Lactacystin (CAS: 133343-34-7)

C₁₅H₂₄N₂O₇S

• Induces neuritogenesis [1, 3].
• Potent and selective irreversible proteasome inhibitor. Specifically inhibits 20S proteasome (MCP; multicatalytic complex) [2, 4, 7]. Blocks proteasome activity by targeting the catalytic β-subunit [5].
• Apoptosis inducer [4, 6, 7, 10].
• Anticancer compound [6, 10, 13].
• Upregulates HSP70 and HSP22 [8].
• Induces differentiation and inhibits cell cycle progression in several tumor cell lines [9].
• Inhibits NF-κB activation by inhibiting IκB degradation [11].
• Cathepsin A inhibitor [12].
• β-Secretase activity inhibitor [14].
• Anti-adipogenic [15, 16].
• Autophagy inducer [17].

1. Lactacystin, a novel microbial metabolite, induces neuritogenesis of neuroblastoma cells: S. Omura, et al.; J. Antibiot. (Tokyo) 44, 113 (1991)
2. Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin: G. Fenteany, et al.; Science 268, 726 (1995)
3. Structure-activity relationships of lactacystin, the first non-protein neurotrophic factor: T. Nagamitsu, et al.; J. Antibiot. (Tokyo) 48, 747 (1995)
4. Lactacystin, a specific inhibitor of the proteasome, induces apoptosis in human monoblast U937 cells: S. Imajoh-Ohmi, et al.; BBRC 217, 1070 (1995)
5. Lactacystin and clasto-lactacystin beta-lactone modify multiple proteasome beta-subunits and inhibit intracellular protein degradation and major histocompatibility complex class I antigen presentation: A. Craiu, et al.; J. Biol. Chem. 272, 56 (1997)
6. The proteasome inhibitor lactacystin induces apoptosis and sensitizes chemo- and radioresistant human chronic lymphocytic leukaemia lymphocytes to TNF-alpha-initiated apoptosis: J. Delic, et al.; Br. J. Cancer 77, 1103 (1998)
7. Lactacystin, proteasome function, and cell fate: G. Fenteany & S.L. Schreiber; J. Biol. Chem. 273, 8545 (1998) (Review)
8. Proteasome inhibitors MG132 and lactacystin hyperphosphorylate HSF1 and induce hsp70 and hsp27 expression: D. Kim, et al.; BBRC 254, 264 (1999)
9. Induction of G1 arrest and selective growth inhibition by lactacystin in human umbilical vein endothelial cells: S.I. Kumeda, et al.; Anticancer Res. 19, 3961 (1999)
10. Lactacystin activates FLICE (caspase 8) protease and induces apoptosis in Fas-resistant adult T-cell leukemia cell lines: Y. Yamada, et al.; Eur. J. Haematol. 64, 315 (2000)
11. Inhibitory and stimulatory effects of lactacystin on expression of nitric oxide synthase type 2 in brain glial cells. The role of Ikappa B-beta: M. Stasiolek, et al.; J. Biol. Chem. 275, 24847 (2000)
12. Lactacystin inhibits cathepsin A activity in melanoma cell lines: L. Kozlowski, et al.; Tumour Biol. 22, 211 (2001)
13. Lactacystin exhibits potent anti-tumor activity in an animal model of malignant glioma when administered via controlled-release polymers: F.G. Legnani, et al.; J. Neurooncol. 77, 225 (2006)
14. Lactacystin decreases amyloid-beta peptide production by inhibiting beta-secretase activity: P. Kienlen-Campard, et al.; J. Neurosci. Res. 84, 1311 (2006)
15. Lactacystin inhibits 3T3-L1 adipocyte differentiation through induction of CHOP-10 expression: X. Li, et al.; BBRC 350, 1 (2006)
16. Inhibition of human preadipocyte proteasomal activity by HIV protease inhibitors or specific inhibitor lactacystin leads to a defect in adipogenesis, which involves matrix metalloproteinase-9: S. De Barros, et al.; J. Pharmacol. Exp. Ther. 320, 291 (2007)
17. Mechanisms of cross-talk between the ubiquitin-proteasome and autophagy-lysosome systems: V.I. Korolchuk, et al.; FEBS Lett. 584, 1393 (2010)