PI-1840

Alias: PI1840; PI 1840; PI-1840
Cat No.:V0694 Purity: ≥98%
PI-1840 (PI1840; PI 1840) is a reversible/non-covalent and selective inhibitor of chymotrypsin-like (CT-L) activity of proteasome with potential anticancer activity.
PI-1840 Chemical Structure CAS No.: 1401223-22-0
Product category: Proteasome
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

PI-1840 (PI1840; PI 1840) is a selective, reversible, non-covalent inhibitor of the proteasome's chymotrypsin-like (CT-L) activity that may have anticancer properties. With an IC50 of 27 nM, it suppresses the proteasome's chymotrypsin-like activity. When human breast tumor xenografts were given to naked mice, PI-1840 demonstrated remarkable antitumor activity.

Biological Activity I Assay Protocols (From Reference)
Targets
Chymotrypsin-like proteasome (IC50 = 27 nM)
ln Vitro
PI-1840 potently suppresses the proliferation and survival of human MDA-MB-468 cells, as well as the proteasomal CT-L activity, with an IC50 of 0.37 μM in intact cancer cells.[1] PI-1840 suppresses CT-L activity in intact cancer cells, causes apoptosis, blocks survival pathways and viability, and causes the proteasome substrates p27, Bax, and IκB-α to accumulate.[2]
ln Vivo
PI-1840 (150 mg/kg i.p.) inhibits the growth of MDA-MB-231 breast tumors in mice.[2]
Enzyme Assay
In the high-throughput screen, the 50,000 compound library from ChemBridge is assayed (at 10 μM) for inhibitory activity against the CT-L proteolytic activity of the purified rabbit 20S proteasome using fluorogenic peptides as substrates. Using the matching fluorogenic peptides, selectivity for CT-L over T-L and PGPH-L is tested. In summary, 20 μM Suc-Leu-Leu-Val-Tyr-AMC for the CT-L activity, Bz-Val-Gly-Arg-AMC for the T-L activity, and benzyloxycarbonyl Z-Leu-Leu-Glu-AMC for the PGPH-L activity are incubated with 1 nM of purified 20S rabbit proteasome for 1 hour at 37 °C in 100 μL of assay buffer (50 mM Tris-HCl, pH 7.6) with or without compound. After incubation, a WALLAC Victor2 1420 Multilabel Counter equipped with an excitation filter of 355 nm and an emission filter of 460 nm is used to measure the production of hydrolyzed 7-amido-4-methyl-coumarin (AMC) groups. The released amount of AMC falls inside the linear range. As a positive control for IC50 calculations, bonetezomib is utilized. In order to assess proteasome activity in whole cells, the same assay described above is performed using extracts (5 μg) from cultured cell lysate rather than 20S rabbit proteasome.
Cell Assay
In 96-well plates, cells are plated in 100 μL medium and left to adhere for the entire night. Next, different inhibitor concentrations are added to the cells and incubated for 120 hours. Aspirate the media, replace it with 100 μL of complete media containing 1 mg/ml of MTT, and incubate for three hours at 37 °C in an incubator with 5% CO2 humidification. After aspirating the media, DMSO is added. A μQuant spectrophotometric plate reader is used to measure the absorbance at 540 nm after the cells are shaken and incubated for 10 minutes at room temperature. Under the CT-L, T-L, and PGPH-L proteolytic activity tests, the IC50 values are calculated using the equation.
Animal Protocol
Nude mice bearing human breast cancer MDA-MB-231 xenografts
~150 mg/kg daily
i.p.
References

[1]. J Med Chem . 2013 May 23;56(10):3783-805.

[2]. J Biol Chem . 2014 Apr 25;289(17):11906-11915.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C22H26N4O3
Molecular Weight
394.47
Exact Mass
394.20
Elemental Analysis
C, 66.99; H, 6.64; N, 14.20; O, 12.17
CAS #
1401223-22-0
Appearance
Solid powder
SMILES
CCCC1=CC=C(C=C1)OCC(=O)N(CC2=NC(=NO2)C3=CN=CC=C3)C(C)C
InChi Key
ZVVXAODXPVWGMF-UHFFFAOYSA-N
InChi Code
InChI=1S/C22H26N4O3/c1-4-6-17-8-10-19(11-9-17)28-15-21(27)26(16(2)3)14-20-24-22(25-29-20)18-7-5-12-23-13-18/h5,7-13,16H,4,6,14-15H2,1-3H3
Chemical Name
N-propan-2-yl-2-(4-propylphenoxy)-N-[(3-pyridin-3-yl-1,2,4-oxadiazol-5-yl)methyl]acetamide
Synonyms
PI1840; PI 1840; PI-1840
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~78 mg/mL (~197.7 mM)
Water: <1 mg/mL
Ethanol: ~33 mg/mL (~83.7 mM)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.5350 mL 12.6752 mL 25.3505 mL
5 mM 0.5070 mL 2.5350 mL 5.0701 mL
10 mM 0.2535 mL 1.2675 mL 2.5350 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
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Biological Data
  • PI-1840

    PI-1833 and its potent analog PI-1840 are selective inhibitors for CT-L activity in vitro. J Biol Chem. 2014 Apr 25;289(17):11906-15.
  • PI-1840

    Antitumor efficacy of PI-1840 and bortezomib against human breast cancer MDA-MB-231 xenografts in nude mice. J Biol Chem. 2014 Apr 25;289(17):11906-15.
  • PI-1840

    Selective inhibition of the proteasomal CT-L activity in whole cells, accumulation of proteasome substrate proteins, inhibition of cell survival pathways, and induction of apoptosis. J Biol Chem. 2014 Apr 25;289(17):11906-15.
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