Carfilzomib (PR-171) 化学構造
分子量: 719.91

高品質保証

カスタマーフィードバック(3)

MSDS

製品説明

  • Compare Proteasome Inhibitors
    Proteasome製品生物活性の比較
  • 研究分野

製品の説明

生物活性

製品説明 Carfilzomib (PR-171) is a proteasome inhibitor with IC50 less than 5 nM.
ターゲット Proteasome
IC50 5 nM [1]
In vitro試験 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 LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
MM.1S NX;4ZWJ5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnL4NE0yODBibl2= NHj2XYw1QCCq Mn\FTWM2OMLiPdMgNVAhdk1? MUOyOVMyOjV2Mx?=
NCI-H929  M1HE[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1HYeVAuOTByIH7N MWm0PEBp NYnQPIZMUUN3MDC9xsAyPCCwTR?= Mny1NlU{OTJ3NEO=
SUDHL16  MlLURZBweHSxc3nzJGF{e3OjeR?= NF3keHYzNjYkgKOzMlUhdk1? M4OzVlQ5KGh? Mmfu[Y5p[W6lZYOgeIhmKGOnbHyg[IVifGhiY3:teJJm[XSvZX70JJdqfGhiQVPZNVIyPQ>? NHPjUmEzPTJ|OUmzOS=>
SUDHL14 NWLUZ5p5SXCxcITvd4l{KEG|c4PhfS=> MlG3Nk426oDVMz61JI5O NGXhXIg1QCCq NWX3ZmlO\W6qYX7j[ZMhfGinIHPlcIwh\GWjdHigZ48ufHKnYYTt[Y51KHerdHigRWN[OTJzNR?= NH;2NGozPTJ|OUmzOS=>
U2932 NFz2PHNCeG:ydH;zbZMhSXO|c3H5 MkXyNk426oDVMz61JI5O NXnEcVFDPDhiaB?= Mo[w[Y5p[W6lZYOgeIhmKGOnbHyg[IVifGhiY3:teJJm[XSvZX70JJdqfGhiQVPZNVIyPQ>? NFvwZpEzPTJ|OUmzOS=>
P-UMSCC-1 NFva[4lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnjVTWM2OD1zMT6yJI5O M4CzSlI1QTF3MEO5
R-UMSCC-1 M4r1[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUSx[mFFUUN3ME2yNlk1KG6P MYeyOFkyPTB|OR?=
P-Cal33 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFK3TWRKSzVyPUG3MlMhdk1? NVT3ZYZEOjR7MUWwN|k>
R-Cal33 MoniS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1yzTmlEPTB;MUGxNkBvVQ>? M3PycFI1QTF3MEO5
Jurkat MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVWxMVEydk1? NXfYdnh{PDhiaB?= NV;jcHRHcW6qaXLpeJMhfGinIHPlcIwheHKxbHnm[ZJifGmxbjDjc{11emWjdH3lcpQhf2m2aDD2c5Jqdm:|dHH0 M1;zXlI1QDBzMUK4
Jurkat MkfKRZBweHSxc3nzJGF{e3OjeR?= MnO5PEBvVQ>? M2K5TlI1NzR6IHi= NEDvRWtqdmS3Y3XzJIFxd3C2b4Ppd{wh[2G|cHHz[UBi[3SrdnH0bY9vNCCjbnSgVGFTWCClbHXheoFo\SClbz30doVifG2nboSge4l1cCC4b4Lpco9{fGG2 MkPwNlQ5ODFzMki=
UMSCC-22A Ml;XRZBweHSxc3nzJGF{e3OjeR?= NYqxNIhjOjByIH7N NUPWU5pjOjRiaB?= NFPXPIVqdmS3Y3WgeIhmKGOnbHygZZBweHSxc3nzJINwNXS{ZXH0cYVvfCC5aYToJG9PYCByOUGy NX3RSnBFOjJ7Mkm4NFM>
UMSCC-22B NUfZRYhPSXCxcITvd4l{KEG|c4PhfS=> M2LSWlIxOCCwTR?= M4TONlI1KGh? NXXZeYtGcW6mdXPlJJRp\SClZXzsJIFxd3C2b4Ppd{Bkdy22cnXheI1mdnRid3n0bEBQVlhiMEmxNi=> NFmwdmkzOjl{OUiwNy=>
1483 NFnNb4dCeG:ydH;zbZMhSXO|c3H5 MnTsNlAxKG6P MXyyOEBp M{K3OIlv\HWlZTD0bIUh[2WubDDhdI9xfG:|aYOgZ48ufHKnYYTt[Y51KHerdHigU25ZKDB7MUK= NF:2SYozOjl{OUiwNy=>
UMSCC-1 MYnBdI9xfG:|aYOgRZN{e2G7 M2PZ[FIxOCCwTR?= Mle3NlQhcA>? NGrGOJBqdmS3Y3WgeIhmKGOnbHygZZBweHSxc3nzJINwNXS{ZXH0cYVvfCC5aYToJG9PYCByOUGy MnW0NlI6Ojl6MEO=
UMSCC-22A M3TtfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2C1WGlEPTB;M{iuO{DDuSBzLkCgcm0> M1PQW|IzQTJ7OECz
UMSCC-22B M{DrSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NI\6ZpRKSzVyPUOwMlchyrFiOT6zJI5O M{C3NFIzQTJ7OECz
1483 MnntS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGexV3JKSzVyPUWwMlUhyrFiMUGuPUBvVQ>? NYjCb4poOjJ7Mkm4NFM>
UMSCC-1 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1y2ZmlEPTB;M{SuOkDDuSB{Lk[gcm0> Ml;QNlI6Ojl6MEO=
Cal33 M3\1Umdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWjaSXFEUUN3ME20PU4{KMLzIEiuPUBvVQ>? M3LCT|IzQTJ7OECz
PCI-15A NYK5R5NMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIPsdZlKSzVyPUewMlQhyrFiMkKuOkBvVQ>? NYjoOWxZOjJ7Mkm4NFM>
PCI-15B NGPQRWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn7VTWM2OD1|OT61JOKyKDFzLkCgcm0> M1HNPFIzQTJ7OECz
OSC-19 NFWxUI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1H2eGlEPTB;MUiuN{DDuSB2LkKgcm0> NF;5VGwzOjl{OUiwNy=>
SUDHL16 MWjBdI9xfG:|aYOgRZN{e2G7 M1jHSlIvOC12LkCgcm0> Ml\qOFghcA>? NWnRNnZCcW6mdXPld{Bk\WyuIHTlZZRpKGOxLYTy[YF1dWWwdDD3bZRpKG:kYYTvZ4xigA>? NXTLNVY6OjJ2MUG4PVk>
SUDHL16 NWHEVZNQTnWwY4Tpc44hSXO|YYm= MV:yMlUhdk1? MX:yOEBp MkHqZYN1cX[jdHXzJGpPUyxiaX7hZ5RqfmG2ZYOgRWtVNCC3cD3y[Yd2dGG2ZYOgUo95[SxiYX7kJIlv\HWlZYOg{tNJOkFwWDDjc{11emWjdH3lcpQhf2m2aDDvZoF1d2OuYYi= MkSxNlI1OTF6OUm=
Granta NU\h[|hrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHTVcpgxNTRibl2= MlXnOFghcA>? NIHvNYhqdmS3Y3WgZ4VtdCCmZXH0bEBkdy22cnXheI1mdnRid3n0bEBJSUSFSYO= NILqc3AzOTd3MEKyOC=>
SUDHL16 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGjhO4kyNTRibl2= MlzSN|YhcA>? MmnWbY5lfWOnIHPlcIwh\GWjdHigZ48ufHKnYYTt[Y51KHerdHigTGFFS0m| MkO4NlAzOzN7N{O=

... Click to View More Cell Line Experimental Data

In vivo試験 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]
臨床試験 Carfilzomib has entered in a Phase II clinical trial in the treatment of multiple myeloma.
特集

プロトコル (参考用のみ)

キナーゼアッセイ: [1]

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.

細胞アッセイ: [1]

細胞株 WST-1, ANBL-6 cells
濃度 100 nM
反応時間 1 hour
実験の流れ 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.

動物実験: [4]

動物モデル Beige-nude-XID mice
製剤 10% sulfobutylether β-cyclodextrin in 10 mmol/L citrate buffer pH 3.5,
投薬量 2.0 mg/kg
投与方法 i.v.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download Carfilzomib (PR-171) SDF
分子量 719.91
化学式

C40H57N5O7

CAS No. 868540-17-4
保管 3年-20℃
2年-80℃in solvent
別名 N/A
溶解度 (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.
化学名 L-Phenylalaninamide, (αS)-α-[[2-(4-morpholinyl)acetyl]amino]benzenebutanoyl-L-leucyl-N-[(1S)-3-methyl-1-[[(2R)-2-methyl-2-oxiranyl]carbonyl]butyl]-

文献中の引用 (16)

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.

技術サポート&よくある質問(FAQ)

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の質問がある場合は、お気軽くお問合せください。

* 必須

Related プロテアソーム 阻害剤

  • VR23

    VR23は1種の有効なプロテアソーム阻害剤で、トリプシン様プロテアソーム(trypsin-like proteasomes)、キモトリプシン様プロテアソーム(chymotrypsin-like proteasomes)とカスパーゼ様プロテアソーム(caspase-like proteasomes)に作用するIC50値は1 nM、50-100 nMと 3 μMそれぞれに分かれます。

  • Calpeptin

    Calpeptinは1種の有効的で、細胞浸透性のカルパイン( calpain)阻害剤で、カルパインI(豚赤血球)、カルパインII (豚腎臓)、パパイン(Papain)とカルパインI(人血小板)に対するID50値は52 nM、34 nM、138 nMと40 nMそれぞれに分かれます。

  • Marimastat (BB-2516)

    Marimastat (BB-2516)は1種の広範囲に使用されるマトリックスメタロプロテアーゼ(MMP)阻害剤で、MMP-9、MMP-1、MMP-2、MMP-14とMMP-7に作用する IC50値は3 nM、5 nM、6 nM、9 nMと13 nMそれぞれに分かれます。臨床3期。

  • Ledipasvir (GS5885)

    Ledipasvir(GS5885)は1種のHCV NS5Aポリメラーゼ(polymerase)阻害剤で、C型肝炎ウイルス感染の治療に使用します。

  • MG-132

    MG-132は、100nMのIC50によるプロテアソームの強力な阻害剤です。

  • Bortezomib (PS-341)

    Bortezomib (PS-341)は、強力なプロテアソーム阻害剤で、Kiが0.6nMです。

  • Ixazomib (MLN2238)

    Ixazomib (MLN2238)は窒素端加帽の二ペプチドロイシンホウ酸で、20Sプロテアソームのカイモトリプシン類(β5)加水分解部位を抑制、IC50が3.4nM、Ki値が0.93nM。

    Features:A first-in-class proteasome inhibitor that has improved pharmacokinetics (PK), pharmacodynamics(PD), and antitumor activity in preclinical studies.

  • ONX-0914 (PR-957)

    ONX-0914(PR-957)は、恒常的プロテアソームのための最小限の交差反応性を持つ強力かつ選択的な免疫プロテアソームの阻害剤です。

    Features:The first highly selective, small molecule inhibitor of the immunoproteasome. Potential use in cancer and autoimmune diseases (e.g. rheumatoid arthritis, inflammatory bowel disease, and lupus).

  • MLN9708

    MLN9708は二代目経口生物の有効性にプロテアソーム選択阻害剤で、20Sプロテアソームのカイモトリプシン類(β5)加水分解部位に作用すると、IC50が3.4nM、Ki値が0.93nMになる。

    Features:The 1st oral proteasome inhibitor in early stage clinical trials for Multiple Myeloma.

最近チェックしたアイテム

Tags: Carfilzomib (PR-171)を買う | Carfilzomib (PR-171)供給者 | Carfilzomib (PR-171)を購入する | Carfilzomib (PR-171)費用 | Carfilzomib (PR-171)生産者 | オーダーCarfilzomib (PR-171) | Carfilzomib (PR-171)代理店
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
お問い合わせ