoxy-2-(3-methyl-3-nitrosoureido)-D-glucopyranose
2-deoxy-2-(3-methyl-3-nitrosoureido)-alpha(andbeta)-d-glucopyranose
Streptozocin,N-(Methylnitrosocarbamoyl)-α-D-glucosamine, Streptozotocin
Streptozotocin 2-Desoxy-2-(3-methyl-3-nitrosoureido)-D-glucopyranose
3-Methyl-3-nitroso-1-[(2S,3R,4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxyMethyl)oxan-3-yl]urea
1-Methyl-1-nitroso-3-[(2S,3R,4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]urea
1-Methyl-1-nitroso-3-((2S,3R,4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxyMethyl)tetrahydro-2H-pyran-3-yl)urea | [EINECS(EC#)]
242-646-8 | [Molecular Formula]
C8H15N3O7 | [MDL Number]
MFCD00006607 | [MOL File]
18883-66-4.mol | [Molecular Weight]
265.22 |
| Chemical Properties | Back Directory | [Appearance]
off-white to pale yellow crystalline powder | [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
| [solubility ]
Soluble in DMSO (up to 25 mg/ml) or in Water (up to 25 mg/ml) | [form ]
powder | [pka]
pKa 1.3 (Uncertain) | [color ]
white to light yellow | [Water Solubility ]
soluble | [Sensitive ]
Hygroscopic | [Merck ]
13,8912 | [BRN ]
2060675 | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO or distilled water may be stored at -20°C for up to 1 month. | [InChIKey]
ZSJLQEPLLKMAKR-FEQHFJGESA-N | [CAS DataBase Reference]
18883-66-4 | [IARC]
2B (Vol. 17, Sup 7) 1987 | [EPA Substance Registry System]
D-Glucose, 2-deoxy-2-[[(methylnitrosoamino) carbonyl]amino]-(18883-66-4) |
| Hazard Information | Back Directory | [Chemical Properties]
off-white to pale yellow crystalline powder | [Definition]
ChEBI: An antibiotic that is produced by Streptomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals. | [General Description]
Off-white powder. Melting point 115°C. Used as an anti-cancer drug. Carcinogenic. | [Air & Water Reactions]
Water 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 Activity]
Antibiotic and antitumor agent. Alkylates DNA and induces diabetes mellitus via reduction of nicotinamide adenine dinucleotide in pancreatic β -cells in vivo . | [Description]
Streptozotocin (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. | [Originator]
Zanosar,Upjohn,US,1982 | [Indications]
Streptozocin (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 Process]
On 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 name]
Zanosar (Sicor). | [Therapeutic Function]
Antineoplastic | [Biochem/physiol Actions]
An N-nitroso-containing compound that acts as a nitric oxide donor in pancreatic islets; induces death of insulin-secreting cells, producing an animal model of diabetes. Potent DNA methylating agent that induces chromosomal breakage. Cytotoxic to neuroendocrine tumor cell lines that express the GLUT2 glucose transporter. | [Clinical Use]
The 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 effects]
Lacking 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. | [Veterinary Drugs and Treatments]
At 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. | [Carcinogenicity]
Streptozotocin is reasonably anticipated to be a human carcinogenbased on sufficient evidence of carcinogenicity from studies in experimental animals. | [Environmental Fate]
STZ 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. | [storage]
-20°C, protect from light, stored under nitrogen,unstable in solution, ready to use. | [Purification Methods]
Recrystallise 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 evaluation]
STZ 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. | [References]
1) Szkudelski?et al. (2001),?The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas.; Physiol. Res.,?50?537
2) Bennett & Pegg (1981),?Alkylation of DNA in rat tissues following administration of streptozotocin; Cancer Res.,?41?27861
3) Konrad?et al.?(2001),?The potential mechanism of the diabetogenic action of streptozotocin inhibition of pancreatic beta-cell O-GlcNAc-selective N-acetyl-beta-D-glucosaminidase; Biochem. J.,?356 Pt 1?31
4) Gao?et al.?(2000),?Streptozotocin-induced beta-cell death is independent of its inhibition of O-GlcNAcase in pancreatic Min6 cells; Arch. Biochem. Biophys.,?383?296
5) Kroncke & Kolb-Bachofen (1996),?Streptozotocin is not a spontaneous NO donor.; Free Radic. Res.,?24?77 |
| Safety Data | Back Directory | [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 | [Safety Profile]
Confirmed 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. | [Hazardous Substances Data]
18883-66-4(Hazardous Substances Data) | [Toxicity]
LD50 in female mice (mg/kg): 360 i.p.; 275 i.v.; in male dogs (mg/kg): 50 i.v. (Iwasaki) |
| Questions And Answer | Back Directory | [Physical and chemical properties]
Light 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 discovery]
Streptozocin 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 inducer]
Diabetes 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.
| [Uses]
It 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 .
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