產(chǎn)品描述: Dexrazoxane HCl (ADR-529,Totect, ICRF-187, Zinecard, Cardioxane)是一種胞內(nèi)鐵螯合劑,能夠減少氧自由基 的生成,是心臟保護(hù)劑。也是topoisomerase II的抑制劑 |
靶點(diǎn):
Topo II(Cell-free assay);Topoisomerase |
體外研究:
在大鼠心肌細(xì)胞中,Dexrazoxane (10 mM),臨床上限制蒽環(huán)類(lèi)藥物的心臟毒性,防止daunorubicin誘導(dǎo)的細(xì)胞凋亡,但不影響高濃度anthracycline誘導(dǎo)的壞死。在大鼠心肌細(xì)胞中,Dexrazoxane通過(guò)結(jié)合自由的鐵或松散結(jié)合的鐵絡(luò)合doxorubicin而發(fā)揮其心臟保護(hù)作用,從而防止或減少損害的細(xì)胞成分的位點(diǎn)特定的氧自由基產(chǎn)生。在H9C2心肌細(xì)胞中,Dexrazoxane特異抑制doxorubicin誘導(dǎo)的DNA損傷γ-H2AX信號(hào),但不影響camptothecin或過(guò)氧化氫。Dexrazoxane也誘導(dǎo)Top2beta的快速降解,這和doxorubicin誘導(dǎo)的DNA損傷的減少是相輔相成的。Dexrazoxane通過(guò)干擾Top2beta拮抗doxorubicin誘導(dǎo)的DNA損傷,表明Top2beta在doxorubicin心臟毒性中的作用。在H9C2心肌細(xì)胞中,Dexrazoxane在細(xì)胞內(nèi)水解成其活性形式并結(jié)合鐵,以防止形成超氧自由基,從而防止線(xiàn)粒體的破壞 |
體內(nèi)研究:
在B6D2F1小鼠中,Dexrazoxane和doxorubicin, daunorubicin或idarubicin聯(lián)用減少組織病變(傷口大小和時(shí)間曲線(xiàn))分別達(dá)96%,70%,87%。Dexrazoxane和doxorubicin, daunorubicin或idarubicin聯(lián)用導(dǎo)致傷口數(shù)量以及傷口的持續(xù)時(shí)間顯著減少 |
細(xì)胞實(shí)驗(yàn):
Cell lines: 新生大鼠心肌細(xì)胞 Concentrations: 30 μM Incubation Time: 3 h Method: 用dexrazoxane (DEX), sobuzoxane (SOB) 或 merbarone (MER) 預(yù)處理新生大鼠心肌細(xì)胞3小時(shí)后,加入anthracyclines daunorubicin或doxorubicin孵育3小時(shí),然后在anthracycline-free條件下孵育48小時(shí)或在hydrogen peroxide (H2O2)孵育48小時(shí) |
動(dòng)物實(shí)驗(yàn):
Animal Models: female B6D2FI Dosages: 62.5 mg/kg Administration: i.p. |
參考文獻(xiàn):
1. Sawyer DB, et al. Daunorubicin-induced apoptosis in rat cardiac myocytes is inhibited by dexrazoxane. Circ Res, 1999, 84(3), 257-265. 2. Hasinoff BB, et al. Chemical, biological and clinical aspects of dexrazoxane and other bisdioxopiperazines. Curr Med Chem, 1998, 5(1), 1-28. 3. Lyu YL, et al. Topoisomerase IIbeta mediated DNA double-strand breaks: implications in doxorubicin cardiotoxicity and prevention by dexrazoxane. Cancer Res, 2007, 67(18), 8839-8846. 4. Seifert CF, et al. Dexrazoxane in the prevention of doxorubicin-induced cardiotoxicity. Ann Pharmacother, 1994, 28(9), 1063-1072. 5. Langer SW, et al. Treatment of anthracycline extravasation with dexrazoxane. Clin Cancer Res, 2000, 6(9), 3680-3686. 6. Vavrova A, et al. Catalytic inhibitors of topoisomerase II differently modulate the toxicity of anthracyclines in cardiac and cancer cells. PLoS One. 2013, 8(10):e76676. 7. SW Langer, et al. Dexrazoxane is a potent and specific inhibitor of anthracycline induced subcutaneous lesions in mice. Annals of Oncology. 2001, 12: 405-4 |
溶解性:
Soluble in DMSO、H2O |
保存條件:
-20℃ |
配置溶液濃度參考:
|
1mg |
5mg |
10mg |
1 mM |
3.282 ml |
16.408 ml |
32.816 ml |
5 mM |
0.656 ml |
3.282 ml |
6.563 ml |
10 mM |
0.328 ml |
1.641 ml |
3.282 ml |
50 mM |
0.066 ml |
0.328 ml |
0.656 ml |
|
注意: |
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