Tezacitabine
(Synonyms: 替扎西他滨) 目录号 : GC64373
Tezacitabine 是一种具有细胞生长抑制和细胞毒性的抗代谢药，是一种核苷类似物。Tezacitabine 不可逆地抑制核糖核苷酸还原酶 (ribonucleotide reductase) 并干扰 DNA 复制和修复。Tezacitabine 有效诱导细胞凋亡 (apoptotic)，可用于白血病和实体瘤的研究。
Cas No.:130306-02-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Tezacitabine is a cytostatic and cytotoxic antimetabolite and a nucleoside analogue. Tezacitabine irreversibly inhibits the ribonucleotide reductase and interferes with DNA replication and repair. Tezacitabine effectively induces cells apoptotic. Tezacitabine has the potential for leukemias and solid tumors (carcinomas) treatment[1][2].
Tezacitabine (0.01-10 µM; 24 hours; CCRF-SB, KG-1, Jurkat, COLO-205, MCF-7 and PC-3 cells) treatment induces the G1 and S-phase leaky block of the cell cycle[1].Tezacitabine (0.01-10 µM; 24 hours; CCRF-SB, KG-1, Jurkat, COLO-205, MCF-7 and PC-3 cells) treatment apoptotic death of cells by the caspase 3/7 pathway in a concentration-dependent manner[1].Tezacitabine has strong cytostatic and cytotoxic properties. Cytotoxic effect of Tezacitabine reveals not only as apoptosis, but also as a change in protein metabolism[1].
Tezacitabine (100 mg/kg; intraperitoneal injection; daily; female nude mice) treatment inhibits tumor growth in HCT 116 tumor xenografts[2].
[1]. Janusz S Skierski, et al. Tezacitabine Blocks Tumor Cells in G1 and S Phases of the Cell Cycle and Induces Apoptotic Cell Death. Acta Pol Pharm. May-Jun 2005;62(3):195-205.
[2]. Pietro Taverna, et al. Tezacitabine Enhances the DNA-directed Effects of Fluoropyrimidines in Human Colon Cancer Cells and Tumor Xenografts. Biochem Pharmacol. 2007 Jan 1;73(1):44-55.
| Cas No. | 130306-02-4 | SDF | Download SDF |
| 别名 | 替扎西他滨 | ||
| 分子式 | C10H12FN3O4 | 分子量 | 257.22 |
| 溶解度 | DMSO : 200 mg/mL (777.54 mM; Need ultrasonic) | 储存条件 | -80°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.8877 mL | 19.4386 mL | 38.8772 mL |
| 5 mM | 0.7775 mL | 3.8877 mL | 7.7754 mL |
| 10 mM | 0.3888 mL | 1.9439 mL | 3.8877 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Tezacitabine Hoechst Marion Roussel
Curr Opin Investig Drugs 2000 Sep;1(1):135-40.PMID:11249589doi
Tezacitabine (MDL-101731, KW-2331, FMdC), an antimetabolite deoxycytidine analog, is an irreversible ribonucleotide reductase inhibitor and DNA chain terminator discovered by Hoechst Marion Roussel, now Aventis Pharma, and under development by Matrix and Kyowa as a potential treatment for solid tumors [117987,153697]. It is in phase II trials for colorectal and hematological cancer [333949,343071,353481] and was evaluated in a phase II trial for non-small cell lung cancer, for which enrollment was reported to have stopped [342009]; however, Tezacitabine continues to be explored for this indication [378351]. In February 1999, the first phase II trial patient was treated with Tezacitabine. A total of 30 patients with non-small cell lung cancer were expected to be enrolled by Matrix [316463]; however, in October 1999, Matrix closed enrollment in this trial (after 28 patients were enrolled); preliminary analysis of the evaluable patients did not show meaningful clinical activity with Tezacitabine as a stand-alone therapy in this indication at the dose and regimen tested [342009]. In May 1999, Matrix announced it would enroll up to 30 colorectal cancer patients for treatment in a phase II study [326017]. Despite closing enrollment for the NSCLC trial, as of October 1999, the phase II trial of Tezacitabine in colorectal cancer was continuing to accrue patients [342009]. In March 2000, a clinical trial was initiated at the University of Pennsylvania to study Tezacitabine administered intravenously in combination with cisplatin; a phase I trial studying the drug in combination with 5-FU at the Dana Farber Cancer Institute also commenced at that time [360590]. In May 1999, the results of four phase I trials were presented at the 35th Annual Meeting of the American Society of Clinical Oncology (ASCO). The studies enrolled 70 patients, 97% of whom had had previous chemotherapy and 46% of whom had failed three or more prior regimens. Groups of patients were given i.v. infusions of Tezacitabine in schedules ranging from once every 3 weeks to twice a week for 3 weeks at doses ranging from 16 to 630 mg/m2. The dose-escalation studies showed the compound to be well tolerated and indications of efficacy were observed in patients with various advanced solid tumors [325070,327102]. In September 1998, Matrix Pharmaceutical acquired worldwide rights to Tezacitabine except in Japan [299373]. Kyowa Hakko Kogyo has a license from HMR to develop Tezacitabine in Japan [195494]; in 1995, the company began phase I clinical trials in Japan for Tezacitabine administered orally [195494]. In 1996, this product was designated one of HMR's nine top priority products, serving an unmet medical need and addressing a potential market in excess of US $500 million per year [221118].
Tezacitabine enhances the DNA-directed effects of fluoropyrimidines in human colon cancer cells and tumor xenografts
Biochem Pharmacol 2007 Jan 1;73(1):44-55.PMID:17046720DOI:10.1016/j.bcp.2006.09.009.
Tezacitabine is a nucleoside analogue characterized by a dual mechanism of action. Following intracellular phosphorylation, the Tezacitabine diphosphate irreversibly inhibits ribonucleotide reductase, while the Tezacitabine triphosphate can be incorporated into DNA during replication or repair, resulting in DNA chain termination. In the present study we have investigated the effect of the combination of Tezacitabine and 5-fluorouracil (5-FU) or 5-fluoro-2'-deoxyuridine (FUdR) on HCT 116 human colon carcinoma cells and xenografts. We used response surface analysis (RSA) and clonogenic assay to evaluate combination effects of Tezacitabine and 5-FU. Tezacitabine is antagonistic when combined with 5-FU in the RSA assay and does not effect the clonogenicity of HCT 116 cells when compared with cells treated with 5-FU alone. However, when combined sequentially with FUdR, Tezacitabine leads to potentiation of cell killing in the clonogenic assay, additivity in the RSA assay, and increased apoptosis when compared to FUdR alone, suggesting that cytotoxicity of fluoropyrimidines such as FUdR that have more DNA-directed effects can be potentiated by Tezacitabine. We also report that oral administration of the fluoropyrimidine capecitabine, an oral prodrug of 5-FU, in combination with Tezacitabine shows statistically significant additivity in the HCT 116 xenograft model. This interaction may be explained by the finding that Tezacitabine elevates activity of thymidine phosphorylase (TP), the enzyme required for activation of the capecitabine prodrug in tumors. Our results provide evidence that Tezacitabine enhances the DNA-directed effects of fluoropyrimidines in human colon cancer cells and may modulate the antitumor activity of fluoropyrimidines.
Tezacitabine blocks tumor cells in G1 and S phases of the cell cycle and induces apoptotic cell death
Acta Pol Pharm 2005 May-Jun;62(3):195-205.PMID:16193812doi
Tezacitabine (FMdC) is a new cytostatic/cytotoxic agent widely investigated in clinical trials and on the cellular level. In a previous paper (3) we worked on human and murine leukemia (L-1210, HL-60, and MOLT-4) cells, and in this paper we investigated the influence of FMdC on the cell cycle and apoptosis in vitro of three other leukemias (CCRF-SB, KG-1, and Jurkat), and human solid tumor (carcinoma) cell lines (COLO-205, MCF-7, and PC-3). We found that FMdC induces the G1 (at concentrations higher than 10 nM). and S-phase (at low concentration) leaky block of the cell cycle. FMdC also effectively induces apoptotic death of cells by the caspase 3/7 pathway. We found also that FMdC induces intensive changes in the protein metabolism. These changes are correlated with the cell death.
Cytotoxic effects of cladribine and Tezacitabine toward HL-60
Acta Biochim Pol 2005;52(2):561-5.PMID:15933759doi
The aim of the study was to determine the relation between the cytotoxic and cytostatic effects of Tezacitabine and cladribine on a HL-60 cell line and the time of exposure of cells to these drugs. Cell viability and induction of apoptosis were assessed using flow cytometry methods. Apoptosis was confirmed by direct microscopic observation. Growth inhibition was examined by cell counting. After 24 h incubation Tezacitabine was equally or less toxic compared to cladribine. However, toxicity of Tezacitabine strongly rose after 48 h incubation leading to massive cell death at doses much lower than those of cladribine. Assessment of the effect of increased exposure time on the clinical efficacy of Tezacitabine is indicated.
Phase I dose-escalation study of Tezacitabine in combination with 5-fluorouracil in patients with advanced solid tumors
Cancer 2005 May 1;103(9):1925-31.PMID:15772958DOI:10.1002/cncr.21002.
Background: Tezacitabine [(E)-2'-deoxy-2'-(fluoromethylene) cytidine; FMdC] is a novel nucleoside analog with potent antiproliferative and antitumor activity in preclinical studies. A tolerable safety profile and clinical activity have been shown in Phase I and Phase II clinical studies. The purpose of the current open-label, Phase I dose-escalation trial was to evaluate the combination of Tezacitabine and 5-fluorouracil (5-FU) in the treatment of patients with advanced solid tumors. Methods: Twenty-four patients with a variety of advanced solid tumors for which there was no curative therapy were enrolled. Bolus infusion Tezacitabine was administered on Day 1 of a 14-day cycle at escalating doses of 150-350 mg/m(2), with continuous infusion 5-FU (CI 5-FU) given on Days 1-7 at a fixed dose of 200 mg/m(2) per day. Patients underwent objective tumor evaluation by radiologic methods or clinical examination at baseline and after every fourth treatment cycle. Results: The maximum tolerated dose of the combination therapy was determined to be Tezacitabine, 200 mg/m(2), with CI 5-FU, 200 mg/m(2) per day. The toxicities were manageable, the most notable being transient severe (National Cancer Institute Common Toxicity Criteria Grade 3 or 4) neutropenia in 23 patients (96%). Eleven (55%) of the 20 assessable patients had partial responses or stabilization of disease. The highest response rate was in patients with primary tumors of esophageal origin. Conclusions: Tezacitabine at a dose of 200 mg/m(2) in combination with CI 5-FU at a dose of 200 mg/m(2) per day was relatively well tolerated and had clinical activity in patients with advanced solid tumors, particularly in patients with esophageal and other gastrointestinal carcinomas.