PI-1840

Research use only, not for human use.

PI-1840 is a potent, selective, noncovalent, reversible inhibitor for proteasome chymotrypsin-like (CT-L) activity with IC50 of 27 nM.

PI-1840 is a potent, selective, noncovalent, reversible inhibitor for proteasome chymotrypsin-like (CT-L) activity with IC50 of 27 nM, shows no effect on trypsin-like and peptidylglutamyl peptide hydrolyzing activities (IC50>100 uM); also displays 100-fold more selectivity for the constitutive proteasome over the immunoproteasome; induces the accumulation of proteasome substrates p27, Bax, and IκB-α, inhibits survival pathways and viability, and induces apoptosis in intact cancer cells, also sensitizes human cancer cells to the mdm2/p53 disruptor Nutlin; suppresses the growth in nude mice of human breast tumor xenografts.

PI-1840 (5-60 μM; 24 and 48 h) inhibits the proliferation of MG-63 and U2-OS cells.PI-1840 (40 μM (U2-OS cells) and 60 μM (MG-63 cells); 24 and 48 h) induces cell cycle arrest at the G2/M phase.PI-1840 (15-60 μM (MG-63 cells), 10-40 μM (U2-OS cells); 48 h) induces apoptosis through NF-κB pathway in MG-63 and U2-OS cells. PI-1840 induces autophagy in MG-63 and U2-OS cells. Cell Viability Assay Cell Line:MG-63 and U2-OS cells Concentration:5, 10, 20, 40, 80, and 160 μM Incubation Time:24 and 48 hours Result:Inhibited cell growth in a dose-dependent manner with IC50 values of 108.40 μM (MG-63, 24 h), 59.58 μM (MG-63, 48 h), 86.43 μM (U2-OS, 24 h), and 38.83 μM (U2-OS, 48 h), respectively.Apoptosis Analysis Cell Line:MG-63 and U2-OS cells Concentration:15, 30, and 60 μM (MG-63 cells), 10, 20, and 40 μM (U2-OS cells)Incubation Time:48 hours Result:Increased the apoptotic rates of the two cell lines in a dose-dependent manner.Cell Cycle Analysis Cell Line:MG-63 and U2-OS cells Concentration:40 μM (U2-OS cells) and 60 μM (MG-63 cells)Incubation Time:24 and 48 hours Result:Increased in the G2/M phase cell population.Western Blot Analysis Cell Line:MG-63 and U2-OS cells Concentration:40 μM (U2-OS cells) and 60 μM (MG-63 cells)Incubation Time:24 and 48 hours Result:Increased the cell cycle regulation-associated proteins about p21, p27 and WEE1.Western Blot AnalysisCell Line:MG-63 and U2-OS cells Concentration:15, 30, and 60 μM (MG-63 cells), 10, 20, and 40 μM (U2-OS cells)Incubation Time:48 hours Result:Increased the ratio of the expression level of (p-IκBα/control)/(IκBα/control), and decreased the ratio of (p-p65/control)/(p65/control).

PI-1840 (150 mg/kg; i.p.; daily, for 14 d) inhibits the growth of human breast tumor xenografts in nude mice. Animal Model:Female nude mice with MDA-MB-231 xenograftsDosage:150 mg/kg Administration:Intraperitoneal injection; daily, for 14 days Result:Inhibited the growth of MDA-MB-231 tumor xenografts by 76%.

PI1840

Proteasome/Ubiquitin

Proteasome

Chymotrypsin-likeproteasome

Cancer

——

1401223-22-0

394.4668

C22H26N4O3

>98% (HPLC)

10 mM in DMSO

CCCC1=CC=C(C=C1)OCC(=O)N(CC2=NC(=NO2)C3=CN=CC=C3)C(C)C

Acetamide, N-(1-methylethyl)-2-(4-propylphenoxy)-N-[[3-(3-pyridinyl)-1,2,4-oxadiazol-5-yl]methyl]-

(-20℃)

With Ice Pack

≥ 2 years