Ixazomib (MLN2238)

製品コード：S2180 純度：99.88%

Ixazomib (MLN2238) inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50 and K_i 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. Ixazomib (MLN2238) induces autophagy. Phase 3.

CAS No. 1072833-77-2

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 37500	国内在庫あり
5mg	JPY 25500	国内在庫あり
10mg	JPY 48000	国内在庫あり
50mg	JPY 145500	国内在庫あり
1g	JPY 1048500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（64）

製品安全説明書

現在のバッチを見る：純度： 99.88%

99.88

Ixazomib (MLN2238)関連製品

関連ターゲット	20S proteasome	もっと見る
関連製品	MG132 Epoxomicin (BU-4061T) Celastrol Oprozomib ONX-0914 (PR-957) Delanzomib VR23 Marizomib (Salinosporamide A) PI-1840	もっと見る
関連化合物ライブラリー	FDA-approved Drug Library Natural Product Library Bioactive Compound Library-I Protease Inhibitor Library Ubiquitination Compound Library	もっと見る

シグナル伝達経路

Proteasomeシグナル伝達経路

Proteasome阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Incubation Time	活性情報	PMID
HEK293	Function assay	1 hr	Inhibition of NFkappaB in HEK293 cells incubated for 1 hr prior to TNF-alpha challenge measured after 3 hrs by luciferase reporter gene assay relative to control, IC50 = 0.0062 μM.	ChEMBL
Calu6	Function assay	1 hr	Inhibition of 26S proteasome beta5 subunit in human Calu6 cells using Suc-LLVY-aminoluciferin as substrate after 1hr by luminescence assay, IC50 = 0.009 μM.	ChEMBL
Calu6	Cytotoxicity assay	72 hrs	Cytotoxicity against human Calu6 cells after 72 hrs by luminescence assay, LC50 = 0.014 μM.	ChEMBL
U266B1	Cytotoxicity assay	72 hrs	Cytotoxicity against human U266B1 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay, IC50 = 0.05215 μM.	29934218
RPMI8226	Cytotoxicity assay	72 hrs	Cytotoxicity against human RPMI8226 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay, IC50 = 0.05532 μM.	29934218
ARH77	Cytotoxicity assay	72 hrs	Cytotoxicity against human ARH77 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay, IC50 = 0.0655 μM.	29934218
TC32	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
U-2 OS	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	29435139
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
Saos-2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
SK-N-SH	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
MG 63 (6-TG R)	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
OHS-50	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells	29435139
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
fibroblast cells	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells	29435139
SK-N-SH	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
Rh30	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells	29435139
U-2 OS	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells	29435139
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells	29435139
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells	29435139
SJ-GBM2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
SK-N-MC	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
NB-EBc1	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
LAN-5	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
Rh18	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
SJ-GBM2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells	29435139
Rh18	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells	29435139
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生物活性

製品説明

特性

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

Targets

20S proteasome ^[1] (Cell-free assay)	20S proteasome ^[1] (Cell-free assay)
0.93 nM(Ki)	3.4 nM

In Vitro
In vitro	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]
Kinase Assay	Kinase assay
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.
細胞実験	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.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	PARP / Cleaved PARP / Caspase-3 / Cleaved Caspase-3 Mcl-1 / Bcl-2 p53 / p21 / NOXA / PUMA / pRb / E2F / Cyclin D1 / CDK6		27687684
	Growth inhibition assay	IC50		29416618

In Vivo
In Vivo	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]
動物実験	動物モデル	CB-17 SCID mice are subcutaneously inoculated with MM.1S cells
	投与量	11 mg/kg
	投与経路	Twice weekly for 3 weeks (i.v.)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT00963820	Completed	Multiple Myeloma	Millennium Pharmaceuticals Inc.\|Takeda	October 2009	Phase 1

参考
[1] Kupperman E, et al. Cancer Res, 2010, 70(5), 1970-80 [2] Lee EC, et al. Clin Cancer Res, 2011, 17(23), 7313-23.

参考

化学情報

分子量	361.03	化学式	C₁₄H₁₉BCl₂N₂O₄
CAS No.	1072833-77-2	SDF	Download Ixazomib (MLN2238) SDFをダウンロードする
Smiles	B(C(CC(C)C)NC(=O)CNC(=O)C1=C(C=CC(=C1)Cl)Cl)(O)O
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	１ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 72 mg/mL ( (199.42 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 72 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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