Molecular Formula | C22H26N4O3 |
Molar Mass | 394.47 |
Solubility | Soluble in DMSO |
Storage Condition | -20℃ |
Use | PI-1840 is a is a novel rapidly reversible proteasome inhibitor with antitumor activity. It shows selective inhibitor for chymotrypsin-like (CT-L) over trypsin-like and peptidylglutamyl peptide hydrolyzing activities of the proteasome. |
In vitro study | PI-1840 potently inhibits the activity of leucosome MDA-MB-468 in intact human CT-L cancer cells and inhibits proliferation/survival of human MDA-MB-468 cells. In intact cancer cells, PI-1840 inhibits CT-L of activity, induces accumulation of the proteasome substrates p27,Bax, and IKB-α, inhibits survival pathways and viability, and induces apoptosis. |
In vivo study | PI-1840 (150 mg/kg, I. P.) inhibited tumor growth in MDA-MB-231 breast tumor-bearing mice. |
Reference Show more | 1: Kazi A, Ozcan S, Tecleab A, Sun Y, Lawrence HR, Sebti SM. Discovery of PI-1840, a novel noncovalent and rapidly reversible proteasome inhibitor with anti-tumor activity. J Biol Chem. 2014;289(17):11906-11915. doi:10.1074/jbc.M113.533950. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 2.535 ml | 12.675 ml | 25.351 ml |
5 mM | 0.507 ml | 2.535 ml | 5.07 ml |
10 mM | 0.254 ml | 1.268 ml | 2.535 ml |
5 mM | 0.051 ml | 0.254 ml | 0.507 ml |
biological activity | PI-1840 is a reversible and selective chymotrypsin-like (CT-L) inhibitor with IC50 of 27 nM, which has no effect on the proteolytic activities of the other two main proteasomes (trypsin-like (T-L) and postglutamyl-peptide-hydrolysis-like (PGPH-L)). |
in vitro study | PI-1840 effectively inhibits the activity of albase CT-L in intact human MDA-MB-468 cancer cells and inhibits the proliferation/survival of human MDA-MB-468 cells. In intact cancer cells, PI-1840 inhibits CT-L activity, induces accumulation of proteasome substrates p27,Bax, and IκB-α, inhibits survival pathways and viability, and induces apoptosis. |
in vivo study | PI-1840 (150 mg/kg, intraperitoneal injection) inhibits tumor growth in mice with MDA-MB-231 breast tumors. |