VR23

Catalog No.S7933

VR23 Chemical Structure

Molecular Weight(MW): 477.88

VR23 is a potent proteasome inhibitor with IC50 of 1 nM, 50-100 nM, and 3 μM for trypsin-like proteasomes, chymotrypsin-like proteasomes, and caspase-like proteasomes, respectively.

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Choose Selective Proteasome Inhibitors

Biological Activity

Description VR23 is a potent proteasome inhibitor with IC50 of 1 nM, 50-100 nM, and 3 μM for trypsin-like proteasomes, chymotrypsin-like proteasomes, and caspase-like proteasomes, respectively.
Targets
Trypsin-like proteasomes [1]
(in Hela cells)
Chymotrypsin-like proteasomes [1]
(in Hela cells)
Caspase-like proteasomes [1]
(in Hela cells)
1 nM 100 nM 3 μM
In vitro

In HeLa cells, VR23 induces ubiquitinated proteins accumulation. In RPMI 8226 and KAS 6 cells, VR23 inhibits cell growth with IC50 of 2.94 and 1.46 μM, respectively. VR23 is also equally effective on both bortezomib (BTZ)-sensitive and -resistant RPMI 8226 and ANBL6 cells cells. When used in combination of bortezomib in the cells above, VR23 shows synergistic effects on cell growth inhibition. In addition, VR23 selectively induces cancer cell apoptosis by causing the accumulation of ubiquitinated cyclin E. [1]

In vivo In ATH490 athymic mice engrafted with MDA-MB-231 metastatic breast cancer cells, VR23 (30mg/kg, i.p.) shows effective antitumor and antiangiogenic activities. VR23 also reduces adverse effects caused by paclitaxel in mice. [1]

Protocol

Kinase Assay:

[1]

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Proteasome assay:

Exponentially growing cells on a 96-well clustered plate are treated with different concentrations of drugs or left untreated (control) for 6 hours. Proteasomes extracted with 0.5% NP40 buffer are mixed with equal amounts of samples in 100 μL total volume, and then incubated with 25 μmol/L of fluorogenic substrates (LRR- specific for trypsin-like activity, LLE-specific for caspase-like activity, and SUVY-specific for chymotrypsin-like activity) in black-bottom 96-well plates at 37°C. Fluorescence is monitored every 5 minutes at the wavelength of 360 nm (excitation) and 480 nm (emission).
Cell Research:

[1]

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  • Cell lines: RPMI 8226, KAS 6, 184B5, and MCF10A cells; bortezomib-resistant RPMI 8226 cells and bortezomib-resistant ANBL6 cells
  • Concentrations: ~20 μM
  • Incubation Time: --
  • Method:

    Clonogenic and SRB assays are carried out. IC50 values are calculated using a sigmoidal dose-response curve (variable slope) using a Graph Pad Prism V 4.02 version.


    (Only for Reference)
Animal Research:

[1]

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  • Animal Models: ATH490 athymic mice engrafted with MDA-MB-231 or RPMI 8226 cancer cells
  • Formulation: 10% DMSO, 12.5% Cremophor, 12.5% ethanol, and 65% saline based diluent
  • Dosages: 30mg/kg
  • Administration: i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 31 mg/mL warmed (64.86 mM)
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 477.88
Formula

C19H16ClN5O6S

CAS No. 1624602-30-7
Storage powder
in solvent
Synonyms N/A

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID