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

Source: https://onco.cc/terms/hydrophilic-next-gen/  
OnCo record `hydrophilic-next-gen` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Term
- Last checked: 2026-09-09
- Also known as: glucuronide linker; PEGylated linker; beta-glucuronidase-cleavable

## Sources

- Yurkovetskiy et al., A polymer-based antibody-vinca drug conjugate platform (Dolaflexin): characterisation and preclinical efficacy (Cancer Research 2015): https://doi.org/10.1158/0008-5472.CAN-15-0129

## Connected records

- terms: [Drug efflux pumps (ABC transporters)](https://onco.cc/terms/efflux-pump/), [Drug-to-antibody ratio (DAR)](https://onco.cc/terms/dar/), [Linker (ADC)](https://onco.cc/terms/linker/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- drugs: [Izalontamab brengitecan](https://onco.cc/drugs/izalontamab-brengitecan/), [Sacituzumab tirumotecan](https://onco.cc/drugs/sacituzumab-tirumotecan/)
- key papers: [A Polymer-Based Antibody-Vinca Drug Conjugate Platform: Characterization and Preclinical Efficacy](https://onco.cc/key-papers/paper-yurkovetskiy-cancer-res/)

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