Synonym
PI-1840; PI 1840; PI1840
IUPAC/Chemical Name
N-isopropyl-2-(4-propylphenoxy)-N-((3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)methyl)acetamide
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
SMILES Code
O=C(N(C(C)C)CC1=NC(C2=CC=CN=C2)=NO1)COC3=CC=C(CCC)C=C3
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
PI-1840 is a potent and selective chymotrypsin-like (CT-L) inhibitor for with an IC50 value of 27 nM.
In vitro activity:
In the present study, the results revealed that PI‑1840 inhibited the proliferation of OS cells and induced apoptosis, partly due to attenuation of the nuclear factor‑κB (NF‑κB) pathway. In addition, PI‑1840‑induced autophagy was detected, and inhibiting the autophagy of the OS cells led to an increase in the survival rate of the U2‑OS cells rather than of the MG‑63 cells. Furthermore, PI‑1840 attenuated the migration and invasion capabilities of the OS cells.
Reference: Oncol Rep. 2019 May;41(5):2803-2817. https://pubmed.ncbi.nlm.nih.gov/30864717/
In vivo activity:
This study next evaluated the anti-tumor activities of PI-1840 and bortezomib in nude mice bearing solid tumors. The tumor from the mouse treated with vehicle grew from an initial tumor volume of 279 to 910 mm3. Similarly, the tumor from the bortezomib-treated mouse grew from 239 to 852 mm3. In contrast, the tumor from the PI-1840-treated mouse grew from 280 to only 374 mm3 (Fig. 5A). Thus, compared with vehicle, PI-1840 inhibited tumor growth by 85%, whereas bortezomib had little effect on tumor growth. PI-1840 inhibited the growth of MDA-MB-231 tumor xenografts by 76% ((1 − (69/288)) × 100) (p = 0.04), whereas bortezomib inhibited tumor growth by only 8.7% ((1 − (263/288)) × 100), and this was not a statistically significant effect compared with vehicle-treated mice (p = 0.78).
Reference: J Biol Chem. 2014 Apr 25;289(17):11906-11915. https://pubmed.ncbi.nlm.nih.gov/24570003/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
89.0 |
225.62 |
|
| Ethanol |
33.0 |
83.66 |
|
| Water |
0.1 |
0.25 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
394.48
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Chen Y, Chen H, Xie H, Yuan S, Gao C, Yu L, Bi Z. Non‑covalent proteasome inhibitor PI‑1840 induces apoptosis and autophagy in osteosarcoma cells. Oncol Rep. 2019 May;41(5):2803-2817. doi: 10.3892/or.2019.7040. Epub 2019 Mar 1. PMID: 30864717; PMCID: PMC6448088.
2. Ozcan S, Kazi A, Marsilio F, Fang B, Guida WC, Koomen J, Lawrence HR, Sebti SM. Oxadiazole-isopropylamides as potent and noncovalent proteasome inhibitors. J Med Chem. 2013 May 23;56(10):3783-805. doi: 10.1021/jm400221d. Epub 2013 May 13. PMID: 23547706; PMCID: PMC3774303.
3. Kazi A, Ozcan S, Tecleab A, Sun Y, Lawrence HR, Sebti SM. Discovery of PI-1840, a novel noncovalent and rapidly reversible proteasome inhibitor with anti-tumor activity. J Biol Chem. 2014 Apr 25;289(17):11906-11915. doi: 10.1074/jbc.M113.533950. Epub 2014 Feb 25. PMID: 24570003; PMCID: PMC4002098.
In vitro protocol:
1. Chen Y, Chen H, Xie H, Yuan S, Gao C, Yu L, Bi Z. Non‑covalent proteasome inhibitor PI‑1840 induces apoptosis and autophagy in osteosarcoma cells. Oncol Rep. 2019 May;41(5):2803-2817. doi: 10.3892/or.2019.7040. Epub 2019 Mar 1. PMID: 30864717; PMCID: PMC6448088.
2. Ozcan S, Kazi A, Marsilio F, Fang B, Guida WC, Koomen J, Lawrence HR, Sebti SM. Oxadiazole-isopropylamides as potent and noncovalent proteasome inhibitors. J Med Chem. 2013 May 23;56(10):3783-805. doi: 10.1021/jm400221d. Epub 2013 May 13. PMID: 23547706; PMCID: PMC3774303.
In vivo protocol:
1. Kazi A, Ozcan S, Tecleab A, Sun Y, Lawrence HR, Sebti SM. Discovery of PI-1840, a novel noncovalent and rapidly reversible proteasome inhibitor with anti-tumor activity. J Biol Chem. 2014 Apr 25;289(17):11906-11915. doi: 10.1074/jbc.M113.533950. Epub 2014 Feb 25. PMID: 24570003; PMCID: PMC4002098.
1: Kazi A, Ozcan S, Tecleab A, Sun Y, Lawrence HR, Sebti SM. Discovery of PI-1840, a novel noncovalent and rapidly reversible proteasome inhibitor with anti-tumor activity. J Biol Chem. 2014;289(17):11906-11915. doi:10.1074/jbc.M113.533950
Yu J, Xu L, Hong D, Zhang X, Liu J, Li D, Li J, Zhou Y, Liu T. Design, synthesis, and biological evaluation of novel phenol ether derivatives as non-covalent proteasome inhibitors. Eur J Med Chem. 2019 Jan 1;161:543-558. doi: 10.1016/j.ejmech.2018.10.056. Epub 2018 Oct 26. PMID: 30391816.
Chen Y, Chen H, Xie H, Yuan S, Gao C, Yu L, Bi Z. Non‑covalent proteasome inhibitor PI‑1840 induces apoptosis and autophagy in osteosarcoma cells. Oncol Rep. 2019 May;41(5):2803-2817. doi: 10.3892/or.2019.7040. Epub 2019 Mar 1. PMID: 30864717; PMCID: PMC6448088.
Yang Y, Wang K, Wu B, Yang Y, Lai F, Chen X, Xiao Z. Design, synthesis and biological evaluation of triaryl compounds as novel 20S proteasome inhibitors. Bioorg Med Chem Lett. 2020 Nov 1;30(21):127508. doi: 10.1016/j.bmcl.2020.127508. Epub 2020 Aug 24. PMID: 32853683.
