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MLN2238 Sale

(Synonyms: 艾沙佐米; MLN2238) 目录号 : GC16146

A 20S proteasome inhibitor and an active metabolite of MLN9708

MLN2238 Chemical Structure

Cas No.:1072833-77-2

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥694.00
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5mg
¥540.00
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10mg
¥810.00
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50mg
¥2,657.00
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100mg
¥3,580.00
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Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

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实验参考方法

Kinase experiment [1]:

Kinase assay

Calu-6 cells were 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 was 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 was measured using a LEADseeker instrument.

Cell experiment [1]:

Cell lines

Calu-6 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℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reaction Conditions

≤ 10 nM; 1 hr

Applications

MLN2238 inhibited Calu-6 cells with an IC50 value of 9.7 nM.

Animal experiment [2]:

Animal models

DP54-Luc tumor-bearing NOD-SCID mice

Dosage form

11 mg/kg; i.v.; twice weekly for 17 consecutive days

Applications

Both Bortezomib and MLN2238 reduced tumor burden (T/C = 0.48 and 0.22, respectively).

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]. Kupperman E, Lee EC, Cao Y, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Research, 2010, 70 (5): 1970-80.

[2]. Lee EC, Fitzgerald M, Bannerman B, et al. Antitumor Activity of the Investigational Proteasome Inhibitor MLN9708 in Mouse Models of B-cell and Plasma Cell Malignancies. CLINICAL CANCER RESEARCH, 2011, 17 (23): 7313-7323.

产品描述

MLN2238 is a potent reversible inhibitor that inhibits specific β5 site of the 20S proteasome with IC50 value of 3.4 nM and Ki value of 0.93 nM.[1]    
MLN2238, an N-capped dipeptidyl leucine boronic acid , preferentially bound to and inhibited the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with an IC50 value of 3.4 nM (Ki value of 0.93 nM). As the concentration increased, it also inhibited the caspase-like (β1) with IC50 value of 31 nM and trypsin-like (β2) proteolytic sites with IC50 value of 3,500 nM. The clinical studies in the model of both solid-tumor and hematological xenograft have demonstrated preclinical antitumor activity. Comparing to bortezomib, MLN2238 showed the activity in pharmacokinetics, pharmacodynamics and antitumor. It is believed that the activation of caspases, the p53 pathway, and endoplasmic reticulum stress and inhibition of NF-κB are related to MLN2238-induced MM cell death. [1,2]        
MLN2238 inhibited growth and triggers apoptosis in MM cells resistant to conventional and bortezomib therapies without affecting the viability of normal cells [2]. MLN2238 has significant cytotoxic activity in RSCL and RRCL preclinical models. Although BTZ and MLN2238 have similar reversible proteasome inhibition, the proteasome dissociation half-life (t1/2) of MLN2238 was found to be approximately sixfold faster than BTZ (t1/2 of 18 vs. 110min, respectively) while has the similar LD50 values to BTZ in a variety of cultured mammalian cancer cell lines. MLN2238 is approximately two to three times more potent than BTZ in lymphoma cell models. The IC50 of MLN2238 was 2.5 nmol/l in contrast to 7.5nmol/l of BTZ in Raji parental cells. [3]
In many mouse models of hematologic malignancies, such as tumor xenograft models which derived from a human lymphoma cell line and primary human lymphoma tissue, and genetically engineered mouse models of plasma cell malignancies, the result showed the antitumor activity of MLN2238.[4]
References:
1.Kupperman E, Lee EC, Cao Y, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Research, 2010, 70 (5): 1970-80.
2.Tian Z, Zhao J, Tai Y, et al. Investigational agent MLN9708/2238 targets tumor-suppressor miR33b in MM cells. Blood, 2012, 120 (19): 3958-3967
3.Gu JJ,  Hernandez-Ilizaliturri FJ, Mavis C, et al. MLN2238, a proteasome inhibitor, induces caspase-dependent cell death, cell cycle arrest, and potentiates the cytotoxic activity of chemotherapy agents in rituximab-chemotherapy-sensitive or rituximab-chemotherapy-resistant B-cell lymphoma preclinical models. ANTI-CANCER DRUGS, 2013, 24 (10): 1030-1038.
4.Lee EC, Fitzgerald M, Bannerman B, et al. Antitumor Activity of the Investigational Proteasome Inhibitor MLN9708 in Mouse Models of B-cell and Plasma Cell Malignancies. CLINICAL CANCER RESEARCH, 2011, 17 (23): 7313-7323.

Chemical Properties

Cas No. 1072833-77-2 SDF
别名 艾沙佐米; MLN2238
化学名 [(1R)-1-[[(2S,3R)-3-hydroxy-2-[(6-phenylpyridine-2-carbonyl)amino]butanoyl]amino]-3-methylbutyl]boronic acid
Canonical SMILES B(C(CC(C)C)NC(=O)CNC(=O)C1=C(C=CC(=C1)Cl)Cl)(O)O
分子式 C14H19BCl2N2O4 分子量 361
溶解度 ≥ 16.8 mg/mL in DMSO, ≥ 103 mg/mL in EtOH with ultrasonic 储存条件 Store at -20°C
General tips 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。
储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。
Shipping Condition 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。

溶解性数据

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1 mg 5 mg 10 mg
1 mM 2.7701 mL 13.8504 mL 27.7008 mL
5 mM 0.554 mL 2.7701 mL 5.5402 mL
10 mM 0.277 mL 1.385 mL 2.7701 mL
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