| Description | PI-1840（IC50 = 27 nM）is a reversible and selective chymotrypsin-like (CT-L) inhibitor, with little proteasome proteolytic effects on trypsin-like (T-L) and postglutamyl-peptide-hydrolysis-like (PGPH-L). |
| In vitro | PI-1840 potently inhibits proteasomal CT-L activity with IC50 of 0.37 μM in intact human MDA-MB-468 cancer cells, and inhibits proliferation/survival of human MDA-MB-468 cells. [1] 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. [2] |
| In vivo | PI-1840 (150 mg/kg i.p.) 在小鼠中抑制了MDA-MB-231乳腺肿瘤的生长。[2] |
| Cell experiments | Cells are plated in 96-well plates in 100 μL medium and allowed to attach overnight. Cells are then incubated for 120 h with varying concentrations of inhibitors. Media is aspirated and replaced with 100 μL complete media containing 1 mg/ml MTT and incubated for three hours at 37 °C in 5% CO2 humidified incubator. Media is then aspirated and DMSO is added. Cells are incubated for 10 min at room temperature while shaking, and the absorbance is determined at 540 nm using a μQuant spectrophotometric plate reader. The IC50 values are determined using equation under CT-L, T-L, PGPH-L proteolytic activity assays.(Only for Reference) |
| Target activity | Chymotrypsin-like proteasome:27 nM |
| Synonyms | PI 1840 |
| molecular weight | 394.47 |
| Molecular formula | C22H26N4O3 |
| CAS | 1401223-22-0 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | Ethanol: 31 mg/mL (78.6 mM) H2O: < 1 mg/mL (insoluble or slightly soluble) DMSO: 72 mg/mL (182.5 mM) |
| References | 1. Ozcan S, et al. J Med Chem. 2013, 56(10), 3783-3805. 2. Kazi A, J Biol Chem. 2014, 289(17), 11906-11915. |
| Citations | 1. Lü Z, Li X, Li K, et al. Nitazoxanide and related thiazolides induce cell death in cancer cells by targeting the 20S proteasome with novel binding modes. Biochemical Pharmacology. 2022: 114913. |