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termsTerm

Hydrophilic next-generation linkers (TMALIN, Dolaflexin, sulfonyl-pyrimidine, PEG-containing)

aka glucuronide linker, PEGylated linker, beta-glucuronidase-cleavable

Hydrophilic next-generation linkers have built-in sugars or polyethylene glycol that let ADCs carry more payload without clumping, and they resist efflux pumps.

Glucuronide-triggered linkers (cleaved by beta-glucuronidase), PEGylated linkers and sulfatase- or phosphatase-triggered designs increase hydrophilicity so drug-to-antibody ratios of eight are stable, reduce liver clearance and can yield released species that are poorer efflux-pump substrates. Several appear in next-generation topoisomerase-I and tubulin ADCs from Chinese and US developers.

Category
ADC chemistry

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