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| {{drugbox | IUPAC_name = 1-methyl-1-nitroso-3-[2,4,5-trihydroxy-6- (hydroxymethyl) oxan-3-yl]-urea | image = Streptozotocin Structure NTP.png | CAS_number = 18883-66-4 | ATC_prefix = L01 | ATC_suffix = AD04 | ATC_supplemental = | PubChem = 29327 | DrugBank = APRD00209 | C=8 | H=15 | N=3 | O=7 | molecular_weight = 265.221 g/mol | bioavailability = | protein_bound = | metabolism = | elimination_half-life = 5-15 minutes | pregnancy_category = | legal_status = | routes_of_administration = }}
| | #redirect:[[�Streptozocin]] |
| {{SI}}
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| ==Overview==
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| '''Streptozotocin''' ('''Streptozocin''', '''STZ''', '''Zanosar''') is a naturally occurring [[chemical]] that is particularly toxic to the insulin-producing [[beta cell]]s of the [[pancreas]] in mammals. It is used in [[medicine]] for treating certain [[neuroendocrine tumors|cancers of the Islets of Langerhans]] and used in medical research to produce an [[animal model]] for [[Type 1 diabetes]].
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| ==Usage==
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| Streptozotocin is approved by the U.S. [[Food and Drug Administration]] (FDA) for treating [[metastatic]] cancer of the [[Islets of Langerhans|pancreatic islet cells]]. Since caries a substantial risk of toxicity and rarely cures the cancer, its use is generally limited to patients whose cancer cannot be removed by surgery. In these patients, streptozotocin can reduce the tumor size and reduce symptoms (especially [[hypoglycemia]] due to excessive [[insulin]] secretion by [[insulinoma]]s).<ref>{{cite journal | author=Brentjens R, Saltz L | title=Islet cell tumors of the pancreas: the medical oncologist's perspective | journal=Surg Clin North Am | year=2001 | pages=527-42 | volume=81 | issue=3 | id=PMID 11459269}}</ref>
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| A typical dose is 500 mg/m<sup>2</sup>/day by intravenous injection, for 5 days, repeated every 4-6 weeks.
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| ==Mechanism of action==
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| Streptozotocin is a [[glucosamine]]-[[nitrosourea]] compound. As with other [[alkylating antineoplastic agent|alkylating agents]] in the nitrosourea class, it is 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 is not recognized by the other glucose transporters. This explains its relative toxicity to beta cells, since these cells have relatively high levels of GLUT2.<ref>{{cite journal | author=Wang Z, Gleichmann H | title=GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice | journal=Diabetes | year=1998 | pages=50-6 | volume=47 | issue=1 | id=PMID 9421374}}</ref><ref>{{cite journal | author=Schnedl WJ, Ferber S, Johnson JH, Newgard CB | title=STZ transport and cytotoxicity. Specific enhancement in GLUT2-expressing cells | journal=Diabetes | year=1994 | pages=1326-33 | volume=43 | issue=11 | id=PMID 7926307}}</ref>
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| ==History==
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| Streptozotocin was originally identified in the late 1950s as an [[antibiotic]].<ref>{{cite journal | author=Vavra JJ, Deboer C, Dietz A, Hanka LJ, Sokolski WT | title=Streptozotocin, a new antibacterial antibiotic | journal=Antibiot Annu | year=1959 | pages=230-5 | volume=7 | id=PMID 13841501}}</ref> 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 {{US patent|3027300}} was granted in March 1962.
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| In the mid-1960s streptozotocin was found to be selectively toxic to the [[beta cell]]s of the [[Islets of Langerhans|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,<ref>{{cite journal | author=Mansford KR, Opie L | title=Comparison of metabolic abnormalities in diabetes mellitus induced by streptozotocin or by alloxan | journal=Lancet | year=1968 | pages=670-1 | volume=1 | issue=7544 | id=PMID 4170654}}</ref> and as a medical treatment for cancers of the beta cells.<ref>{{cite journal | author=Murray-Lyon IM, Eddleston AL, Williams R, Brown M, Hogbin BM, Bennett A, Edwards JC, Taylor KW | title=Treatment of multiple-hormone-producing malignant islet-cell tumour with streptozotocin | journal=Lancet | year=1968 | pages=895-8 | volume=2 | issue=7574 | id=PMID 4176152}}</ref> 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 Pharmaceutical Industries|Teva]]).
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| ==References==
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| <references/>
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| ==External links==
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| *{{US patent|3027300}}
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| *[http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.SearchAction&SearchType=BasicSearch&searchTerm=streptozocin FDA drug details]
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| {{Chemotherapeutic agents}}
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| [[Category:Chemotherapeutic agents]]
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| [[Category:Ureas]]
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| [[de:Streptozotocin]]
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| [[pl:Streptozotocyna]]
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| {{WH}}
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| {{WS}}
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