國家衛生研究院 NHRI:Item 3990099045/14520
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    題名: Targeting the phosphatidylserine-immune checkpoint with a small-molecule maytansinoid conjugate
    作者: Lo, CF;Chiu, TY;Liu, YT;Pan, PY;Liu, KL;Hsu, CY;Fang, MY;Huang, YC;Yeh, TK;Hsu, TA;Chen, CT;Huang, LR;Tsou, LK
    貢獻者: Institute of Biotechnology and Pharmaceutical Research;Institute of Molecular and Genomic Medicine
    摘要: Ligand-targeting drug delivery systems have made significant strides for disease treatments with numerous clinical approvals in this era of precision medicine. Herein, we report a class of small molecule-based immune checkpoint-targeting maytansinoid conjugates. From the ligand targeting ability, pharmacokinetics profiling, in vivo anti-pancreatic cancer, triple-negative breast cancer, and sorafenib-resistant liver cancer efficacies with quantitative mRNA analysis of treated-tumor tissues, we demonstrated that conjugate 40a not only induced lasting regression of tumor growth, but it also rejuvenated the once immunosuppressive tumor microenvironment to an "inflamed hot tumor" with significant elevation of gene expressions that were not accessible in the vehicle-treated tumor. In turn, the immune checkpoint-targeting small molecule drug conjugate from this work represents a new pharmacodelivery strategy that can be expanded with combination therapy with existing immune-oncology treatment options.
    日期: 2022-10-13
    關聯: Journal of Medicinal Chemistry. 2022 Oct 13;65(19):12802-12824.
    Link to: http://dx.doi.org/10.1021/acs.jmedchem.2c00631
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-2623&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000862363500001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85139209463
    顯示於類別:[陳炯東] 期刊論文
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