| 产品描述： | Banoxantrone dihydrochloride is a novel bioreductive agent that can be reduced to a stable, DNA-affinic compound AQ4, which is a potent topoisomerase II inhibitor. |
| 靶点： |
Topoisomerase II |
| 体外研究： |
Banoxantrone (AQ4N) can be reduced in a hypoxic environment to a stable DNA-affinic agent AQ4. AQ4, a potent topoisomerase II inhibitor, would be capable of damaging cells recruited into the cell cycle following radiation damage to the well-oxygenated cells of the tumor. Banoxantrone shows more than 8-fold higher cytotoxicity under hypoxia than normoxia in cultures of 9L rat gliosarcoma and H460 human non-small-cell lung carcinoma cells but not for 11 other human cancer cell lines. DT-diaphorase protein levels and banoxantrone chemosensitivity are poorly correlated across the cancer cell line panel, and banoxantrone chemosensitivity is not affected by DT-diaphorase inhibitors. Banoxantrone is a bis-N-oxide that is reduced via two sequential two-electron reductions to the tertiary amine, AQ4, which is a potent cytotoxic agent toward both aerobic and hypoxic cells. AQ4, but not AQ4N, intercalates in DNA with high affinity to generate a stable persistent complex that can inhibit topoisomerase II and cause DNA damage and cell death |
| 体内研究： |
Banoxantrone (200 mg/kg) significantly enhances the tumor growth delay caused by radiation. This occurred when radiation is administered both as a single dose (12 Gy) and in a multifraction regimen (5x3 Gy). A study of the scheduling of Banoxantrone (AQ4N) administration shows that there is a very long time period over which a maximal effect can be elicited (drug given 4 days before to 6 h after radiation). These results suggest that Banoxantrone has significant potential as a bioreductive drug. The activation of banoxantrone cytotoxicity in vivo requires tumor hypoxia that is more extensive or prolonged than can readily be achieved by vasodilation or by antiangiogenic drug treatment. Incorporation of banoxantrone into conventional chemoradiation protocols therefore targets both oxygenated and hypoxic regions of tumors, and potentially will increase the effectiveness of therapy. A single dose of 60 mg/kg banoxantrone enhances the response of RT112 (bladder) and Calu-6 (lung) xenografts to treatment with cisplatin and radiation therapy. Banoxantrone will increase the efficacy of chemoradiotherapy in preclinical models |
| 参考文献： |
1. Hejmadi MV, 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. 2. Manley E Jr, et al. Impact of tumor blood flow modulation on tumor sensitivity to the bioreductive drug banoxantrone. J Pharmacol Exp Ther. 2013 Feb;344(2):368-77. 3. Williams KJ, et al. In vivo activation of the hypoxia-targeted cytotoxin AQ4N in human tumor xenografts. Mol Cancer Ther. 2009 Dec;8(12):3266-75. |
| 溶解性： |
Soluble in DMSO、H2O |
| 保存条件： |
-80℃（运输条件：冰袋低温运输） |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
1.933 ml |
9.664 ml |
19.327 ml |
| 5 mM |
0.387 ml |
1.933 ml |
3.865 ml |
| 10 mM |
0.193 ml |
0.966 ml |
1.933 ml |
| 50 mM |
0.039 ml |
0.193 ml |
0.387 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京