Noncleavable

Noncleavable is an adjective used to describe a molecule, bond, or linkage that is not susceptible to cleavage under specified conditions. The term is used across disciplines such as chemistry, biochemistry, pharmacology, and materials science. A noncleavable bond resists hydrolysis, reduction, oxidation, or enzymatic cleavage under standard conditions, making it suitable for applications requiring stable linkages or long-term integrity. In practice, what counts as noncleavable depends on the context and conditions; a bond considered noncleavable in one environment may still cleave under more extreme conditions.

In drug delivery and bioconjugation, noncleavable linkers are used to connect a drug to a carrier, such as an antibody. The linker remains intact during circulation and internalization; drug release occurs only after the carrier is degraded inside the target cell, often yielding the active catabolite as a conjugate of the drug with an amino acid or other fragment. This contrasts with cleavable linkers, which release the active drug in response to specific stimuli (pH changes, reducing conditions, or enzymatic action). The choice between noncleavable and cleavable linkers affects pharmacodynamics, stability, and toxicity profiles.

Examples and contexts:

- Noncleavable linkers in antibody-drug conjugates (ADCs) that require cellular degradation to release the payload.

- In materials science, noncleavable linkages provide long-term mechanical stability under expected operating conditions.

See also:

- Cleavable linker

- Antibody-drug conjugate

- Covalent bond

- Linker (chemistry)