Product Information
Applications
Biological Information
Primary Targetchymotrypsin-like activity of 20S proteasome
Primary Target IC<sub>50</sub>27 nM for chymotrypsin-like (CT-L) activity of 20S proteasome
Purity≥98% by HPLC
Physicochemical Information
Cell permeableY
Dimensions
Materials Information
Toxicological Information
Safety Information according to GHS
Safety Information
Product Usage Statements
Storage and Shipping Information
Ship Code Ambient Temperature Only
Toxicity Standard Handling
Storage +2°C to +8°C
Protect from Light Protect from light
Do not freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
Packaging Information
Packaged under inert gas Packaged under inert gas
Transport Information
Supplemental Information
Specifications

Documentation

Proteasome Inhibitor XXIII, PI-1840 - Calbiochem SDS

Title

Safety Data Sheet (SDS) 

References

Reference overview
Kazi, A., et al. 2014. J. Biol. Chem. 289, 11906.
Ozcan, S., et al. 2013. J. Med. Chem. 56, 3783.
Data Sheet

Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

Revision15-August-2014 JSW
SynonymsN-Isopropyl-2-(4-propylphenoxy)-N-((3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)methyl)acetamide, PI1840
DescriptionA cell-permeable pyridinyl-oxadiazoloisopropylamide compound that selectively inhibits 20S proteasome β5 CT-L/chymotrypsin-like over β1 C-L/caspase-like (PGPH-L/postglutamyl-peptide hydrolase-like) activity and β2 T-L/trypsin-like activity (IC50 = 18 nM against CT-L and <100 µM against C-L & T-L activity of rabbit 20S proteasome using 20 µM Suc-LLVY-AMC/Cat. No. 539142, Z-LLE-AMC/Cat. No. 539141, and Bz-VGR-AMC as substrate, respectively; 1 h at 37°C) in a noncovalent and reversible manner, being superior to Bortezomib (Cat. No. 504314) in proteasome selectivity over hematopoietic immunoproteasome (120-fold vs. 2-fold selectivity, respectively, in CT-L assays using rabbit proteasome & immunoproteasome). Culture treatment is shown to result in fast cellular CT-L inhibition (>90% of max inhibition within 10 min in MDA-MB-468; 5 µM), resulting in upregulation of proapoptic p27, IκB-α, Bax, as well as Capase-3 & PARP cleavage with concomitant downregulation of Akt & Survivin and phosphorylation of Akt and S6 (20 µM for 48 h in MDA-MB-468 cultures). Shown to exhibits antiproliferation activity in 12 human cancer cultures (IC50 in 5 d from 2.2 µM/MDA-MB-468 to 45.2 µM/RXF 397 by MTT assay), while being less potent against non-cancer HCA2 fibroblast and MCF-10A mammary epithelial cells ((IC50 in 5 d = 86 & 314 µM, respectively), and selectively enhances Nutlin (Cat. No. 444152) sensitivity in p53+/+, but not p53-/-, HCT-116 cultures. Daily intraperitoneal injection (150 mg/kg/d) is reported to result in 76% retardation of MDA-MB-468-derived tumor growth at the end of a 14 d treatment period among mice in vivo with no apparent weight loss, Bortezomib treatment (1 mg/kg, twice weekly i.p.), in comparison, is reported to result in a loss of 6.21% body weight with no significant tumor growth inhibiton.
FormWhite solid
Intert gas (Yes/No) Packaged under inert gas
Chemical formulaC₂₂H₂₆N₄O₃
Structure formulaStructure formula
Purity≥98% by HPLC
SolubilityDMSO (50 mg/ml)
Storage +2°C to +8°C
Protect from light
Do Not Freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
Toxicity Standard Handling
ReferencesKazi, A., et al. 2014. J. Biol. Chem. 289, 11906.
Ozcan, S., et al. 2013. J. Med. Chem. 56, 3783.

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Categories

Life Science Research > Inhibitors and Biochemicals > Small Molecules & Inhibitors > Proteases Inhibitors > Proteasome and Ubiquitination Pathway Inhibitors