acetylleucyl-leucyl-norleucinal

Summary

Acetyl-Leu-Leu-Nle-al (ALLN, also known as Calpain Inhibitor I or MG-101) is a synthetic tripeptide aldehyde used extensively as a research tool to inhibit calpains, cathepsins, and the 26S proteasome. It is employed in cell biology to study protein degradation pathways, apoptosis, and NF-κB signaling. It is not approved for therapeutic use in humans.

Mechanism of Action

Reversible inhibitor of cysteine proteases, primarily calpain I and calpain II; also inhibits cathepsins B and L and the proteasome. The aldehyde warhead forms a reversible hemithioacetal with the active-site cysteine of the target protease, blocking substrate cleavage.

Routes of Administration

Goals & Uses

• Proteasome inhibition (research)Ubiquitin Proteasome PathwayHigh
• NF-κB pathway studySignal Transduction ResearchModerate
• Cathepsin inhibition (research)Lysosomal Protease InhibitionModerate
• Apoptosis researchCell Death BiologyModerate
• Calpain inhibition (research)Protease InhibitionHigh

Contraindications

• Human therapeutic useRegulatory/safetyHigh

Adverse Effects

• Off-target protease inhibitionPharmacologicalCommon
• ER stress inductionCell BiologyUncommon
• CytotoxicityCell ViabilityCommon

Drug Interactions

• Other proteasome inhibitors (e.g., MG-132, bortezomib)High
• Cysteine protease substrates/assaysModerate

Population Constraints

• In vivo / human useSafetyAbsolute

Regulatory Status

• European UnionUnapprovedResearch reagent only; no EMA marketing authorization.
• United StatesUnapprovedResearch reagent only; no FDA approval or IND on record.
• United KingdomUnapprovedResearch reagent only; no MHRA authorization.

Not approved by the FDA, EMA, or MHRA for any therapeutic indication. Available exclusively as a research/laboratory reagent. No IND or clinical-phase status on record for this compound.

Evidence & Sources

No sources recorded yet.