CAS: 1234480-50-2; 2-((2-Ethoxy-4-(4-Hydroxypiperidin-1-yl)Phenyl)Amino)-5,11-Dimethyl-5,11-Dihydro-6H-Benzo[e]Pyrimido[5,4-B][1,4]Diazepin-6-One

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    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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    1: Xiao H, Wang A, Shuai W, Qian Y, Wu C, Wang X, Yang P, Sun Q, Wang G, Ouyang L, Sun Q. A first-in-class selective inhibitor of ERK1/2 and ERK5 overcomes drug resistance with a single-molecule strategy. Signal Transduct Target Ther. 2025 Feb 20;10(1):70. doi: 10.1038/s41392-025-02169-z.
    2: Aoki-Utsubo C, Kameoka M, Deng L, Hanafi M, Dewi BE, Sudarmono P, Wakita T, Hotta H. Statins enhance extracellular release of hepatitis C virus particles through ERK5 activation. Microbiol Immunol. 2024 Oct;68(10):359-370. doi: 10.1111/1348-0421.13166. Epub 2024 Jul 29.
    226:335-342. doi: 10.1016/j.theriogenology.2024.06.028. Epub 2024 Jun 27. 194(8):1581-1591. doi: 10.1016/j.ajpath.2024.03.015. Epub 2024 May 3. 18(19):12386-12400. doi: 10.1021/acsnano.4c01518. Epub 2024 May 3. 39(1):2287990. doi: 10.1080/14756366.2023.2287990. Epub 2023 Dec 7.

    合成参考文献


    参考文献:10.1124/mol.119.115964
    摘要:Lee TD, Lee OW, Brimacombe KR, Chen L, Guha R, Lusvarghi S, Tebase BG, Klumpp-Thomas C, Robey RW, Ambudkar SV, Shen M, Gottesman MM, Hall MD. A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Molecular Pharmacology. 2019 Nov;96(5):629–40. doi: 10.1124/mol.119.115964.
    参考文献:10.1038/s41467-019-14083-4
    摘要:Tai F, Gong K, Song K, He Y, Shi J. Enhanced JunD/RSK3 signalling due to loss of BRD4/FOXD3/miR-548d-3p axis determines BET inhibition resistance. Nature Communications. 2020 Jan 14;11(1):258. doi: 10.1038/s41467-019-14083-4.
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