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Carfilzomib (PR-171)

Catalog No.
A1933
Proteasome inhibitor,epoxomicin analog
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$150.00
In stock
Evaluation Sample
$28.00
In stock
5mg
$105.00
In stock
10mg
$133.00
In stock
25mg
$220.00
In stock

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Email: [email protected]

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Background

An epoxomicin derivate with potential antineoplastic activity. It irreversibly binds to and inhibits the chymotrypsin-like activity of the 20S proteasome, an enzyme responsible for degrading a large variety of cellular proteins. Inhibition of proteasome-mediated proteolysis results in an accumulation of polyubiquinated proteins, which may lead to cell cycle arrest, induction of apoptosis, and inhibition of tumor growth.

References:
1. Guido Cavaletti, et al., Leukemia & Lymphoma (2010), 51(7), 1178-1187.
2. Girija Dasmahapatra, et al., Blood (2010), 115(22), 4478-4487.

Product Citation

Chemical Properties

Physical AppearanceA solid
StorageDesiccate at -20°C
M.Wt719.91
Cas No.868540-17-4
FormulaC40H57N5O7
SynonymsPR 171,PR171,PR-171,Carfilzomib
Solubility≥36.0mg/mL in DMSO
Chemical Name(2S)-4-methyl-N-[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]-4-phenylbutanoyl]amino]pentanamide
SDFDownload SDF
Canonical SMILESCC(C)CC(C(=O)C1(CO1)C)NC(=O)C(CC2=CC=CC=C2)NC(=O)C(CC(C)C)NC(=O)C(CCC3=CC=CC=C3)NC(=O)CN4CCOCC4
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Protocol

Cell experiment [1]:

Cell lines

HT-29 colorectal adenocarcinoma cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reaction Conditions

1 h; IC50=9 nM

Applications

Incubation of HT-29 colorectal adenocarcinoma cells with PR-171 for 1 h resulted in a dose-dependent inhibition of all three proteasome catalytic activities with the chymotrypsin-like activity exhibiting the greatest sensitivity (IC50=9 nM). The caspase-like and trypsin-like activities were inhibited to a greater extent in the cellular assay (IC50=150–200 nM) than in the isolated enzyme assay (IC50>1 μM).

Animal experiment [1]:

Animal models

BNX mice

Dosage form

5 mg/kg delivered weekly; QDx2; intravenous injection

Applications

The antitumor activity of PR-171 was evaluated in BNX mice bearing established human tumor xenografts derived from three tumor cell lines: HT-29 (colorectal adenocarcinoma), RL (B cell lymphoma ), and HS-Sultan (Burkitt’s lymphoma). All PR-171 dosing schedules (up to 5 mg/kg delivered weekly QDx2) were tolerated in the tumor-bearing animals, resulting in weight loss of <10%. The results show that the activity of PR-171 is dose and schedule dependen. And PR-171 also suppressed proteasome activity in blood and adrenals.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Demo S D, Kirk C J, Aujay M A, et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome[J]. Cancer research, 2007, 67(13): 6383-6391.

Biological Activity

Description Carfilzomib (PR-171) is an irreversible inhibitor of proteasome with IC50 of <5 nM.
Targets Proteasome          
IC50 5 nM          

Quality Control

Chemical structure

Carfilzomib (PR-171)

Related Biological Data

Carfilzomib
Synchronous trophozoites were treated with 100 nM or 1μ M carfilzomib for the indicated times followed by inhibitor wash out. Parasites were placed in fresh media, and proteasome activities of all samples were determined by MV151 labeling at 10 hr after inhibitor washout. Quantification of the putative β5 subunit labeling is shown in the graph below the gel image.

Related Biological Data

Carfilzomib (PR-171)

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Carfilzomib (PR-171)

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Carfilzomib (PR-171)

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Carfilzomib (PR-171)

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Carfilzomib (PR-171)

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Carfilzomib (PR-171)