| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
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.
| 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 |
| Molecular Formula |
C22H26N4O3
|
|
|---|---|---|
| Molecular Weight |
394.47
|
|
| Exact Mass |
394.2
|
|
| Elemental Analysis |
C, 66.99; H, 6.64; N, 14.20; O, 12.17
|
|
| CAS # |
1401223-22-0
|
|
| Related CAS # |
|
|
| PubChem CID |
56945245
|
|
| Appearance |
White to off-white solid powder
|
|
| LogP |
3.9
|
|
| Hydrogen Bond Donor Count |
0
|
|
| Hydrogen Bond Acceptor Count |
6
|
|
| Rotatable Bond Count |
9
|
|
| Heavy Atom Count |
29
|
|
| Complexity |
496
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
O=C(N(C(C)C)CC1=NC(C2=CC=CN=C2)=NO1)COC3=CC=C(CCC)C=C3
|
|
| 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 |
|
|
| 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 (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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.
Calculation results
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.
(2) Be sure to add the solvent(s) in order.
|
|---|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
