PI 1840

PI-1840 is a potent and selective inhibitor for chymotrypsin-like (CT-L) (IC50 value = 27 ± 0.14 nM) over trypsin-like and peptidylglutamyl peptide hydrolyzing (IC50 values >100 μM) activities of the proteasome. IC50 value: 27 nM(CT-L activities of the proteasome) [1]Target: CT-L inhibitorin vitro: PI-1840 is over 100-fold more selective for the constitutive proteasome over the immunoproteasome. Mass spectrometry and dialysis studies demonstrate that PI-1840 is a noncovalent and rapidly reversible CT-L inhibitor. In intact cancer cells, PI-1840 inhibits CT-L activity, induces the accumulation of proteasome substrates p27, Bax, and IκB-α, inhibits survival pathways and viability, and induces apoptosis. Furthermore, PI-1840 sensitizes human cancer cells to the mdm2/p53 disruptor, nutlin, and to the pan-Bcl-2 antagonist BH3-M6 [1].in vivo: PI-1840 but not bortezomib suppresses the growth in nude mice of human breast tumor xenografts [1].

Signaling Pathways >> Metabolic Enzyme/Protease >> Proteasome

Research Areas >> Cancer

[1]. Kazi A, et al. Discovery of PI-1840, a novel noncovalent and rapidly reversible proteasome inhibitor with anti-tumor activity. J Biol Chem. 2014 Apr 25;289(17):11906-15.

MG-132 | Celastrol | ONX-0914 (PR-957) | Pepstatin | Epoxomicin | Ixazomib (MLN2238) | Calpain Inhibitor I | Oprozomib (ONX 0912) | PD150606 | CEP-18770 (Delanzomib) | RA190 | Capzimin | Gabexate mesylate | VR23 | PD 151746