PI-1840

SKU: orb1226362

Description

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.

Key Properties

• CAS Number: 1401223-22-0
• MW: 394.4668
• Purity: >98% (HPLC)
• Formula: C₂₂H₂₆N₄O₃
• SMILES: CCCC1=CC=C(C=C1)OCC(=O)N(CC2=NC(=NO2)C3=CN=CC=C3)C(C)C
• Target: Proteasome
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  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 xenografts. Dosage: 150 mg/kg. Administration: Intraperitoneal injection; daily, for 14 days. Result: Inhibited the growth of MDA-MB-231 tumor xenografts by 76%.
• In Vitro:
  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 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 ratio of the expression level of (p-IκBα/control)/(IκBα/control), and decreased the ratio of (p-p65/control)/(p65/control).

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

PI1840

Quick Database Links

Gene Symbol

Proteasome