Streptozocin
(Synonyms: 链脲佐菌素; Streptozotocin; U 9889) 目录号 : GC17131
A diabetogenic agent which targets beta cells
Cas No.:18883-66-4
Sample solution is provided at 25 µL, 10mM.
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| Cell experiment [1]: | |
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Cell lines |
islet cells |
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Preparation Method |
Monolayer cultures of islet cells from neonatal rats were exposed to concentrations of MNU and STZ (Streptozocin) of 1, 2, 5, or 10 mM, and the activity of the enzyme was assayed. |
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Reaction Conditions |
1, 2, 5, or 10 mM |
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Applications |
Streptozocin is toxic to cultured p-cells at a concentration of 1 mM. |
| Animal experiment [2]: | |
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Animal models |
Female mice |
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Preparation Method |
Female mice received a single subdiabetogenic dose of streptozocin (65 mg/kg intraperitoneally) 8-11 days or 14-17 days before fertilization. |
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Dosage form |
65 mg/kg; i.p. |
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Applications |
Morphological analysis of preimplantation embryos collected on day 3 of pregnancy revealed significant changes in the distribution pattern of preimplantation embryo stages recovered from streptozocin-treated females. |
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References: [1]. Wilson GL, et al. Mechanisms of nitrosourea-induced beta-cell damage. Activation of poly (ADP-ribose) synthetase and cellular distribution. Diabetes. 1988 Feb;37(2):213-6. [2]. Veselá J, et al. Subdiabetogenic streptozocin treatment impairs preimplantation development of mouse embryos. Physiol Res. 1993;42(1):23-7. |
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Streptozocin, a potent DNA-methylating antibiotic, is a naturally occurring nitrosoamide used for extensively to produce diabetes in experimental models.[1]
In vitro, STZ was toxic with IC50 values of 11.7, 904 and 1024 μg/ml for HL60, K562 and C1498 cells respectively.[3]
In vivo efficacy test it shown that when combined with a protocol for induction of diuresis, dogs were treated safely with 500 mg/m2 of streptozocin, intravenously, every 3 weeks, and it may be have a potential efficacy on the treatment of dogs with metastatic pancreatic islet cell tumors.[1]
In vivo experiment it indicated that mice were administrated streptozocin with 65 mg/kg intraperitoneally for 8-11 days or 14-17 days, streptozocin improved the impaired development of preimplantation embryos on 8-11 days. However, after 14-17 days, the incidence of degenerated embryos was increased in both streptozocin-treated mice groups.[2] Treatment with 60 mg/kg of streptozocin intravenously also induces an early hyperglycaemia when the hepatic glycogen storage is almost depleted that is during the fasting state.[4] For the treatment of advanced islet-cell carcinoma, the combination of streptozocin and doxorubicin is more efficious than the current standard regimen of streptozocin plus fluorouracil.[5] There is little value for patients with malignant carcinoid tumors by combination treatment with streptozocin and 5-fluorouracil.[6]
References:
[1].Moore AS, et al. Streptozocin for treatment of pancreatic islet cell tumors in dogs: 17 cases (1989-1999). J Am Vet Med Assoc. 2002 Sep 15;221(6):811-8.
[2].Veselá J, et al. Subdiabetogenic streptozocin treatment impairs preimplantation development of mouse embryos. Physiol Res. 1993;42(1):23-7.
[3].Diab RA, et al. Immunotoxicological effects of streptozotocin and alloxan: in vitro and in vivo studies. Immunol Lett. 2015 Feb;163(2):193-8.
[4].Wong KK. Reduction by streptozocin of blood glucose utilization during the appearance of the streptozocin induced early hyperglycaemia in fasting rats. Biochem Mol Biol Int. 1996 May;39(1):191-5.
[5].Moertel CG, et al. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1992 Feb 20;326(8):519-23.
[6].Oberg K, et al. Cytotoxic treatment in patients with malignant carcinoid tumors. Response to streptozocin--alone or in combination with 5-FU. Acta Oncol. 1987;26(6):429-32.
Streptozocin 是一种有效的 DNA 甲基化抗生素，是一种天然存在的亚硝基酰胺，在实验模型中广泛用于产生糖尿病。[1]
在体外，STZ 对 HL60、K562 和 C1498 细胞的 IC50 值分别为 11.7、904 和 1024 μg/ml。[3]
体内功效测试表明，当与诱导利尿方案相结合时，狗可以安全地每 3 周静脉注射 500 mg/m2 链佐星，并且它可能对治疗患有转移性胰岛细胞瘤的狗。[1]
体内实验表明，给小鼠腹腔注射65 mg/kg链脲佐菌素8-11天或14-17天，链脲佐菌素在8-11天改善着床前胚胎发育受损。然而，在 14-17 天后，两个接受链脲佐菌素治疗的小鼠组的退化胚胎发生率都增加了。[2] 静脉注射 60 mg/kg 链佐佐星也可诱导早期高血糖症，此时肝糖原储存在禁食状态下几乎耗尽。[4]对于晚期胰岛细胞癌的治疗，链佐星和多柔比星的组合比目前链佐星加氟尿嘧啶的标准方案更有效.[5]链脲佐菌素与5-氟尿嘧啶联合治疗恶性类癌患者价值不大。[6]
| Cas No. | 18883-66-4 | SDF | |
| 别名 | 链脲佐菌素; Streptozotocin; U 9889 | ||
| 化学名 | 1-methyl-1-nitroso-3-[2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]urea | ||
| Canonical SMILES | CN(C(=O)NC1C(C(C(OC1O)CO)O)O)N=O | ||
| 分子式 | C8H15N3O7 | 分子量 | 265.22 |
| 溶解度 | ≥ 10.3mg/mL in DMSO, ≥ 53.2mg/mL in Water, ≥ 26.5mg/mL in EtOH with gentle warming | 储存条件 | -20°C, protect from light, stored under nitrogen,unstable in solution, ready to use. |
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.7705 mL | 18.8523 mL | 37.7045 mL |
| 5 mM | 0.7541 mL | 3.7705 mL | 7.5409 mL |
| 10 mM | 0.377 mL | 1.8852 mL | 3.7705 mL |
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The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas
Physiol Res.2001;50(6):537-46.PMID:11829314
Alloxan and streptozotocin are widely used to induce experimental diabetes in animals. The mechanism of their action in B cells of the pancreas has been intensively investigated and now is quite well understood. The cytotoxic action of both these diabetogenic agents is mediated by reactive oxygen species, however, the source of their generation is different in the case of alloxan and streptozotocin. Alloxan and the product of its reduction, dialuric acid, establish a redox cycle with the formation of superoxide radicals. These radicals undergo dismutation to hydrogen peroxide. Thereafter highly reactive hydroxyl radicals are formed by the Fenton reaction. The action of reactive oxygen species with a simultaneous massive increase in cytosolic calcium concentration causes rapid destruction of B cells. Streptozotocin enters the B cell via a glucose transporter (GLUT2) and causes alkylation of DNA. DNA damage induces activation of poly ADP-ribosylation, a process that is more important for the diabetogenicity of streptozotocin than DNA damage itself. Poly ADP-ribosylation leads to depletion of cellular NAD+ and ATP. Enhanced ATP dephosphorylation after streptozotocin treatment supplies a substrate for xanthine oxidase resulting in the formation of superoxide radicals. Consequently, hydrogen peroxide and hydroxyl radicals are also generated. Furthermore, streptozotocin liberates toxic amounts of nitric oxide that inhibits aconitase activity and participates in DNA damage. As a result of the streptozotocin action, B cells undergo the destruction by necrosis.
Streptozotocin, 1982-2022: Forty Years from the FDA's Approval to Treat Pancreatic Neuroendocrine Tumors
Neuroendocrinology.2022;112(12):1155-1167.PMID:35537416DOI: 10.1159/000524988.
In May 1982, the US Food and Drug Administration (FDA) approved the use of streptozotocin to treat pancreatic neuroendocrine tumors (panNETs). Thus, this year marks 40 years since that landmark date. This review of streptozotocin to treat panNETs is intended to commemorate this anniversary. A historical perspective of the chemical structure, pharmacokinetics, and mechanism of action of streptozotocin is followed by data from prospective and retrospective clinical studies. The last section of the review addresses the latest aspects and takes note of the prospects that lie ahead on the future horizon of the use of streptozotocin to treat panNETs, including ongoing clinical trials.
Streptozotocin-induced diabetic models in mice and rats
Curr Protoc Pharmacol.2008 Mar;Chapter 5:Unit 5.47.PMID:22294227DOI: 10.1002/0471141755.ph0547s40.
Streptozotocin (STZ) is an antibiotic that can cause pancreatic β-cell destruction, so it is widely used experimentally as an agent capable of inducing insulin-dependent diabetes mellitus (IDDM), also known as type 1 diabetes mellitus (T1DM). This unit describes protocols for the production of insulin deficiency and hyperglycemia in mice and rats, using STZ. These models for diabetes can be employed for assessing the mechanisms of T1DM, screening potential therapies for the treatment of this condition, and evaluation of therapeutic options.
Streptozotocin: its excretion and metabolism in the rat
Diabetologia.1976 Oct;12(5):483-8.PMID:135705DOI: 10.1007/BF01219512.
The excretion of radioisotope following the administration of three specifically 14C-labelled forms of streptozotocin was investigated in the rat using ureter and bile duct cannulation techniques. The urine collected during the first hour following the administration of the drug contained the highest proportion of injected radioactivity (approximately 34% with (3'-methyl-14C)-streptozotocin and approximately 40% each with (1-14C)-and (2'-14C)-streptozotocin. Over the entire experimental period (6 hours), approximately 70% of the injected radioactivity of (1-14C)- and (2'-14C)-streptozotocin appeared in the urine. With (3'-methyl-14C)-streptozotocin, only 53% of the injected radioactivity appeared in the urine over the same period. In contrast to the high urinary excretion, less than 3% of the injected radioactivity from all three radiolabelled streptozotocin samples appeared in the bile. The in vivo and in vitro metabolism of streptozotocin was also investigated. In addition to substantial amounts of unchanged drug, three radiolabelled metabolites (two major and one minor) were detected in the urine during the 6 hour collection period following the administration of (1-14C)- and (2'-14C)-streptozotocin. In contrast, only unchanged (3'-methyl-14C)-streptozotocin was detected in the urine collected over the same period following the administration of the methyl labelled drug. The two major metabolites were also produced when (1-14C)-and (2'-14C)-streptozotocin were incubated with a rat liver supernatant fraction (100,000 X g). The liver was further demonstrated to be the major site of metabolism in isolated liver perfusion studies in which both (1-14C)- and (2'-14C)-streptozotocin were quantitatively converted to the two major metabolites. The two major metabolites of (1-14C)-streptozotocin, whether produced in vivo or in vitro, were chromatographically homogenous with the two major metabolites formed from (2'-14C)-streptozotocin. Nicotinamide pretreatment had no apparent effect on the urinary excretion of streptozotocin and its metabolites.
The rat models of non-insulin dependent diabetes induced by neonatal streptozotocin
Diabete Metab.1989 Mar-Apr;15(2):61-75.PMID:2525491
This review is intended to describe the characteristics of the rat models of non-insulin-dependent diabetes induced by neonatal streptozotocin administration (n-STZ models), to sum-up the information so far collected and to highlight the potential of these models for diabetes research. The n-STZ models can now be recognized as adequate tools for the elucidation of the mechanisms leading to: 1) regeneration of the beta cells, 2) the functional "exhaustion" of the beta cells, 3) the emergence of defects in insulin action. They appear well-suited to study the effects of the modulating factors involved in the appearance and/or deterioration of non-insulin-dependent diabetes (obesity, gestation, content of the diet). They are potentially appropriate for investigations in diabetes pharmacotherapy.