{"entity":{"id":"hydrophilic-next-gen","kind":"term","name":"Hydrophilic next-generation linkers (TMALIN, Dolaflexin, sulfonyl-pyrimidine, PEG-containing)","aka":["glucuronide linker","PEGylated linker","beta-glucuronidase-cleavable"],"tldr":"Hydrophilic next-generation linkers have built-in sugars or polyethylene glycol that let ADCs carry more payload without clumping, and they resist efflux pumps.","summary":"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.","asOf":"2026-09-09","links":[{"label":"Yurkovetskiy et al., A polymer-based antibody-vinca drug conjugate platform (Dolaflexin): characterisation and preclinical efficacy (Cancer Research 2015)","url":"https://doi.org/10.1158/0008-5472.CAN-15-0129"}],"tags":[],"related":["efflux-pump","dar"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["sacituzumab-tirumotecan","izalontamab-brengitecan"],"companies":[],"institutions":[],"pathways":[],"terms":["linker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-yurkovetskiy-cancer-res"],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry","wikipediaChecked":"2026-09-22"},"route":"/terms/hydrophilic-next-gen/","neighbours":{"term":[{"id":"efflux-pump","kind":"term","name":"Drug efflux pumps (ABC transporters)","route":"/terms/efflux-pump/"},{"id":"dar","kind":"term","name":"Drug-to-antibody ratio (DAR)","route":"/terms/dar/"},{"id":"linker","kind":"term","name":"Linker (ADC)","route":"/terms/linker/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"drug":[{"id":"izalontamab-brengitecan","kind":"drug","name":"Izalontamab brengitecan","route":"/drugs/izalontamab-brengitecan/"},{"id":"sacituzumab-tirumotecan","kind":"drug","name":"Sacituzumab tirumotecan","route":"/drugs/sacituzumab-tirumotecan/"}],"paper":[{"id":"paper-yurkovetskiy-cancer-res","kind":"paper","name":"A Polymer-Based Antibody-Vinca Drug Conjugate Platform: Characterization and Preclinical Efficacy","route":"/key-papers/paper-yurkovetskiy-cancer-res/"}]}}