MLN2238
(Synonyms: 艾沙佐米; MLN2238) 目录号 : GC16146A 20S proteasome inhibitor and an active metabolite of MLN9708
Cas No.:1072833-77-2
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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. |
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.
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。 |
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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。 |
制备储备液 | |||
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 |
第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量) | ||||||||||
给药剂量 | mg/kg | 动物平均体重 | g | 每只动物给药体积 | ul | 动物数量 | 只 | |||
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方) | ||||||||||
% DMSO % % Tween 80 % saline | ||||||||||
计算重置 |
计算结果:
工作液浓度: mg/ml;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL,
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL saline,混匀澄清。
1. 首先保证母液是澄清的;
2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。