Carfilzomib (PR-171)

Catalog No.S2853

Carfilzomib (PR-171) Chemical Structure

Molecular Weight(MW): 719.91

Carfilzomib (PR-171) is an irreversible proteasome inhibitor with IC50 of <5 nM in ANBL-6 cells, displayed preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, but little or no effect on the PGPH and T-L activities.

Size Price Stock Quantity  
In DMSO USD 476 In stock
USD 170 In stock
USD 270 In stock
USD 670 In stock
USD 870 In stock

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3 Customer Reviews

  • Validation of activity and specificity of chemical inhibitors of; ATM, ATR, and DNAPK. H460 cells were treated with 1 uM camptothecin (CPT) or 20 ug/ml bleomycin for 1 h in the presence of the indicated inhibitors: DNAPK-i1—NU7026, DNAPK-i2—NU7441. MSH6,

    Sci Transl Med 2014 6(250), 250ra112. Carfilzomib (PR-171) purchased from Selleck.

    MM.1S cells were treated with or without carfilzomib (10 nM) in the presence or absence of TAS-117 (0.5 uM) for 24 h. Whole cell lysates were subjected to western blotting using CHOP, PARP, and GAPDH Abs.The graph represents fold changes of CHOP density relative to GAPDH.

    Cancer Res 2014 74(16), 4458-69. Carfilzomib (PR-171) purchased from Selleck.

  • Transduction at 24 h is indicated as normalized luciferase activity. HeLa cells were cotreated with 1 uM Carfilzomib and 500 vg/cell rAAV2-EGFP, and transduction was analyzed by flow cytometry at 24 h. Bright-field and EGPF fluorescence images at 24 h postransduction of cells visually indicating transduction.

    J Virol 2013 87(23), 13035-41. Carfilzomib (PR-171) purchased from Selleck.

Purity & Quality Control

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Notes:

2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

Biological Activity

Description Carfilzomib (PR-171) is an irreversible proteasome inhibitor with IC50 of <5 nM in ANBL-6 cells, displayed preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, but little or no effect on the PGPH and T-L activities.
Targets
Proteasome [1]
(ANBL-6 cells)
5 nM
In vitro

Carfilzomib inhibits proliferation in a variety of cell lines and patient-derived neoplastic cells, including multiple myeloma, and induced intrinsic and extrinsic apoptotic signaling pathways and activation of c-Jun-N-terminal kinase (JNK). Carfilzomib reveals enhanced anti-MM activity compared with bortezomib, overcome resistance to bortezomib and other agents, and acts synergistically with dexamethasone (Dex). Carfilzomib shoes preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, with over 80% inhibition at doses of 10 nM. Short exposure to low-dose Carfilzomib leads to preferential binding specificity for the β5 constitutive 20S proteasome and the β5i immunoproteasome subunits. Measurement of caspase activity in ANBL-6 cells pulsed with Carfilzomib reveals substantial increases in caspase-8, caspase-9, and caspase-3 activity after 8 hours, giving a 3.2-, 3.9- and 6.9-fold increase, respectively, over control cells after 8 hours. In carfilzomib pulse-treated cells, the mitochondrial membrane integrity is decreased to 41% (Q1 + Q2), compared with 75% in vehicle-treated control cells. [1] In another study, Carfilzomib has also shown preclinical effectiveness against hematological and solid malignancies. [2] Carfilzomib directly inhibits osteoclasts formation and bone resorption. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MM.1S M1LIVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1XPe|AuOTByIH7N NUPoNVM1PDhiaB?= M2ryZmlEPTEEoE5CpFExKG6P M4\qSlI2OzF{NUSz
NCI-H929  NIDrdnRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml74NE0yODBibl2= M4XoO|Q5KGh? MYTJR|UxKD4EoEG0JI5O NVLLS4pWOjV|MUK1OFM>
SUDHL16  NHn1fFhCeG:ydH;zbZMhSXO|c3H5 NY\PcIVZOi534pETN{42KG6P M1\WVFQ5KGh? NGn0U2hmdmijbnPld{B1cGViY3XscEBl\WG2aDDjc{11emWjdH3lcpQhf2m2aDDBR3kyOjF3 M13XbVI2OjN7OUO1
SUDHL14 NXPseI9USXCxcITvd4l{KEG|c4PhfS=> NWHGXII{Oi534pETN{42KG6P NIXr[2s1QCCq MmPn[Y5p[W6lZYOgeIhmKGOnbHyg[IVifGhiY3:teJJm[XSvZX70JJdqfGhiQVPZNVIyPQ>? M1fV[VI2OjN7OUO1
U2932 NVjmTHh2SXCxcITvd4l{KEG|c4PhfS=> NGO4c5IzNjYkgKOzMlUhdk1? MU[0PEBp NVX5[WFY\W6qYX7j[ZMhfGinIHPlcIwh\GWjdHigZ48ufHKnYYTt[Y51KHerdHigRWN[OTJzNR?= NF;hcZozPTJ|OUmzOS=>
P-UMSCC-1 M2jIfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{\KR2lEPTB;MUGuNkBvVQ>? MmnmNlQ6OTVyM{m=
R-UMSCC-1 MoTtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkT1TWM2OD1{Mkm0JI5O NGDjfWUzPDlzNUCzPS=>
P-Cal33 MmPDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVXJR|UxRTF5LkOgcm0> NYDCO5dTOjR7MUWwN|k>
R-Cal33 NUTsOXZtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHX1fplKSzVyPUGxNVIhdk1? NVLaSlhwOjR7MUWwN|k>
Jurkat NXzmVIkxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{fhclEuOTGwTR?= Ml:1OFghcA>? Mn\DbY5pcWKrdIOgeIhmKGOnbHygdJJwdGmoZYLheIlwdiClbz30doVifG2nboSge4l1cCC4b4Lpco9{fGG2 Ml\ONlQ5ODFzMki=
Jurkat NF7ZZlhCeG:ydH;zbZMhSXO|c3H5 NWjifFkyQCCwTR?= M4DGNFI1NzR6IHi= NH;zc4lqdmS3Y3XzJIFxd3C2b4Ppd{wh[2G|cHHz[UBi[3SrdnH0bY9vNCCjbnSgVGFTWCClbHXheoFo\SClbz30doVifG2nboSge4l1cCC4b4Lpco9{fGG2 NWfmNWZYOjR6MEGxNlg>
UMSCC-22A NYC2Z2IySXCxcITvd4l{KEG|c4PhfS=> NI\nOHQzODBibl2= NEG2eo8zPCCq NVjlU|B5cW6mdXPlJJRp\SClZXzsJIFxd3C2b4Ppd{Bkdy22cnXheI1mdnRid3n0bEBQVlhiMEmxNi=> NIO3XnMzOjl{OUiwNy=>
UMSCC-22B NIn2S|lCeG:ydH;zbZMhSXO|c3H5 MnXnNlAxKG6P MnzMNlQhcA>? NVnafJpncW6mdXPlJJRp\SClZXzsJIFxd3C2b4Ppd{Bkdy22cnXheI1mdnRid3n0bEBQVlhiMEmxNi=> NF24b4kzOjl{OUiwNy=>
1483 M1;RO2Fxd3C2b4Ppd{BCe3O|YYm= MkTWNlAxKG6P NXPlW|NIOjRiaB?= NGftfHRqdmS3Y3WgeIhmKGOnbHygZZBweHSxc3nzJINwNXS{ZXH0cYVvfCC5aYToJG9PYCByOUGy Mo[zNlI6Ojl6MEO=
UMSCC-1 MmL2RZBweHSxc3nzJGF{e3OjeR?= NH\5bFEzODBibl2= M2LwUFI1KGh? MV7pcoR2[2VidHjlJINmdGxiYYDvdJRwe2m|IHPvMZRz\WG2bXXueEB4cXSqIF;OXEAxQTF{ MVyyNlkzQThyMx?=
UMSCC-22A Mn3tS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWL4cYo2UUN3ME2zPE44KMLzIEGuNEBvVQ>? M1HsT|IzQTJ7OECz
UMSCC-22B NHW2c4NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF3OdXRKSzVyPUOwMlchyrFiOT6zJI5O M{D2PFIzQTJ7OECz
1483 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVnqfIttUUN3ME21NE42KMLzIEGxMlkhdk1? MYOyNlkzQThyMx?=
UMSCC-1 M2XabWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXHJR|UxRTN2Lk[gxtEhOi54IH7N MYmyNlkzQThyMx?=
Cal33 M4i1VGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHPYN3ZKSzVyPUS5MlMhyrFiOD65JI5O MWKyNlkzQThyMx?=
PCI-15A MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4TRbmlEPTB;N{CuOEDDuSB{Mj62JI5O NGrIT2QzOjl{OUiwNy=>
PCI-15B M{LwS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWPJR|UxRTN7LkWgxtEhOTFwMDDuUS=> NGfY[|QzOjl{OUiwNy=>
OSC-19 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkLuTWM2OD1zOD6zJOKyKDRwMjDuUS=> MWWyNlkzQThyMx?=
SUDHL16 MYrBdI9xfG:|aYOgRZN{e2G7 MXSyMlAuPC5yIH7N M2\YbFQ5KGh? NGTOR21qdmS3Y3XzJINmdGxiZHXheIgh[29vdILlZZRu\W62IIfpeIghd2KjdH;jcIF5 MUeyNlQyOTh7OR?=
SUDHL16 MWHGeY5kfGmxbjDBd5NigQ>? NFnOc5czNjVibl2= M1jObVI1KGh? MVThZ5RqfmG2ZYOgTm5MNCCrbnHjeIl3[XSnczDBT3QtKHWyLYLl[5Vt[XSnczDOc5hiNCCjbnSgbY5lfWOnczFOt2gzSS6[IHPvMZRz\WG2bXXueEB4cXSqIH;iZZRw[2yjeB?= NUe5W|lOOjJ2MUG4PVk>
Granta MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1GzcVAuPCCwTR?= Mnr6OFghcA>? NU\4RoZKcW6mdXPlJINmdGxiZHXheIgh[29vdILlZZRu\W62IIfpeIghUEGGQ1nz NVzl[YJUOjF5NUCyNlQ>
SUDHL16 NYHuN2hrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlflNU01KG6P M4HnU|M3KGh? NVHrSodYcW6mdXPlJINmdGxiZHXheIgh[29vdILlZZRu\W62IIfpeIghUEGGQ1nz MU[yNFI{Ozl5Mx?=

... Click to View More Cell Line Experimental Data

In vivo Carfilzomib moderately reduces tumor growth in an in vivo xenograft model. Carfilzomib effectively decreases multiple myeloma cell viability following continual or transient treatment mimicking. Carfilzomib increases trabecular bone volume, decreases bone resorption and enhances bone formation in non-tumor bearing mice. [3]

Protocol

Kinase Assay
+ Expand

Enzyme-linked immunosorbent assay for subunit profiling of carfilzomib:

ANBL-6 cells (2 × 106/well) are plated in 96-well plates and treated with Carfilzomib doses from 0.001 to 10 μM for 1 hour. Cells are then lysed (20 mM Tris-HCl, 0.5 mM EDTA), and cleared lysates are transferred to polymerase chain reaction (PCR) plates. A standard curve is generated using untreated ANBL-6 cell lysates starting at a concentration of 6 μg protein/μL. The active site probe [biotin-(CH2)4-Leu-Leu-Leu-epoxyketone; 20 μM] is added and incubated at room temperature for 1 hour. Cell lysates are then denatured by adding 1% sodium dodecyl sulfate (SDS) and heating to 100°C, followed by mixing with 20 μL per well streptavidin-sepharose high-performance beads in a 96-well multiscreen DV plate and incubated for 1 hour. These beads are then washed with enzyme-linked immunosorbent assay (ELISA) buffer (PBS, 1% bovine serum albumin, and 0.1% Tween-20), and incubated overnight at 4°C on a plate shaker with antibodies to proteasome subunits. Antibodies used included mouse monoclonal anti-β1, anti-β2, anti-β1i, and anti-β5i, goat polyclonal anti-β2i, and rabbit polyclonal anti-β5 (affinity-purified antiserum against KLH-CWIRVSSDNVADLHDKYS peptide). The beads are washed and incubated for 2 hours with horseradish peroxidase-conjugated secondary goat antirabbit, goat antimouse or rabbit antigoat antibodies. After washing, the beads are developed using the supersignal ELISA picochemiluminescence substrate. Luminescent detection is performed. Raw luminescence is converted to μg/mL by comparison with the standard curve and expressed as the % inhibition relative to vehicle control. Curve fits are generated using the following nonsigmoidal dose-response equation: Y = Bottom + (Top-Bottom)/(1 + 10̂((LogEC50 − X) × HillSlope)), where X is the logarithm of concentration, Y is the % inhibition, and EC50 is the dose showing 50% effect.
Cell Research
+ Expand
  • Cell lines: WST-1, ANBL-6 cells
  • Concentrations: 100 nM
  • Incubation Time: 1 hour
  • Method: WST-1 is used to determine the effects of proteasome inhibitor Carfilzomib on cell proliferation. The inhibition of proliferation is calculated in relation to parallel control cells that receives vehicle alone. A linear spline function is used to interpolate the median inhibitory concentration (IC50) using XLfit 4 software. The degree of resistance (DOR) is calculated using the formula: DOR = IC50(resistant cells)/IC50(sensitive cells). ANBL-6 cells pulsed with 100 nM carfilzomib are washed and suspended in PBS containing 5 μg/mL of JC-1, which exhibits potential-dependent accumulation in mitochondria. Analysis of the mitochondrial membrane potential-dependent color shift from 525 to 590 nm is carried out on a FacScan, and the data are analyzed with CellQuest software.
    (Only for Reference)
Animal Research
+ Expand
  • Animal Models: Beige-nude-XID mice
  • Formulation: 10% sulfobutylether β-cyclodextrin in 10 mmol/L citrate buffer pH 3.5,
  • Dosages: 2.0 mg/kg
  • Administration: i.v.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 50 mg/mL (69.45 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo 2% DMSO+castor oil 10mg/mL

* 1 mg/ml means slightly soluble or 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 719.91
Formula

C40H57N5O7

CAS No. 868540-17-4
Storage powder
in solvent
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02802163 Not yet recruiting Multiple Myeloma H. Lee Moffitt Cancer Center and Research Institute|Novartis|Amgen September 2016 Phase 1|Phase 2
NCT02756663 Not yet recruiting Multiple Myeloma Novartis Pharmaceuticals|Novartis June 2016 Phase 2
NCT02659293 Recruiting Multiple Myeloma University of Chicago April 2016 Phase 3
NCT02293109 Recruiting Contiguous Stage II Adult Lymphoblastic Lymphoma|Noncontiguous Stage II Adult Lymphoblastic Lymphoma|Stage I Adult Lymphoblastic Lymphoma|Stage III Adult Lymphoblastic Lymphoma|Stage IV Adult Lymphoblastic Lymphoma|Untreated Adult Acute Lymphoblastic Leukemia University of California, Davis|Onyx Pharmaceuticals December 2015 Phase 1
NCT02628704 Not yet recruiting Multiple Myeloma Karyopharm Therapeutics, Inc December 2015 Phase 2
NCT02597062 Recruiting Multiple Myeloma Canadian Cancer Trials Group|Amgen|Myeloma Canada Research Network November 2015 Phase 2

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Frequently Asked Questions

  • Question 1:

    How should I prepare solution of Carfilzomib for ongoing in vivo study?

  • Answer:

    This compound can be dissolved in 2% DMSO/30% PEG 300/dd H2O at 10 mg/ml as a suspension, and can be dissolved in 2% DMSO/ castor oil at 10 mg/ml as a clear solution.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID