Troxacitabine (BCH 4556)
(Synonyms: 4-氨基-1-[(2S)-2-(羟甲基)-1,3-二氧杂环戊-4-基]嘧啶-2-酮,BCH 4556; L-OddC; SPD 758) 目录号 : GC34184
Troxacitabine (BCH 4556) 是具有有效抗癌活性的核苷类似物。
Cas No.:145918-75-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Mice[3]Troxacitabine is administered i.v. to the animals at doses of 10 and 25 mg/kg on a daily 3 5 regimen. Gemcitabine is used as a positive control. The end points for the study included tumor growth inhibition (TGI), final weight, and the number of partial and complete tumor responses in the animals[3]. |
References: [1]. Gourdeau H, et al. Antitumor activity of troxacitabine (Troxatyl) against anthracycline-resistant human xenografts. Cancer Chemother Pharmacol. 2002 Dec;50(6):490-6. | |
Troxacitabine is nucleoside analog with potent anticancer activity.
Troxacitabine has shown cutotoxicity in cancer cell lines of hepatocellular (HepG2), prostate (PC3, DUI45), non-small cell lung (NCI-H460, NCr-322M) colon (HT29), renal (CAK-l, A498, RXF-393, SNI2-C) and pancreatic origin (Pnac-Ol, MiaPa Ca) with IC50s range from 15-35 μM[1][2].
Troxacitabine is highly active against the Panc-01 model, with TGI levels of 88.5% and 84.3% at the 10 and 25 mg/kg doses, respectively. The mean final tumor weights for animals given troxacitabine are also significantly smaller compared with vehicle controls. Troxacitabine has less activity against the MiaPaCa model[3]. Troxacitabine is very effective in human RCC tumor xenograft models, including CAM-i, A498, RXF-393, and SN12C carcinomas. Very good responses are ob served in animals bearing CAM-i, A498, and RXF-393 RCC tumors given i.p. doses of 10, 25, and 50 mg/kg twice a day for 5 days[2].
[1]. Gourdeau H, et al. Antitumor activity of troxacitabine (Troxatyl) against anthracycline-resistant human xenografts. Cancer Chemother Pharmacol. 2002 Dec;50(6):490-6. [2]. Kadhim SA, et al. Potent antitumor activity of a novel nucleoside analogue, BCH-4556 (beta-L-dioxolane-cytidine), in human renal cell carcinoma xenograft tumor models. Cancer Res. 1997 Nov 1;57(21):4803-10. [3]. Weitman S, et al. The new dioxolane, (-)-2'-deoxy-3'-oxacytidine (BCH-4556, troxacitabine), has activity againstpancreatic human tumor xenografts. Clin Cancer Res. 2000 Apr;6(4):1574-8.
| Cas No. | 145918-75-8 | SDF | |
| 别名 | 4-氨基-1-[(2S)-2-(羟甲基)-1,3-二氧杂环戊-4-基]嘧啶-2-酮,BCH 4556; L-OddC; SPD 758 | ||
| Canonical SMILES | O=C1N=C(N)C=CN1[C@H]2O[C@@H](CO)OC2 | ||
| 分子式 | C8H11N3O4 | 分子量 | 213.19 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°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 | 4.6907 mL | 23.4533 mL | 46.9065 mL |
| 5 mM | 0.9381 mL | 4.6907 mL | 9.3813 mL |
| 10 mM | 0.4691 mL | 2.3453 mL | 4.6907 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。
Troxacitabine: BCH 4556, SPD 758, Troxatyl
Drugs R D 2003;4(4):264-8.PMID:12848594DOI:10.2165/00126839-200304040-00010.
Troxacitabine [BCH 4556; SPD 758; Troxatyl] is a DNA synthesis inhibitor. This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. It is a member of a novel class of nucleoside analogues discovered by BioChem Pharma and is the first example of a synthetic L-nucleoside analogue to have shown anticancer activity in animal models. On 11 May 2001, BioChem Pharma was acquired by, and integrated into, Shire Pharmaceuticals Group. In February 2002 Shire announced that it intended to pursue development of Troxacitabine as a treatment for solid tumours. In addition, Shire indicated that it would pursue the drug's development for acute myeloid leukaemia. In March 1999, phase II trials were initiated to investigate the efficacy and tolerability of Troxacitabine in a variety of solid tumours including pancreas, prostate, colorectal, renal and non-small cell lung cancers and melanoma. The trials were conducted throughout North America and were closed to patient accrual in 2000. Two phase I combination chemotherapy trials in solid tumours (one with cisplatin and another with paclitaxel) have been initiated. One of these trials is in patients with pancreatic cancer. A phase III trial in patients with pancreatic cancer is expected to begin during the second or third quarter of 2003. In addition, further clinical development was initiated in May 2000, in the form of a combination chemotherapy trial in patients with acute leukaemia. A phase II trial in patients with acute myeloid leukaemia (AML) and chronic myeloid leukaemia-blast phase (CML-BP) has reported that Troxacitabine demonstrated significant activity in these cancers. However, Shire indicated that no further development for CML-BP will be conducted. The company indicated that it would focus future development in the haematological malignancy area on AML and has initiated an exploratory phase III trial of Troxacitabine in previously untreated patients with poor prognosis AML. The study will compare Troxacitabine in combination with either cytarabine or idarubicin, with a control drug regimen. The aim is to identify the most promising treatment regimens in a relatively small number of patients before commencing the larger pivotal trial. A pivotal phase III trial is expected to begin in the first half of 2003. In September 2002, Shire Pharmaceuticals forecast Troxatyl to reach peak sales of $US100-200 million, for the indications of pancreatic cancer and myeloid leukaemia.
Troxacitabine in leukemia
Hematology 2006 Oct;11(5):321-9.PMID:17607581DOI:10.1080/10245330601027316.
Troxacitabine (Troxatyl; BCH-4556; (-)-2'-deoxy-3'-oxacytadine) is the first synthetic l-nucleoside enantiomer to demonstrate broad spectrum cytotoxic activity. It was obtained by exchanging the sulphur endocyclic atom with oxygen in the structure of lamivudine, following the discovery that this agent had cytotoxic, as well as anti-viral activity. The unique "unnatural" stereochemistry of Troxacitabine has produced impressive cytotoxic potency against a wide range of malignancies in the laboratory which led to its selection for clinical development. The initial trials with Troxacitabine have established its efficacy in both solid and haematological malignancies, including those resistant to ara-C (cytarabine). This review will consider Troxacitabine in terms of its pharmacology, mode of action, pharmacokinetics, toxicities, and clinical efficacy.
Comparative study of a novel nucleoside analogue (Troxatyl, Troxacitabine, BCH-4556) and AraC against leukemic human tumor xenografts expressing high or low cytidine deaminase activity
Cancer Chemother Pharmacol 2001 Mar;47(3):236-40.PMID:11320667DOI:10.1007/s002800000223.
Purpose: Troxacitabine (beta-L-dioxolane cytidine, BCH-4556; Troxatyl, BioChem Pharma Inc.) is a novel nucleoside analogue, which in experiments demonstrated potent antitumor activity against both leukemias and solid tumors. Since Troxacitabine is a cytidine nucleoside analogue like AraC (1-beta-D-arabinofuranosylcytosine), which is currently used in the treatment of acute myelogenous leukemia, we compared the in vivo antileukemic activity of Troxacitabine with that of AraC in human leukemia xenograft models. Methods: The antiproliferative activity of Troxacitabine and AraC was analyzed on hemapoietic cell lines by use of a thymidine incorporation assay. For in vivo studies, we compared Troxacitabine with AraC by using equitotoxic schedules of the two nucleosides optimized for therapeutic activity. The antileukemic activity of both drugs was evaluated by measurement of their effect on the percent increased lifespan. Results: AraC had good in vitro antiproliferative activity (IC50 = 14 nM) but was ineffective in vivo against the HL60 promyelocyte leukemia cell line (treated vs control, T/C = 105%). Troxacitabine, which in contrast to AraC is not a substrate for cytidine deaminase, showed potent in vitro and in vivo activity in the same model (IC50 = 53 nM and T/C = 272% to 422%). The poor in vivo activity of AraC against HL60 leukemia cells could be due to the high cytidine deaminase (CDA; EC 3.5.4.5) activity in this cell line. This hypothesis was tested with CCRF-CEM T-lymphoblastoid leukemia cells which have undetectable levels of CDA activity. Short-term exposure of these leukemia cell lines to both drugs indicated that AraC was indeed significantly more effective in the CCRF-CEM cell line than in HL60. In contrast, the antiproliferative activity of Troxacitabine was similar for both cell lines. These observations were extended to in vivo studies. Mice bearing CCRF-CEM tumor xenografts were treated with AraC and Troxacitabine. In this model, T/C values were comparable for both drugs and ranged from 138% to 157%. Conclusions: Our findings indicate that Troxacitabine is likely to be effective not only against solid tumors with high CDA activity but also in leukemias which have developed resistance to AraC due to increased CDA levels; this suggests that Troxacitabine is a promising agent for the treatment of cancer. Indeed, significant antileukemic activity has been observed with Troxacitabine in a phase I clinical trial in patients with primary refractory or relapsed acute myeloid leukemias (AML).
Troxacitabine in acute leukemia
Hematology 2007 Jun;12(3):219-27.PMID:17558697DOI:10.1080/10245330701406881.
Troxacitabine (Troxatyl; BCH-4556; (-)-2'-deoxy-3'-oxacytadine) is the first synthetic l-nucleoside enantiomer to demonstrate broad spectrum cytotoxic activity. It was obtained by exchanging the sulphur endocyclic atom with oxygen in the structure of lamivudine, following the discovery that this agent had cytotoxic, as well as anti-viral activity. The unique "unnatural" stereochemistry of Troxacitabine has produced impressive cytotoxic potency against a wide range of malignancies in the laboratory which led to its selection for clinical development. The initial trials with Troxacitabine have established its efficacy in both solid and haematological malignancies, including those resistant to ara-C (cytarabine). This review will consider Troxacitabine in terms of its pharmacology, mode of action, pharmacokinetics, tolerability and clinical efficacy.
Phase II study of Troxacitabine (BCH-4556) in patients with advanced non-small-cell lung cancer
Lung 2005 Jul-Aug;183(4):265-72.PMID:16211462DOI:10.1007/s00408-004-2539-7.
Troxacitabine. a promising new L-nucleoside, inhibits DNA polymerase and leads to complete DNA chain termination. The National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) conducted a phase II study to assess the efficacy and toxicity of Troxacitabine in untreated patients with advanced non-small-cell lung cancer (NSCLC). Previously untreated patients were eligible if they had inoperable stage IIIB or IV NSCLC, ECOG PS < or = 2, adequate hematology and biochemistry, and at least one bidimensionally measurable lesion. Patients with prior malignancy or brain metastases were excluded. Troxacitabine (10 mg/m(2)) was administered intravenously over 30 minutes every 3 weeks. Between June 1999 and May 2000, 17 eligible patients received treatment. Patient characteristics included: median age 64 years; female 41%; stage IV (94%); PS 0 (12%), 1 (59%), and 2 (29 %), 3 or more disease sites (59%). In 17 patients, there were 8 stable disease, 9 disease progression, and no objective responses. Median duration of stable disease was 3.6 months (range = 2.0-7.1). A total of 56 cycles were administered (median = 3), and 88% of patients received 90% or more of the planned dose intensity. The majority (82%) of patients experienced skin rash. Hematologic and biochemical toxicities, grade 3/4 (%) were: granulocytopenia (41), anemia (12), thrombocytopenia (6), and hyperglycemia (6). Troxacitabine appears to have little activity in NSCLC in the dose and schedule tested.