Salinosporamide A

Potent, irreversible inhibitor of all the 3 proteolytic activities of the mammalian 20S proteasome. beta5 subunit: chymotrypsin-like (EC50 = 3.5nM) beta2 subunit: trypsin-like (EC50 = 28nM) beta1 subunit: caspase-like or peptidyl-glutamyl peptide-hydrolyzing (PGPH) (EC50 = 430nM) Potent anticancer compound. Triggers apoptosis, with distinct proteasome activity and mechanism of action compared to bortezomib (Velcade) (Prod. No. AG-CR1-3602). Most potent suppressor of NF-kappaB activation, compared with bortezomib, MG-132 (Prod. No. AG-CP3-0011), N-acetyl-leucyl-leucyl-norleucinal (ALLN) and lactacystin (Prod. No. AG-CN2-0104). Inhibitor of TNF-alpha, IL-1, IL-6, ICAM-1 and VEGF synthesis. Displays a longer inhibition duration than bortezomib. Potent antileukemic activity against bortezomib-resistant leukemia cells.