《Sulfatase-cleavable linkers for antibody-drug conjugates》 was published in Chemical Science in 2020. These research results belong to Bargh, Jonathan D.; Walsh, Stephen J.; Isidro-Llobet, Albert; Omarjee, Soleilmane; Carroll, Jason S.; Spring, David R.. Reference of 2,4,6-Trichloropyrimidine The article mentions the following:
Antibody-drug conjugates (ADCs) are a class of targeted drug delivery agents combining the cell-selectivity of monoclonal antibodies (mAbs) and the cytotoxicity of small mols. These two components are joined by a covalent linker, whose nature is critical to the efficacy and safety of the ADC. Enzyme-cleavable dipeptidic linkers have emerged as a particularly effective ADC linker type due to their ability to selectively release the payload in the lysosomes of target cells. However, these linkers have a number of drawbacks, including instability in rodent plasma and their inherently high hydrophobicity. Here we show that arylsulfate-containing ADC linkers are cleaved by lysosomal sulfatase enzymes to tracelessly release their payload, while circumventing the instability problems associated with dipeptide-linkers. When incorporated with trastuzumab and the highly potent monomethyl auristatin E (MMAE) payload, the arylsulfate-containing ADC 2 and ADC 3 were more cytotoxic than the non-cleavable ADC 4 against HER2-pos. cells, while maintaining selectivity over HER2-neg. cells. We propose that the stability, solubility and synthetic tractability of our arylsulfate linkers make them an attractive new motif for cleavable ADC linkers, with clear benefits over the widely used dipeptidic linkers. After reading the article, we found that the author used 2,4,6-Trichloropyrimidine(cas: 3764-01-0Reference of 2,4,6-Trichloropyrimidine)
2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Reference of 2,4,6-Trichloropyrimidine
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia