Streptozotocin ,链脲菌素

A toxic glucosamine derivative, widely used for the induction of diabetes in experimental animals. The compound enters the pancreatic β cells in Langerhans islets via glucose transporter GLUT2. It has the ability to alkylate DNA and trigger the production of ROS and nitric oxide, which contribute to DNA and mitochondrial damage. Moreover, streptozocin inhibits N-acetyl-β-D-glucosaminidase and disrupts O-GlcNAc cycling. This molecule has also been used as antimicrobial compound and chemotherapeutic agent for some types of pancreatic cancer. 

Streptozotocin (STZ) is a naturally occurring chemical made from Streptomyces Achromogenes that is particularly harmful to the beta pancreas cells found in mammals. It is used in medical research as a chemotherapeutic medication to treat certain cancers of the islets that make up Langerhans. It is used in medical research to create an animal model of Type 1 Diabetes. It also acts as an antibiotic that works for Gram-positive bacteria. STZ blocks the DNA synthesis in mammals and microorganisms by cross-linking and alkylation of DNA strands and also affects all stages of the mammalian cell cycle. It is employed in medicine to treat certain cancers of those islets known as Langerhans. It is used for medical studies to create an animal model of high blood sugar and Alzheimer's disease in large doses, and also the type of diabetes, type 2, or that requires multiple small quantities.

The uses of Streptozotocin

Due to its toxicity on beta cells used in scientific research, Streptozotocin also has been used for a long time to induce diabetes and insulitis in experimental animals. 2. Streptozotocin has also been utilized to study Alzheimer's disease by modeling memory loss in mice.

Mechanism of Streptozotocin

Streptozotocin is a glucosamine-nitrosourea compound. Like other alkylating agents from the nitrosourea family, it can be harmful to cells by creating DNA damage, although other mechanisms can also play a role. Damage to DNA triggers activation of PARP, which is more likely to be a significant factor in diabetes development than damage to DNA itself. 4. Streptozotocin is comparable to glucose that it can be transported into cells by the glucose transporter GLUT2. However, it is not recognized by different glucose transporters. This is why it is toxic to beta cells since they contain significant levels of GLUT2.

The History of Streptozotocin

Streptozotocin was first identified as an antimicrobial in the latter half of 1950, the late 1950s.

In the late 1960s, Streptozotocin was selectively harmful to pancreatic beta islets. These cells regulate blood sugar levels through the production of an insulin hormone. This suggests the drug's use as a model animal for diabetes and in medical treatments for beta cell cancers.

Title: Streptozocin

CAS Registry Number: 18883-66-4

CAS Name: 2-Deoxy-2-[[(methylnitrosoamino)carbonyl]amino]-D-glucopyranose

Additional Names: 2-deoxy-2-(3-methyl-3-nitrosoureido)-D-glucopyranose; streptozotocin

Manufacturers' Codes: NSC-85998; U-9889

Trademarks: Zanosar (Pharmacia & Upjohn)

Molecular Formula: C8H15N3O7

Molecular Weight: 265.22

Percent Composition: C 36.23%, H 5.70%, N 15.84%, O 42.23%

Literature References: Isoln from Streptomyces achromogenes fermentation broth: Herr et al., Antibiot. Annu. 1959-1960, 236; Bergy et al., FR 1434920 (1966 to Upjohn), C.A. 65, 17661h (1966). Structure and synthesis: Herr et al., J. Am. Chem. Soc. 89, 4808 (1967); Hardegger et al., Helv. Chim. Acta 52, 2555 (1969); Hessler, Jahnke, J. Org. Chem. 35, 245 (1970); P. F. Wiley et al., ibid. 44, 9 (1979). Diabetogenic effect: Rakieten et al., Cancer Chemother. Rep. 29, 91 (May 1963). Comparison of streptozotocin- and alloxan-induced diabetes: C. Rerup, F. Tarding, Eur. J. Clin. Pharmacol. 7, 89 (1969). Antileukemic activity: Bhuyan et al., Cancer Chemother. Rep. Part 1 56, 709 (1972). Biosynthetic study: S. Singaram et al., J. Antibiot. 32, 379 (1979). Review and evaluation of studies of carcinogenicity in laboratory animals: IARC Monographs 4, 221-227 (1974). Toxicity data: M. Iwasaki et al., J. Med. Chem. 19, 918 (1976). Review: B. Rudas, Arzneim.-Forsch. 22, 830-861 (1972); P. F. Wiley, Anticancer Agents Based on Natural Product Models, J. M. Cassidy, J. D. Douros, Eds. (Academic Press, New York, 1980) pp 167-200. Book: Streptozotocin: Fundamentals and Therapy, M. K. Agarwal, Ed. (Elsevier/North Holland Biomedical Press, New York, 1981) 309 pp.

Properties: Pointed platelets or prisms, from 95% ethanol, mp 115° (dec). Sol in H2O, lower alcohols and ketones. uv max (ethanol): 228 nm (e 6360). A mixture of a and b anomers; aq solns rapidly undergo mutarotation to an equilibrium value of [a]D25 +39°. LD50 in female mice (mg/kg): 360 i.p.; 275 i.v.; in male dogs (mg/kg): 50 i.v. (Iwasaki).

Melting point: mp 115° (dec)

Optical Rotation: [a]D25 +39°

Absorption maximum: uv max (ethanol): 228 nm (e 6360)

Toxicity data: LD50 in female mice (mg/kg): 360 i.p.; 275 i.v.; in male dogs (mg/kg): 50 i.v. (Iwasaki)

Derivative Type: Tetraacetate

Molecular Formula: C8H11N3O7(COCH3)4

Molecular Weight: 433.37

Percent Composition: C 44.34%, H 5.35%, N 9.70%, O 40.61%

Properties: Crystals, mp 111-114° (dec). [a]D25 +41° (c = 0.78 in 95% ethanol).

Melting point: mp 111-114° (dec)

Optical Rotation: [a]D25 +41° (c = 0.78 in 95% ethanol)

CAUTION: Streptozocin is reasonably anticipated to be a human carcinogen: Report on Carcinogens, Eleventh Edition (PB2005-104914, 2004) p III-234.

Use: Production of experimental diabetes in laboratory animals.

Therap-Cat: Antineoplastic.

Keywords: Antineoplastic; Antibiotics and Analogs.

COA:

Product name: Streptozotocin; N-(Methylnitrosocarbamoyl)-D-glucosamine          

CAS: 18883-66-4      M.F.: C₈H₁₅N₃O₇          M.W._: 265.22