In the world of antibody-drug conjugates (ADCs), self-immolative linkers are a clever chemical innovation: once activated, they undergo a built-in cascade that cleanly decomposes to release the payload in its active form.

The best-known system is undoubtedly p-aminobenzyl carbamate (PABC)—used in multiple FDA-approved ADCs like Adcetris® and Polivy®. But the field is much richer than that. Here at SigutLabs, we’ve explored a wide variety of self-immolative designs in the lab, from classical to cutting-edge.

Highlights from Our Lab Bench

✔ PABC (p-aminobenzyl carbamate)
The gold standard for 1,6-elimination-based release. Reliable, well-understood, and widely adopted.

✔ Other 1,6-Elimination Systems
For instance, glucuronidase-cleavable linkers follow a similar path and offer enzyme-targeted payload release.

✔ Cyclization-Driven Mechanisms
Here, the driving force is the formation of a 5- or 6-membered ring. We’ve tested systems like carbamate–hydrazone hybrids and 1,4-aminobutyl scaffolds.

✔ Ethylenediamine-Based Linkers
A powerful cyclization-based approach: through amidine formation or imine hydrolysis, it delivers great performance. Pro tip: alkylating the amine speeds up the immolation!

✔ Phosphate-Triggered Systems
An emerging idea with exciting potential, though not yet used in ADCs. We’d like to highlight the work of Ondřej Baszczynski, one of the early pioneers in this space.

✔ 1,4-Elimination Pathways
Frequently found in disulfide-based linkers, which offer redox-triggered drug release.

What Makes a Good Self-Immolative Linker?

It all comes down to control: a clean, predictable breakdown with no toxic side-products and full release of the active drug.

Custom Linkers for Better ADCs

At SigutLabs, we specialize in custom linker-payload synthesis, including non-standard and exploratory self-immolative designs. If you’re building next-gen ADCs and need support with your linker chemistry—especially outside the usual toolbox—we’re here to help.

Contact us to discuss your project!