Broadpharm提供可切割和不可切割Linker
antibody-drug conjugates (adcs) are composed of a drug (payload) and antibody (mabs) that are bound using linkages that are specifically designed to deliver the payload to the intended target environment. adcs are designed to sparing healthy cells by targeting specific cancer types.
this article expands upon the linker information in the adc linker technology in 2021 article. specifically, the cleavable and non-cleavable categories of adc linkers. cleavable linkers use inherent properties of tumor cells for selective release of payloads from the adcs. there are three commonly used mechanisms for cleavable linkers; protease-sensitive peptide linkers, acid sensitive hydrazone linkers, and glutathione-sensitive disulfide linkers.
protease-sensitive cleavable linkers use the dominant proteases found in tumor cell lysosomes for recognition and cleavage of a specific peptide sequence in the linker. a commonly used adc linker makes use of a valine-citrulline (vc) dipeptide, first discovered by dubowchik et al., as an intracellular cleavage mechanism by cathepsin b.
figure 1. adcetris with enzymatically cleavable val-cit linkage.acid-sensitive linkers use a lower ph in the endosomal (ph = 5-6) and lysosomal (ph = 4.8) compartments, in contrast to cytosol (ph = 7.4) to trigger hydrolysis of acid labile groups within a linker such as hydrazone.
glutathione-sensitive linkers use higher concentrations of intracellular glutathione that in the plasma. this causes disulfide bridges to release the payload upon reduction by glutathione.
cleavable linkers may also help with destroying cancer cell adjacent to their targets through a process referred to as bystander effect. the bystander effect occurs when the payload is released near the targeted cancer cell, or a payload diffuses out of one cancer cell and then is absorbed by a second cancer cell.
non-cleavable linkers only degrade when the anti-body degrades. release of the payload occurs mainly in the lysosome after internalization of the adc and degradation of both the antibody and linker. this may be an advantage since it could lead to a lower risk of systemic toxicity. figure 2 shows an example of kadcyla, which uses smcc crosslinker as the non-cleavable linker.
figure 2. kadcyla, shown with the linker in green and the payload in orange, was designed with a non-cleavable linkage.broadpharm offers a wide array of different adc linkers, peg linkers to empower our customer's advanced research worldwide. these compounds feature great aqueous solubility, smart choice of peg length, and a broad selection of functional groups to choose from.
journal reference:1.editorial team, fda grants accelerated approval for sacituzumab govitecan in metastatic triple-negative breast cancer, adc review (2020)
2.fda press release, fda grants accelerated approval to loncastuximab tesirine-lpyl for large b-cell lymphoma, (2021)
3.staudacher, brown, antibody drug conjugates and bystander killing: is antigen-dependent internalisation required?, br j cancer 117, (2017): 1736-1742
订购咨询靶点科技（北京）有限公司
制作牛肉膏蛋白胨培养基配方图文过程（二）
宏伟无人值守称重系统 朝阳10T地磅（开原20吨地磅）明山便携式汽车衡
关于如何选择色谱样品瓶
控温电热板的操作过程
NSK中国区总代表一行访问中国轴协
Broadpharm提供可切割和不可切割Linker
Hengstler亨士乐AD361217AF.0RBIX电机编码器技术参数
溢流阀HM-011/350 40库存
Rosemount变送器的五大优势特点你知道多少？
天行线缆推动BV电线、RVV护套线产品绿色发展
中药提取-提取浓缩设备-新版GMP导读-附则
T-450粮食重金属检测仪推荐
测量蒸汽流量计投运、维护、停用注意事项
市人民政府关于印发武汉市2019年拥抱蓝天行动方案的通知
材料测试机主机不亮的排除方法
自粘防火包带产品特点 产品图片
液相色谱仪器操作步骤及注意事项
全自动一体化污水提升泵站 实现远程控制无人值守
高压微射流均质机的优势
-25℃低温箱应用行业介绍
this article expands upon the linker information in the adc linker technology in 2021 article. specifically, the cleavable and non-cleavable categories of adc linkers. cleavable linkers use inherent properties of tumor cells for selective release of payloads from the adcs. there are three commonly used mechanisms for cleavable linkers; protease-sensitive peptide linkers, acid sensitive hydrazone linkers, and glutathione-sensitive disulfide linkers.
protease-sensitive cleavable linkers use the dominant proteases found in tumor cell lysosomes for recognition and cleavage of a specific peptide sequence in the linker. a commonly used adc linker makes use of a valine-citrulline (vc) dipeptide, first discovered by dubowchik et al., as an intracellular cleavage mechanism by cathepsin b.
figure 1. adcetris with enzymatically cleavable val-cit linkage.acid-sensitive linkers use a lower ph in the endosomal (ph = 5-6) and lysosomal (ph = 4.8) compartments, in contrast to cytosol (ph = 7.4) to trigger hydrolysis of acid labile groups within a linker such as hydrazone.
glutathione-sensitive linkers use higher concentrations of intracellular glutathione that in the plasma. this causes disulfide bridges to release the payload upon reduction by glutathione.
cleavable linkers may also help with destroying cancer cell adjacent to their targets through a process referred to as bystander effect. the bystander effect occurs when the payload is released near the targeted cancer cell, or a payload diffuses out of one cancer cell and then is absorbed by a second cancer cell.
non-cleavable linkers only degrade when the anti-body degrades. release of the payload occurs mainly in the lysosome after internalization of the adc and degradation of both the antibody and linker. this may be an advantage since it could lead to a lower risk of systemic toxicity. figure 2 shows an example of kadcyla, which uses smcc crosslinker as the non-cleavable linker.
figure 2. kadcyla, shown with the linker in green and the payload in orange, was designed with a non-cleavable linkage.broadpharm offers a wide array of different adc linkers, peg linkers to empower our customer's advanced research worldwide. these compounds feature great aqueous solubility, smart choice of peg length, and a broad selection of functional groups to choose from.
journal reference:1.editorial team, fda grants accelerated approval for sacituzumab govitecan in metastatic triple-negative breast cancer, adc review (2020)
2.fda press release, fda grants accelerated approval to loncastuximab tesirine-lpyl for large b-cell lymphoma, (2021)
3.staudacher, brown, antibody drug conjugates and bystander killing: is antigen-dependent internalisation required?, br j cancer 117, (2017): 1736-1742
订购咨询靶点科技（北京）有限公司
制作牛肉膏蛋白胨培养基配方图文过程（二）
宏伟无人值守称重系统 朝阳10T地磅（开原20吨地磅）明山便携式汽车衡
关于如何选择色谱样品瓶
控温电热板的操作过程
NSK中国区总代表一行访问中国轴协
Broadpharm提供可切割和不可切割Linker
Hengstler亨士乐AD361217AF.0RBIX电机编码器技术参数
溢流阀HM-011/350 40库存
Rosemount变送器的五大优势特点你知道多少？
天行线缆推动BV电线、RVV护套线产品绿色发展
中药提取-提取浓缩设备-新版GMP导读-附则
T-450粮食重金属检测仪推荐
测量蒸汽流量计投运、维护、停用注意事项
市人民政府关于印发武汉市2019年拥抱蓝天行动方案的通知
材料测试机主机不亮的排除方法
自粘防火包带产品特点 产品图片
液相色谱仪器操作步骤及注意事项
全自动一体化污水提升泵站 实现远程控制无人值守
高压微射流均质机的优势
-25℃低温箱应用行业介绍