Ixazomib (MLN2238)

製品コードS2180

Ixazomib (MLN2238)化学構造

分子量(MW):361.03

MLN2238 inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50 and Ki of 3.4 nM and 0.93 nM in cell-free assays, respectively, also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites, with IC50 of 31 and 3500 nM. Phase 3.

サイズ 価格(税別)  
In DMSO JPY 43500
JPY 30200
JPY 55100
最寄りの販売代理店を探す

お探しのディーラーが見当たらない場合は直接こちらのメールアドレスまでお問い合わせください:[email protected]

バルク問合せ

製品安全説明書

Proteasome阻害剤の選択性比較

生物活性

製品説明 MLN2238 inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50 and Ki of 3.4 nM and 0.93 nM in cell-free assays, respectively, also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites, with IC50 of 31 and 3500 nM. Phase 3.
特性 A first-in-class proteasome inhibitor that has improved pharmacokinetics (PK), pharmacodynamics(PD), and antitumor activity in preclinical studies.
ターゲット
20S proteasome [1]
(Cell-free assay)
20S proteasome [1]
(Cell-free assay)
0.93 nM(Ki) 3.4 nM
体外試験

At higher concentrations, MLN2238 also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites with IC50 of 31nM and 3.5uM, respectively. MLN2238 inhibits Calu-6 cell with IC50 of 9.7 nM. MLN2238 is a selective, potent, and reversible inhibitor of the proteasome in tumor cells. MLN2238 shows time-dependent reversible proteasome inhibition. Both MLN2238 and Bortezomib shows time-dependent reversible proteasome inhibition; however, the proteasome dissociation half-life for MLN2238 is determined to be ∼6-fold faster than that of Bortezomib (18 and 110 minutes, respectively). MLN2238 dissociates more rapidly from the proteasome than Bortezomib, consistent with faster recovery of proteasome activity observed in the Proteasome-Glo assay. MLN2238 has a greater overall tumor pharmacodynamic effect than Bortezomib as assessed by 20S inhibition. [1]MLN2238 is the biologically active form of MLN9708. [2]

アッセイ
Methods Test Index PMID
Western blot
PARP / Cleaved PARP / Caspase-3 / Cleaved Caspase-3 ; 

PubMed: 27687684     


(a-f) IMR-32 (a) NGP (b) NB-19 (c) SH-SY5Y (d) SK-N-AS (e) and LA-N-6 (f) cells were treated with 10 μM of ixazomib for various time points (0-24 hrs). The cells were then harvested at the end of the treatment, subjected to SDS-PAGE, and immunoblotted with PARP, Caspase-3, and β-actin primary antibodies. β-actin was used as a loading control for whole cell extracts in all samples.

Mcl-1 / Bcl-2 ; 

PubMed: 29348495     


Dose-dependent effects of MLN2238 treatment on Mcl-1 and Bcl-2 expression determined by western blot analysis. Cells exposed to the specified MLN2238 concentrations for 24 h.  

p53 / p21 / NOXA / PUMA / pRb / E2F / Cyclin D1 / CDK6 ; 

PubMed: 21724551     


(D and E) MM.1S cells were treated with MLN2238 (12 nM) for 24h and harvested; protein lysates were subjected to immunoblotting using indicated Abs. (F) MM.1R cells were treated with MLN2238 (12 nM) for 24h and harvested; protein lysates were subjected to immunoblotting using indicated Abs.

27687684 29348495 21724551
Growth inhibition assay
IC50; 

PubMed: 29416618     


The effect of ixazomib in a concentration-dependent manner for 72 h on viability of 28 representative DLBCL cell lines (10 non-GCB subtype and 18 GCB subtype) was assessed. The IC50 value for each cell line was calculated and plotted. * denotes double-hit DLBCL cell lines. 

29416618
体内試験 MLN2238 induces a greater pharmacodynamic response than Bortezomib in xenograft tumors. MLN2238 shows greater maximum and sustained tumor proteasome inhibition compared with Bortezomib in xenograft models. These results confirm that the improved tumor exposure seen with MLN2238 translates into an improved tumor pharmacodynamic response both at the level of and downstream from the proteasome. MLN2238 shows antitumor activity in the CWR22 xenograft model. MLN2238 shows greater tumor pharmacodynamic responses in WSU-DLCL2 xenografts compared with Bortezomib. Similarly, Bortezomib treatment only led to a minor increase in GADD34 levels in WSU-DLCL2 xenograft tumors, whereas MLN2238 strongly induces its expression. [1] MLN2238 has an improved pharmacodynamic profile and antitumor activity compared with Bortezomib in both OCI-Ly10 and PHTX22L models. [2]

お薦めの試験操作(参考用のみ)

キナーゼ試験:[1]
+ 展開

Kinase assay :

Calu-6 cells are cultured in MEM containing 10% fetal bovine serum and 1% penicillin/streptomycin and plated 1 day before the start of the experiment at 1 × 104 cells per well in a 384-well plate. Proteasome activity is assessed by monitoring hydrolysis of the chymotrypsin-like substrate Suc-LLVY-aminoluciferin in the presence of luciferase using the Proteasome-Glo assay reagents according to the manufacturer's instructions. Luminescence is measured using a LEADseeker instrument.
細胞試験: [1]
+ 展開
  • 細胞株: Calu-6 cells
  • 濃度: ~10 nM
  • 反応時間: 1 hour or 30 minutes
  • 実験の流れ: Calu-6 cells are cultured in MEM containing 10% FBS and 1% penicillin/streptomycin and plated 1 day before the start of the experiment at 1 × 104 cells per well in a 384-well plate. For IC50 determinations, cells are treated with varying concentrations of Bortezomib or MLN2238 in DMSO (0.5% final, v/v) for 1 hour at 37 °C. For reversibility experiments, cells are treated with either 1 μM Bortezomib or MLN2238 for 30 minutes at 37 °C and then washed thrice in medium to remove the Bortezomib or MLN2238. Cells are incubated for an additional 4 hours at 37 °C, after which the medium is removed and replaced with fresh medium.
    (参考用のみ)
動物試験:[2]
+ 展開
  • 動物モデル: CB-17 SCID mice are subcutaneously inoculated with MM.1S cells
  • 製剤: Dissolved in 5% 2-hydroxypropyl-β-cyclodextrin
  • 投薬量: 11 mg/kg
  • 投与方法: Twice weekly for 3 weeks (i.v.)
    (参考用のみ)

溶解度 (25°C)

体外 DMSO 72 mg/mL (199.42 mM)
Ethanol 9 mg/mL (24.92 mM)
Water Insoluble
体内 左から(NMPから)右の順に溶剤を製品に加えます(文献ではなく、Selleckの実験によるデータ):
5% DMSO+45% PEG 300+ddH2O
混合させたのち直ちに使用することを推奨します。
17mg/mL

* 溶解度測定はSelleck技術部門によって行われており、その他文献に示されている溶解度と差異がある可能性がありますが、同一ロットの生産工程で起きる正常な現象ですからご安心ください。

化学情報

分子量 361.03
化学式

C14H19BCl2N2O4

CAS No. 1072833-77-2
保管
in solvent
別名 N/A

便利ツール

モル濃度計算器

モル濃度計算器

求めたい質量、体積または濃度を計算してください。

質量 (g) = 濃度 (mol/L) x 体積 (L) x 分子量 (g/mol)

モル濃度計算器方程式

  • 質量
    濃度
    体積
    分子量

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA(製品ページで利用可能な)。

希釈計算器

希釈計算器

貯蔵液を準備するために必要な希釈率を計算してください。Selleck希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 入力 出力 )

  • C1
    V1
    C2
    V2

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA(オンラインで利用できる)で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

  • 連続希釈剤

  • 計算結果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください:

総分子量:g/mol

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

質量 濃度 体積 分子量

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

  • * 必須

Proteasomeシグナル伝達経路

相関Proteasome製品

Tags: Ixazomib (MLN2238)を買う | Ixazomib (MLN2238) ic50 | Ixazomib (MLN2238)供給者 | Ixazomib (MLN2238)を購入する | Ixazomib (MLN2238)費用 | Ixazomib (MLN2238)生産者 | オーダーIxazomib (MLN2238) | Ixazomib (MLN2238)化学構造 | Ixazomib (MLN2238)分子量 | Ixazomib (MLN2238)代理店
×
細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID