Banoxantrone dihydrochloride (AQ4N dihydrochloride)
(Synonyms: AQ4N dihydrochloride) 目录号 : GC34085
Banoxantrone dihydrochloride (AQ4N dihydrochloride) 是一种缺氧活化拓扑异构酶 II 抑制剂，AQ4N 以非共价方式与 DNA 结合，促进缺氧和缺氧肿瘤细胞的抗肿瘤活性。
Cas No.:252979-56-9
Sample solution is provided at 25 µL, 10mM.
Banoxantrone dihydrochloride (AQ4N dihydrochloride) is an oxygen-depleted activated topoisomerase II inhibitor, AQ4N binds to DNA in a non-covalent manner and promotes antitumor activity of hypoxic and hypoxic tumor cells[1-4].
AQ4N(0-0.25 mM;24h) showed 8-fold higher cytotoxicity under hypoxia than normoxia in cultures of 9L rat gliosarcoma and H460 human non-small-cell lung carcinoma cells[5].
AQ4N(200 mg/kg; i.p.; 30 minutes before radiation) was combined with radiation, considerable DNA damage was detected in T50/80 tumors implanted in BDF mice after immediate excision[2,6].Activation of AQ4N cytotoxicity in mice requires extensive and prolonged tumor hypoxia[5]. AQ4N inhibited HMEC-1 cell contacts on Matrigel, HMEC-1 cell invasion, and sprouting in rat aorta explants. When AQ4N (20 mg/kg) was given in vivo for 5 days, microvessels disappeared in LNCaP tumors grown in a dorsal skin flap[7].
References:
[1]. Newell DR, Searle KM, Westwood NB, Burtles SS; Cancer Research UK Phase I/II Clinical Trials Committee. Professor Tom Connors and the development of novel cancer therapies by the Phase I/II Clinical Trials Committee of Cancer Research UK. Br J Cancer. 2003 Aug 4;89(3):437-54. doi: 10.1038/sj.bjc.6601106. PMID: 12888809; PMCID: PMC2394365.
[2]. Hejmadi MV, McKeown SR, et,al. DNA damage following combination of radiation with the bioreductive drug AQ4N: possible selective toxicity to oxic and hypoxic tumour cells. Br J Cancer. 1996 Feb;73(4):499-505. doi: 10.1038/bjc.1996.87. PMID: 8595165; PMCID: PMC2074454.
[3]. Patterson LH, McKeown SR, et,al. Enhancement of chemotherapy and radiotherapy of murine tumours by AQ4N, a bioreductively activated anti-tumour agent. Br J Cancer. 2000 Jun;82(12):1984-90. doi: 10.1054/bjoc.2000.1163. PMID: 10864207; PMCID: PMC2363261.
[4]. Patterson LH, McKeown SR. AQ4N: a new approach to hypoxia-activated cancer chemotherapy. Br J Cancer. 2000 Dec;83(12):1589-93. doi: 10.1054/bjoc.2000.1564. PMID: 11104551; PMCID: PMC2363465.
[5]. Manley E Jr, Waxman DJ. Impact of tumor blood flow modulation on tumor sensitivity to the bioreductive drug banoxantrone. J Pharmacol Exp Ther. 2013 Feb;344(2):368-77. doi: 10.1124/jpet.112.200089. Epub 2012 Nov 28. PMID: 23192656; PMCID: PMC3558827.
[6]. McKeown SR, Hejmadi MV, et,al. AQ4N: an alkylaminoanthraquinone N-oxide showing bioreductive potential and positive interaction with radiation in vivo. Br J Cancer. 1995 Jul;72(1):76-81. doi: 10.1038/bjc.1995.280. PMID: 7599069; PMCID: PMC2034137.
[7]. O'Rourke M, Ward C, et,al. Evaluation of the antiangiogenic potential of AQ4N. Clin Cancer Res. 2008 Mar 1;14(5):1502-9. doi: 10.1158/1078-0432.CCR-07-1262. PMID: 18316575.
Banoxantrone dihydrochloride (AQ4N dihydrochloride) 是一种缺氧活化拓扑异构酶 II 抑制剂，AQ4N 以非共价方式与 DNA 结合，促进缺氧和缺氧肿瘤细胞的抗肿瘤活性[1-4]。
AQ4N(0-0.25 mM;24h) 在 9L 大鼠神经胶质肉瘤和 H460 人非小细胞肺癌细胞培养物中表现出缺氧条件下比常氧条件下高 8 倍的细胞毒性[5]。
AQ4N （200 mg/kg；i.p.；放疗前 30 分钟）与放疗相结合，在立即切除后植入 BDF 小鼠的 T50/80 肿瘤中检测到相当大的 DNA 损伤 [2,6]。在小鼠中激活 AQ4N 细胞毒性需要广泛和长期肿瘤缺氧[5]。 AQ4N 抑制基质胶上的 HMEC-1 细胞接触、HMEC-1 细胞侵袭和大鼠主动脉外植体的发芽。体内给予 AQ4N (20 mg/kg) 5 天后，生长在背侧皮瓣的 LNCaP 肿瘤中微血管消失[7]。
| Cell experiment [1]: | |
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Cell lines |
9L rat gliosarcoma and H460 human non-small-cell lung carcinoma cells |
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Preparation Method |
Cells were treated with Banoxantrone dihydrochloride (AQ4N dihydrochloride) (0-0.25 mM) for 24 hours under normoxia or 0.1% O2. The culture medium was then changed to drug-free medium, and the cells were additionally cultured for 3 days under normoxia. Relative cell survival was determined by crystal violet staining of the cells remaining at the end of the experiment (A595 nm). |
|
Reaction Conditions |
0-0.25 mM;24h |
|
Applications |
Banoxantrone dihydrochloride showed 8-fold higher cytotoxicity under hypoxia than normoxia in cultures of 9L rat gliosarcoma and H460 human non-small-cell lung carcinoma cells. |
| Animal experiment [2]: | |
|
Animal models |
8-12 week old male BD2F1 mice |
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Preparation Method |
Tumor( poorly differentiated T50/80 murine mammary carcinoma) grafting in mice,AQ4N was administered as a single i.p. injection at a dose of 200 mg/kg. The drug was given 30 min before a single dose of X-irradiation of 12 Gy. Tumours were excised at a range of times following treatment and placed on ice. The tumor was enzymolysis into single cells and detected by comet assay. |
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Dosage form |
200 mg/kg; i.p.; 30 minutes before radiation |
|
Applications |
AQ4N was combined with radiation, considerable DNA damage was detected in T50/80 tumors implanted in BDF mice after immediate excision. |
|
References: [1]. Manley E Jr, Waxman DJ. Impact of tumor blood flow modulation on tumor sensitivity to the bioreductive drug banoxantrone. J Pharmacol Exp Ther. 2013 Feb;344(2):368-77. doi: 10.1124/jpet.112.200089. Epub 2012 Nov 28. PMID: 23192656; PMCID: PMC3558827. | |
| Cas No. | 252979-56-9 | SDF | |
| 别名 | AQ4N dihydrochloride | ||
| Canonical SMILES | O=C1C2=C(C(O)=CC=C2O)C(C3=C(NCC[N+](C)(C)[O-])C=CC(NCC[N+](C)(C)[O-])=C13)=O.Cl.Cl | ||
| 分子式 | C22H30Cl2N4O6 | 分子量 | 517.4 |
| 溶解度 | Water : 25 mg/mL (48.32 mM) | 储存条件 | Store at -20°C, protect from light, stored under nitrogen |
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.9327 mL | 9.6637 mL | 19.3274 mL |
| 5 mM | 0.3865 mL | 1.9327 mL | 3.8655 mL |
| 10 mM | 0.1933 mL | 0.9664 mL | 1.9327 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。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
