Tivdak®、Aidixi®、Lumoxiti®、Zynlonta®、Enhertu®均使用组织蛋白酶B裂解的多肽Linker,其中对氨基苄基氨基甲酸酯(PABC)用作自降解间隔子,其在蛋白水解后自发进行1,6-消除,释放Payload、CO2和氮杂醌甲基化物(图4);PABC保持独立于Payload的酶活性,...
Chemical Linkers in Antibody–Drug Conjugates aims to shine a detailed light on the various key attributes of chemical linkers in ADCs, for drug-to-antibody ratio, for stability, for release mechanism of payload, for pharmacokinetics,...
最近的临床前实验中证明了四嗪-TCO对的“click and release”方法的可行性[22]。 展望 合适的Linker化学是ADC安全有效的重要保障。虽然不可裂解Linker的例子也有很多,但由于游离态Payload的细胞毒性以及旁观者效应的重要性,可裂解Linker是大多数ADC药物的首选。可酸裂解的Linker最初很有前景,但高毒性Payload所要求的...
This has resulted in fewer side effects as these antibodies selectively bind tumor cells and predominantly drive the therapeutic mechanism of action in these cells. In contrast, cells that do not express the target will not bind the antibody and therefore, will not be affected. However, the draw...
aims to shine a detailed light on the various key attributes of chemical linkers in ADCs, for drug-to-antibody ratio, for stability, for release mechanism of payload, for pharmacokinetics, for stability determination, and for efficacy and safety. Ideal for postgraduate students and active researche...
The TMALIN platform is featured as a high hydrophilicity linker-payload, remarkable stability in circulation, coupled with an efficient payload release mechanism which is achieved through the cleavage both extracellularly in the tumor microenvironment and intracellularly within lysosomes. A site-specific ...
ADCs药物的靶向性来自其中抗体部分(antibody),毒性大部分来自小分子化药毒物部分(payload),抗体部分也可以自带毒性(ADCC与CDC)。抗体部分与毒素部分通过连接物(linker)互相连接。抗体部分与肿瘤细胞表面的靶向抗原结合(binding)后,肿瘤细胞会将ADC内吞(endocytosis)。之后ADC药物会在溶酶体中分解(lysosomal degradation),释...
In theory, ADCs can be employed to counter the impact of platinum resistance in ovarian cancer, particularly when PROC patients have a pro-apoptotic mechanism for the cytotoxic payload through DNA repair pathway damage. The linker in an ADC is a critical component that bridges the monoclonal ...
Traditionally, the payloads like monomethyl auristatin E (MMAE) have been restricted in their use due to severe side effects and a lack of selectivity. However, in ADCs, these payloads exhibit a formidable anti-tumor capability [30]. Another critical mechanism of platinum resistance in ovarian ...
ADCs药物的靶向性来自其中抗体部分(antibody),毒性大部分来自小分子化药毒物部分(payload),抗体部分也可以自带毒性(ADCC与CDC)。抗体部分与毒素部分通过连接物(linker)互相连接。抗体部分与肿瘤细胞表面的靶向抗原结合(binding)后,肿瘤细胞会将ADC内吞(endocytosis)。之后ADC药物会在溶酶体中分解(lysosomal degradation),释...