Lactacystin (CAS: 133343-34-7)

Lactacystin is a microbial metabolite isolated from Streptomyces lactacystinaeus and originally identified as an inducer of neurite outgrowth in Neuro2a cells. Subsequent mechanistic studies revealed that lactacystin is converted intracellularly to its active β-lactone form, later termed omuralide, which irreversibly inhibits the 20S proteasome. The inhibitor covalently binds to the catalytic N-terminal threonine residue of specific proteasome β-subunits, establishing the proteasome as a threonine protease. Lactacystin became the first-in-class selective proteasome inhibitor and a foundational chemical biology tool for elucidating the ubiquitin-proteasome pathway. It has been widely used to study cell-cycle regulation, apoptosis, antigen presentation, and neurodegenerative disease models.