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
訂購咨詢靶點科技（北京）有限公司
制作牛肉膏蛋白胨培養(yǎng)基配方圖文過程（二）
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NSK中國區(qū)總代表一行訪問中國軸協(xié)
Broadpharm提供可切割和不可切割Linker
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-25℃低溫箱應用行業(yè)介紹
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
訂購咨詢靶點科技（北京）有限公司
制作牛肉膏蛋白胨培養(yǎng)基配方圖文過程（二）
宏偉無人值守稱重系統(tǒng) 朝陽10T地磅（開原20噸地磅）明山便攜式汽車衡
關(guān)于如何選擇色譜樣品瓶
控溫電熱板的操作過程
NSK中國區(qū)總代表一行訪問中國軸協(xié)
Broadpharm提供可切割和不可切割Linker
Hengstler亨士樂AD361217AF.0RBIX電機編碼器技術(shù)參數(shù)
溢流閥HM-011/350 40庫存
Rosemount變送器的五大優(yōu)勢特點你知道多少？
天行線纜推動BV電線、RVV護套線產(chǎn)品綠色發(fā)展
中藥提取-提取濃縮設備-新版GMP導讀-附則
T-450糧食重金屬檢測儀推薦
測量蒸汽流量計投運、維護、停用注意事項
市人民政府關(guān)于印發(fā)武漢市2019年擁抱藍天行動方案的通知
材料測試機主機不亮的排除方法
自粘防火包帶產(chǎn)品特點 產(chǎn)品圖片
液相色譜儀器操作步驟及注意事項
全自動一體化污水提升泵站 實現(xiàn)遠程控制無人值守
高壓微射流均質(zhì)機的優(yōu)勢
-25℃低溫箱應用行業(yè)介紹