# Acid-labile hydrazone (AcBut)

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

## TL;DR

The hydrazone linker is acid-sensitive and breaks in the lysosome's low pH. It was used in the calicheamicin ADCs, but is too leaky for most modern designs.

## Summary

The acid-labile hydrazone linker, known as AcBut, breaks in the low pH of the lysosome and was the chemistry used in the calicheamicin ADCs. Hydrazones hydrolyse at pH 4 to 5 but are relatively unstable in plasma, and that leakiness contributed to the off-target toxicity of first-generation ADCs, which is why most modern designs avoid it. Gemtuzumab ozogamicin and inotuzumab ozogamicin use a hydrazone combined with a disulfide. The linker belongs to the Antibody-drug conjugate (ADC) technology and the Linker (ADC) term, is associated with the payload Calicheamicin, and is referenced by the drug record for Gemtuzumab ozogamicin.

## Fields

- Kind: Term
- Last checked: 2026-09-09
- Also known as: acid-cleavable linker

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Hydrazone
- Wikipedia: https://en.wikipedia.org/wiki/Hydrazone

## Connected records

- terms: [Calicheamicin](https://onco.cc/terms/calicheamicin/), [Linker (ADC)](https://onco.cc/terms/linker/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- drugs: [Gemtuzumab ozogamicin](https://onco.cc/drugs/gemtuzumab-ozogamicin/)

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JSON: https://onco.cc/api/v1/entities/hydrazone.json