PI-1840

Использование

PI 1840 is a novel rapidly reversible proteasome inhibitor with antitumor activity.

Ферментативный ингибитор

This potent proteasome inhibitor (FW = 394.38 g/mol) selectively targets its chymotrypsin-like activity, or CT-L (IC50 = 27 nM), while showing much weaker action (IC50 values >100 μM) against its Trypsin-Like (T-L) and peptidylglutamyl peptide hydrolyzing, or PGPH activities. Mass spectrometry and equilibrium dialysis show no evidence of covalent linkage of PI-1840 with any proteasomal protein component. In intact cancer cells, PI-1840 inhibits CT-L activity, inducing the accumulation of proteasome substrates p27, Bax and IκB-α, thereby inhibiting survival pathways and viability, and inducing apoptosis. PI=1840 is also >100x more active against the constitutive proteasome, compared to immunoproteasome.