Pyridazinediones deliver potent, stable, targeted and efficacious antibody-drug conjugates (ADCs) with a controlled loading of 4 drugs per antibody
Pyridazinediones deliver potent, stable, targeted and efficacious antibody-drug conjugates (ADCs) with a controlled loading of 4 drugs per antibody
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DOI：
10.1039/c7ra00788d
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发表时间：
2017-01-01
期刊：
影响因子：
3.9
通讯作者：
Chudasama, Vijay
中科院分区：
文献类型：
--
作者：
Robinson, Eifion;Nunes, Joao P. M.;Chudasama, Vijay
在本文中，我们报告了使用哒嗪二酮官能化曲妥珠单抗中的天然溶剂可及链间二硫键与单甲基奥瑞他汀E（MMAE）。这种缀合方法递送具有4.此外，我们证明了携带MMAE的ADC在体外和体内模型中都对癌细胞系具有强效、选择性和有效性。
Herein we report the use of pyridazinediones to functionalise the native solvent accessible interstrand disulfide bonds in trastuzumab with monomethyl auristatin E (MMAE). This method of conjugation delivers serum stable antibody-drug conjugates (ADCs) with a controlled drug loading of 4. Moreover, we demonstrate that the MMAE-bearing ADCs are potent, selective and efficacious against cancer cell lines in both in vitro and in vivo models.