CAS: 467214-21-7; (4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-((2-(Dimethylamino)Ethyl)Amino)-13-Hydroxy-8,14-Dimethoxy-4,10,12,16-Tetramethyl-3,20,22-Trioxo-2-Azabicyclo[16.3.1]Docosa-1(21),4,6,10,18-Pentaen-9-Yl Carbamate Hydrochloride

该化合物是合成的炭疽抗生素,是热冲击蛋白90(Hsp90)的强大抑制剂,对许多肿瘤患者蛋白的稳定性和功能至关重要.该化合物显示与Hsp90高度结合,干扰其亚麻黄碱活动,导致癌症细胞扩散和存活过程中的客户蛋白退化.盐酸盐形式提高了溶性,提高了生物利用率,使之适合临床前和研究应用.甲酸乙醚在研究Hsp90在肿瘤学,...

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合成工艺路线路线简述

    📜N,N-二甲基乙二胺,丙烯胺 反应生成 阿螺旋霉素盐酸盐
    参考文献:Bioorg. Med. Chem. 2004,12,5317-5329
    标题:Bioorg. Med. Chem. 2004,12,5317-5329

    海关参考信息

    专利信息


    专利号:US-11285169-B2
    优先权日:2013-03-13
    标题 :Methods for modulating chemotherapeutic cytotoxicity
    发明人:ROBERTS DAVID D; SOTO PANTOJA DAVID R
    权利人:US HEALTH
    摘要:Methods of reducing cytotoxicity of a chemotherapeutic agent to non-cancer cells by administering to a subject with cancer an effective amount of an agent that inhibits CD47 signaling and a DNA damaging agent, such as an anthracycline, topoisomerase inhibitor, or nucleotide synthesis inhibitor, are provided. Example disclosed methods reduce cardiotoxicity. In one example, the methods include administering to a subject with cancer an effective amount of a CD47 antisense morpholino oligonucleotide and an anthracycline such as doxorubicin. Methods of increasing cytotoxicity of a chemotherapeutic agent in cancer cells by administering to a subject with a tumor an effective amount of an agent that inhibits CD47 signaling and a DNA damaging agent such as an anthracycline, topoisomerase inhibitor, or nucleotide synthesis inhibitor, are also provided. In some embodiments, the inhibitor of CD47 signaling is administered to the subject before, during, or after the administration of the DNA damaging agent.

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    ✅ COA系统入驻 | 共享模式

    主要参考文献


    1: Hu ZY, Lu J, Zhao Y. A physiologically based pharmacokinetic model of alvespimycin in mice and extrapolation to rats and humans. Br J Pharmacol. 2014 Jun;171(11):2778-89. doi: 10.1111/bph.12609.
    2: Hu Y, Bobb D, He J, Hill DA, Dome JS. The HSP90 inhibitor alvespimycin enhances the potency of telomerase inhibition by imetelstat in human osteosarcoma. Cancer Biol Ther. 2015;16(6):949-57. doi: 10.1080/15384047.2015.1040964. Epub 2015 Apr 28.
    3: Gao L, Zhao G, Fang JS, Yuan TY, Liu AL, Du GH. Discovery of the neuroprotective effects of alvespimycin by computational prioritization of potential anti-Parkinson agents. FEBS J. 2014 Feb;281(4):1110-22. doi: 10.1111/febs.12672. Epub 2014 Jan 9. doi: 10.1038/ng.3252. Epub 2015 Mar 30.

    合成参考文献


    参考文献:10.1016/j.ejmech.2017.04.074
    摘要:Wang L, Li L, Zhou Z, Jiang Z, You Q, Xu X. Structure-based virtual screening and optimization of modulators targeting Hsp90-Cdc37 interaction. European Journal of Medicinal Chemistry. 2017 Aug;136():63–73. doi: 10.1016/j.ejmech.2017.04.074.
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