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Carfilzomib (PR-171)Proteasome inhibitor,epoxomicin analog

Carfilzomib (PR-171)

Catalog No. A1933
Size Price Stock Qty
Evaluation Sample $28.00 In stock
5mg $50.00 In stock
10mg $70.00 In stock
50mg $140.00 In stock
100mg $190.00 In stock

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Sample solution is provided at 25 µL, 10mM.

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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)

Related Biological Data

Carfilzomib (PR-171)

Biological Activity

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

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.

Reacting condition

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

Application

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.

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Chemical Properties

Cas No. 868540-17-4 SDF Download SDF
Synonyms PR 171,PR171,PR-171,Carfilzomib
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
Canonical SMILES CC(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
Formula C40H57N5O7 M.Wt 719.91
Solubility Soluble in DMSO > 10 mM Storage Desiccate at -20°C
General tips For 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.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

Research Update

1. Carfilzomib: a novel agent for multiple myeloma. J Pharm Pharmacol. 2013 Aug;65(8):1095-106. doi: 10.1111/jphp.12072. Epub 2013 Apr 24.
Abstract
Carfilzomib has been review as a new agent to treat relapsed and refractory MM.
2. A novel Bruton's tyrosine kinase inhibitor CC-292 in combination with the proteasome inhibitor carfilzomib impacts the bone microenvironment in a multiple myeloma model with resultant anti-myeloma activity. Leukemia. 2014 Feb 12. doi: 10.1038/leu.2014.69. [Epub ahead of print]
Abstract
Instead of inhibiting the formation of OC sealing zone alone, the combination of cartfilzomib and CC-292 exhibited synergistic anti-MM activities, including inhibition of both sealing zone formation and differentiation of OC, suppression of tumor burden in a mouse model and increasing bone volume.
3. In vitro and in vivo therapeutic efficacy of carfilzomib in mantle cell lymphoma: targeting the immunoproteasome. Mol Cancer Ther. 2013 Nov;12(11):2494-504. doi: 10.1158/1535-7163.MCT-13-0156. Epub 2013 Aug 29.
Abstract
Carfilzomib, a proteasome inhibitor, is an anti-MCL agent that concentration-dependently inhibited cell growth, induced apoptosis and suppressed survival signaling pathways NF-KB and STAT3 without causing toxicity to normal peripheral blood mononuclear cells. Immunoproteasome, particularly LMP2, plays an indispensible role in anti-MCL activity of carfilzomib.
4. Carfilzomib-Associated Tumor Lysis Syndrome. Pharmacotherapy. 2014 Jan 4. doi: 10.1002/phar.1397. [Epub ahead of print]
Abstract
Even though it is an FDA-approved anti-MM drug with less than 1% TLS frequency, carfilzomib has been associated with TLS development in a 55-year-old male patient with relapsed MM.
5. Carfilzomib: a second-generation proteasome inhibitor for the treatment of relapsed and refractory multiple myeloma. Ann Pharmacother. 2013 Jan;47(1):56-62. doi: 10.1345/aph.1R561. Epub 2013 Jan 8.
Abstract
Carfilzomib, an FDA-approved anti-MM drug, has been evaluated in the treatment of patients who have relapsed and refractory MM and received prior bortezomib and thalidomide or lenalidomide.

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.