國家衛生研究院 NHRI:Item 3990099045/10556
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    題名: Targeting tumor associated phosphatidylserine with new zinc dipicolylamine-based drug conjugates
    作者: Liu, YW;Shia, KS;Wu, CH;Liu, KL;Yeh, YC;Lo, CF;Chen, CT;Chen, YY;Yeh, TK;Chen, WH;Jan, JJ;Huang, YC;Huang, CL;Fang, MY;Gray, BD;Pak, KY;Hsu, TA;Huang, KH;Tsou, LK
    貢獻者: Institute of Biotechnology and Pharmaceutical Research
    摘要: A series of zinc(II) dipicolylamine (ZnDPA)-based drug conjugates have been synthesized to probe the potential of phosphatidylserine (PS) as a new antigen for small molecule drug conjugate (SMDC) development. Using in vitro cytotoxicity and plasma stability studies, PS-binding assay, in vivo pharmacokinetic studies, and maximum tolerated dose profiles, we provided a roadmap and the key parameters required for the development of the ZnDPA based drug conjugate. In particular, conjugate 24 induced tumor regression in the COLO 205 xenograft model and exhibited a more potent antitumor effect with a 70% reduction of cytotoxic payload compared to that of the marketed irinotecan when dosed at the same regimen. In addition to the validation of PS as an effective pharmacodelivery target for SMDC, our work also provided the foundation that, if applicable, a variety of therapeutic agents could be conjugated in the same manner to treat other PS-associated diseases.
    日期: 2017-07
    關聯: Bioconjugate Chemistry. 2017 Jul;28(7):1878-1892.
    Link to: http://dx.doi.org/10.1021/acs.bioconjchem.7b00225
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1043-1802&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000406172600012
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85025124843
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