(EN) The invention relates to an intermediate (a combination of a connexon and a load) for preparing an antibody and a drug conjugate (ADC) and a preparation method and application thereof. Specifically, the combination of the connexon and the load has a structure shown as a formula I, the compound shown as the formula I can be applied to coupling of high-hydrophobicity compound loads such as paclitaxel (PTX') and the like which are not easy to couple, and the prepared ADC molecule has good hydrophilicity and thermal stability and can reach a relatively high drug-to-antibody ratio (DAR) value. According to the intermediate, the Trop-2 targeting ADC prepared by using the connexon represented by the formula I shows the strong in vitro drug effect in the low expression cell line in the Trop-2 compared to the Trop-2 targeting ADC with the effective loads of MMAE and SN38, and shows the strong tumor inhibition ability in the mouse in vivo xenotransplantation tumor model, and the bystander effect is proved. Experimental results show that the problem that the paclitaxel compound is used as an ADC effective load can be solved by utilizing the hydrophilic connexon, and ADC molecules which are expected to be used for treating various human cancers are obtained.
(ZH) 本发明涉及一种用于抗体与药物偶联体(ADC)制备的中间体(连接子与载荷组合)及其制备方法和应用。具体地，本发明的连接子与载荷组合具有式I结构，式I化合物可以应用于紫杉醇类(PTX')等不易被偶联的高疏水性化合物载荷的偶联，制备的ADC分子具有良好的亲水性和热稳定性，并且可以达到较高的药物与抗体比例(DAR)值。利用式I连接子制备的靶向Trop‑2的ADC在Trop‑2中低表达的细胞系中显示出了比有效载荷为MMAE和SN38的靶向Trop‑2的ADC更强的体外药效，并在小鼠体内异种移植瘤模型中显示出了较强的肿瘤抑制能力，且被证明具有“旁观者效应”。实验结果表明，通过利用这种亲水性连接子可以解决将紫杉醇类化合物用作ADC有效载荷的问题，并获得了有望用于治疗多种人类癌症的ADC分子。
