Streptozotocin Totally Explained

Everything about Streptozotocin totally explained

Streptozotocin (Streptozocin, STZ, Zanosar) is a naturally occurring chemical that's particularly toxic to the insulin-producing beta cells of the pancreas in mammals. It is used in medicine for treating certain cancers of the Islets of Langerhans and used in medical research to produce an animal model for Type 1 diabetes.

Usage

Streptozotocin is approved by the U.S. Food and Drug Administration (FDA) for treating metastatic cancer of the pancreatic islet cells. Since it caries a substantial risk of toxicity and rarely cures the cancer, its use is generally limited to patients whose cancer can't be removed by surgery. In these patients, streptozotocin can reduce the tumor size and reduce symptoms (especially hypoglycemia due to excessive insulin secretion by insulinomas).
A typical dose is 500 mg/m²/day by intravenous injection, for 5 days, repeated every 4-6 weeks.

Mechanism of action

Streptozotocin is a glucosamine-nitrosourea compound. As with other alkylating agents in the nitrosourea class, it's toxic to cells by causing damage to the DNA, though other mechanisms may also contribute. Streptozotocin is similar enough to glucose to be transported into the cell by the glucose transport protein GLUT2, but isn't recognized by the other glucose transporters. This explains its relative toxicity to beta cells, since these cells have relatively high levels of GLUT2.

History

Streptozotocin was originally identified in the late 1950s as an antibiotic. The drug was discovered in a strain of the soil microbe Streptomyces achromogenes by scientists at the drug company Upjohn (now part of Pfizer) in Kalamazoo, Michigan. The soil sample in which the microbe turned up had been taken from Blue Rapids, Kansas, which can therefore be considered the birthplace of streptozotocin. Upjohn filed for patent protection for the drug in August 1958 and was granted in March 1962.
In the mid-1960s streptozotocin was found to be selectively toxic to the beta cells of the pancreatic islets, the cells that normally regulate blood glucose levels by producing the hormone insulin. This suggested the drug's use as an animal model of type I diabetes, and as a medical treatment for cancers of the beta cells. In the 1960s and 1970s the National Cancer Institute investigated streptozotocin's use in cancer chemotherapy. Upjohn filed for FDA approval of streptozotocin as a treatment for pancreatic islet cell cancer in November 1976, and approval was granted in July 1982. The drug was subsequently marketed as Zanosar. Streptozotocin is now marketed by the generic drug company Sicor (Teva).

Further Information

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