streptozotocin | 1192476-74-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: streptozotocin
• 英文别名: streptozocin；Streptozotocin;U 9889；1-methyl-1-nitroso-3-[2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]urea
• CAS: 1192476-74-6
• 化学式: C₈H₁₅N₃O₇
• 分子量: 265.223
• InChiKey: ZSJLQEPLLKMAKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  152
• 氢给体数：
  5
• 氢受体数：
  8

ADMET

代谢

使用放射性碳-14标记链脲佐菌素的研究表明，在大鼠体内，链脲佐菌素会迅速代谢...产生源自甲基脲基侧链的代谢物。/SRP: 重氮甲烷/

STUDIES WITH STREPTOZOTOCIN LABELLED WITH (14)C IN DIFFERENT POSITIONS INDICATE THAT ITS RAPID METABOLISM IN RAT ... RESULTS IN METABOLITE DERIVED FROM METHYL BEARING NITROSOUREIDO SIDECHAIN. /SRP: DIAZOMETHANE/

来源:Hazardous Substances Data Bank (HSDB)

代谢

在老鼠尿液中检测到五种尿液代谢物；其中两种是抗生素的α和β-异构体。

/IN MICE URINE/ FIVE URINARY METABOLITES WERE DETECTED; 2 OF THEM WERE THE ALPHA AND BETA-ANOMERS OF THE ANTIBIOTIC.

来源:Hazardous Substances Data Bank (HSDB)

代谢

链脲佐菌素及其代谢物有一个短暂的分布期（t1/2 6分钟），随后可能有两个消除期，代表活性代谢物（t1/2 beta 3.5小时，t1/2 gamma 40小时）。

Streptozocin and metabolites have a short distribution phase (t1/2 6 min) followed by possibly two elimination phases representing active metabolites (t1/2 beta 3.5 hr, t1/2 gamma 40 hr).

来源:Hazardous Substances Data Bank (HSDB)

代谢

链脲佐菌素口服不活性。静脉给药后，它迅速从血浆中被清除，三小时后无法检测到。代谢物在血浆中可以检测到长达24小时。药物在某些组织中浓缩；肝脏和肾脏含有最高水平，胰腺也浓缩链脲佐菌素。原药和代谢物通过肾脏迅速消除；60%至70%的剂量在四小时内通过尿液回收。只有10%至20%的排泄剂量是原药。

Streptozocin is not orally active. After intravenous administration, it is rapidly cleared from plasma and is undetectable after three hours. Metabolites are detected in plasma for up to 24 hours. The drug concentrates in certain tissues; the liver and kidneys contain the highest levels, and pancreas also concentrates streptozocin. Parent drug and metabolites are eliminated rapidly by the kidney; 60% to 70% of a dose is recovered in urine within four hours. Only 10% to 20% of an excreted dose is parent drug.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 肝毒性

血清转氨酶升高发生在多达三分之二的使用链脲佐菌素治疗的病人中，但异常通常是轻微的、暂时的，并且不伴随症状或黄疸。每日剂量和高剂量的链脲佐菌素更常见肝毒性，但高剂量时，肾脏和血液毒性通常比肝脏损伤更为突出。已有两例报告称，在接受链脲佐菌素治疗的患者中出现了快速进展且致命的急性肝衰竭。在一个案例中，没有给予其他化疗，在另一个案例中，患者同时接受了氟尿嘧啶治疗，并在5天治疗结束时出现了发热、无尿、急性肝炎[ALT 1280，胆红素 11.9，凝血酶原指数 10%，嗜酸性粒细胞 2600/µL]。相比之下，没有已发表的个案报告将链脲佐菌素归因于自限性临床明显的肝损伤，但由于胰腺胰岛细胞癌和神经内分泌肿瘤较为罕见，链脲佐菌素的使用受到了限制。

Serum aminotransferase elevations occur in up to two-thirds of patients treated with streptozocin, but the abnormalities are generally mild, transient and not associated with symptoms or jaundice. Hepatotoxicity is more common with daily dosing and high doses of streptozocin, but with higher doses renal and hematologic toxicities usually overshadow hepatic injury. There have been two reports of rapidly progressive and fatal acute liver failure in patients treated with streptozocin. In one instance, no other chemotherapy was given, in another fluorouracil was coadministered and the patient presented with fever, anuria, acute hepatitis [ALT 1280, bilirubin 11.9, prothrombin index 10%, eosinophils 2600/ µL] at the end of a 5 day course of treatment. In contrast, there have been no individual published case reports of self-limited clinically apparent liver injury attributed to streptozocin, but it has had limited use, as pancreatic islet cell carcinoma and neuroendocrine tumors are rare.

来源:LiverTox

毒理性

• 致癌性证据

美国环保局健康与环境评估办公室的人类健康评估小组对链脲佐菌素进行了致癌性评估。根据他们的分析，链脲佐菌素的证据权重为B2组，这是基于动物实验中的充分证据。目前没有关于人类的数据。作为B2组化学物质，链脲佐菌素被认为可能对人类具有致癌性。

The Human Health Assessment Group in EPA's Office of Health and Environmental Assessment has evaluated streptozotocin for carcinogenicity. According to their analysis, the weight-of-evidence for streptozotocin is group B2, which is based on sufficient evidence in animals. No data are available in humans. As a group B2 chemical, streptozotocin is considered probably carcinogenic to humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

没有关于人类的数据。有充分的证据表明对动物具有致癌性。总体评估：2B组：该物质可能对人类具有致癌性。

No data are available in humans. Sufficient evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 2B: The agent is possibly carcinogenic to humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

链脲佐菌素：合理预期为人类致癌物。

Streptozotocin: reasonably anticipated to be a human carcinogen.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌剂：链脲佐菌素

IARC Carcinogenic Agent:Streptozotocin

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

在所有这些物种中（小鼠、大鼠、猫、猴子和狗），通过静脉注射给予链脲佐菌素（STZ）...在肝脏和肾脏中显著浓缩；例如，在狗中...在肝脏中保留了许多小时后...在血液中不再能检测到。

IN ALL THESE SPECIES /MICE, RATS, CATS, MONKEYS & DOGS/ STR /STREPTOZOTOCIN/ GIVEN PARENTERALLY ... MARKEDLY CONCENTRATED IN LIVER & KIDNEY; FOR EXAMPLE, IN DOGS ... RETAINED IN LIVER FOR MANY HR AFTER ... NO LONGER ... DETECTED IN BLOOD .

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

链脲佐菌素...在小鼠中从胃肠道很好地被吸收，但在猴子中吸收较差，在狗中几乎不被吸收。

STREPTOZOTOCIN ... WELL ABSORBED FROM GI TRACT IN MICE, BUT ABSORPTION WAS POOR IN MONKEYS & NEGLIGIBLE IN DOGS.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

(14)C标记的链脲佐菌素通过静脉注射给药后，在大鼠血液中迅速清除，10分钟后剩余量不到1%。

(14)C-LABELLED STREPTOZOTOCIN GIVEN BY IV INJECTION WAS RAPIDLY CLEARED FROM BLOOD OF RATS, SO THAT LESS THAN 1% REMAINED AFTER 10 MINUTES.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

链脲佐菌素（NSC-85998）在处理过的小鼠尿液中迅速排出；4小时尿液中的注射剂量有72%。检测到五种尿液代谢物...。

STREPTOZOTOCIN (NSC-85998) WAS RAPIDLY EXCRETED IN URINE OF TREATED MICE; 72% OF AN INJECTED DOSE IN THE 4-HR URINE. FIVE URINARY METABOLITES WERE DETECTED ... .

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在动物中，链脲佐菌素通过腹腔内或静脉给药后，药物及其代谢物迅速分布，主要进入肝脏、肾脏、肠道和胰腺，较低浓度的分布到骨骼肌、脾脏、肺、心脏和胸腺。药物或其代谢物在肝脏、肾脏、肠道和胰腺中的浓度始终高于血浆。链脲佐菌素在动物或人类中似乎不会穿过血脑屏障；然而，在人类中，链脲佐菌素的代谢物容易分布到脑脊液（CSF）中。在猴子中，药物容易穿过胎盘。

Following intraperitoneal or IV administration of streptozocin in animals, the drug and its metabolites are rapidly distributed mainly into the liver, kidneys, intestine, and pancreas, with lower concentrations being distributed into skeletal muscle, spleen, lungs, heart, and thymus. Concentrations of the drug or its metabolites in the liver, kidneys, intestine, and pancreas are consistently higher than those in plasma. Streptozocin does not appear to cross the blood-brain barrier in animals or humans; however, in humans, metabolites of streptozocin readily distribute into CSF. ... The drug readily crosses the placenta in monkeys.

来源:Hazardous Substances Data Bank (HSDB)

文献信息

• Materials and methods for suppressing and/or treating bacterial infections and related symptoms
  申请人：Indiana University Research and Technology Corporation

  公开号：US10933075B2

  公开（公告）日：2021-03-02

  Various aspects and embodiments disclosed herein relate generally to the modelling, treatment, reducing resistence to the treatment, prevention, and diagnosis of diseases/symptoms induced by infectious bacteria. Embodiments include methods of treating a bacterial infection, comprising the steps of: providing to a patient diagnosed with staphylococcal infection at least one therapeutically effective dose of a compound having an anti-virulence effect.

  本文公开的各种方面和实施方案一般涉及由传染性细菌诱发的疾病/症状的建模、治疗、降低对治疗的抵抗力、预防和诊断。实施方案包括治疗细菌感染的方法，包括以下步骤：向诊断为葡萄球菌感染的患者提供至少一种治疗有效剂量的具有抗病毒作用的化合物。
• Three-dimensional vascular network assembly from induced pluripotent stem cells
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US11332717B2

  公开（公告）日：2022-05-17

  Early vascular cells (EVCs), including endothelial cells and pericytes, are generated from hiPSCs. Unlike the isolated endothelial progenitor cells, the differentiated ECs mature and are functional. When encapsulated in synthetic hydrogel, EVCs respond to matrix cues and self-assembled to form three-dimensional EVCs. Moreover, these EVCs respond to hypoxic microenvironment and undergo vasculogenesis to form complex 3D networks.

  早期血管细胞（EVC），包括内皮细胞和周细胞，由 hiPSCs 生成。与分离的内皮祖细胞不同，分化后的EVC成熟并具有功能。当被包裹在合成水凝胶中时，EVC 对基质线索做出反应，并自我组装形成三维 EVC。此外，这些EVC还能对缺氧微环境做出反应，进行血管生成，形成复杂的三维网络。
• THREE-DIMENSIONAL VASCULAR NETWORK ASSEMBLY FROM INDUCED PLURIPOTENT STEM CELLS
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US20180216063A1

  公开（公告）日：2018-08-02

  Early vascular cells (EVCs), including endothelial cells and pericytes, are generated from hiPSCs. Unlike the isolated endothelial progenitor cells, the differentiated ECs mature and are functional. When encapsulated in synthetic hydrogel, EVCs respond to matrix cues and self-assembled to form three-dimensional EVCs. Moreover, these EVCs respond to hypoxic microenvironment and undergo vasculogenesis to form complex 3D networks.
• MATERIALS AND METHODS FOR SUPPRESSING AND/OR TREATING BACTERIAL INFECTIONS AND RELATED SYMPTOMS
  申请人：Indiana University Research and Technology Corporation

  公开号：US20190038648A1

  公开（公告）日：2019-02-07

  Various aspects and embodiments disclosed herein relate generally to the modelling, treatment, reducing resistence to the treatment, prevention, and diagnosis of diseases/symptoms induced by infectious bacteria. Embodiments include methods of treating a bacterial infection, comprising the steps of: providing to a patient diagnosed with staphylococcal infection at least one therapeutically effective dose of a compound having an anti-virulence effect.
• COMPOSITIONS AND METHODS FOR USE OF EFLORNITHINE AND DERIVATIVES AND ANALOGS THEREOF TO TREAT CANCERS, INCLUDING GLIOMAS
  申请人：Orbus Therapeutics, Inc.

  公开号：US20190133985A1

  公开（公告）日：2019-05-09

  Eflornithine is an agent that can be used to treat glioma, especially glioma of WHO Grade II or Grade III such as anaplastic glioma. Eflornithine can suppress or prevent mutations in glioma which can cause the glioma to progress to a higher grade. Compositions and methods can include eflornithine or a derivative or analog of eflornithine, together with other agents such as conventional anti-neoplastic agents for treatment of glioma, inhibitors of polyamine transport, polyamine analogs, or S-adenosylmethionine decarboxylase inhibitors. Eflornithine or derivatives or analogs thereof can also be used to treat a range of non-glioma malignancies, including both malignancies of the central nervous system and other malignancies.