MALT1 inhibitor MI-2
(Synonyms: 2-氯-N-[4-[5-(3,4-二氯苯基)-3-(2-甲氧基乙氧基)-1H-1,2,4-三唑-1-基]苯基]乙酰胺) 目录号 : GC36534
A MALT1 inhibitor
Cas No.:1047953-91-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
MI 2 is an inhibitor of the paracaspase MALT1 with an IC50 value of 5.84 μM in a fluorescence assay.1 It inhibits the growth of MALT1-dependent activated B cell-like diffuse large B cell lymphoma (ABC-DLBCL) cell lines (GI50s = 0.2, 0.5, 0.4, and 0.4 μM for HBL-1, TMD8, OCI-Ly3, and OCI-Ly10 cells, respectively). MI 2 inhibits cleavage of the MALT1 target protein CYLD in a dose-dependent manner in HBL-1 cells but does not inhibit caspase-3, caspase-8, and caspase-9, which are structurally similar to MALT1. MI 2 (25 mg/kg, i.v.) reduces tumor size in TMD8 and HBL-1 mouse xenograft models.
1.Fontan, L., Yang, C., Kabaleeswaran, V., et al.MALT1 small molecule inhibitors specifically suppress ABC-DLBCL in vitro and in vivoCancer Cell.22(6)812-824(2012)
| Cas No. | 1047953-91-2 | SDF | |
| 别名 | 2-氯-N-[4-[5-(3,4-二氯苯基)-3-(2-甲氧基乙氧基)-1H-1,2,4-三唑-1-基]苯基]乙酰胺 | ||
| Canonical SMILES | O=C(NC1=CC=C(N2N=C(OCCOC)N=C2C3=CC=C(Cl)C(Cl)=C3)C=C1)CCl | ||
| 分子式 | C19H17Cl3N4O3 | 分子量 | 455.72 |
| 溶解度 | DMSO: ≥ 46 mg/mL (100.94 mM) | 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1943 mL | 10.9716 mL | 21.9433 mL |
| 5 mM | 0.4389 mL | 2.1943 mL | 4.3887 mL |
| 10 mM | 0.2194 mL | 1.0972 mL | 2.1943 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。
MALT1 Inhibition as a Therapeutic Strategy in T-Cell Acute Lymphoblastic Leukemia by Blocking Notch1-Induced NF-κB Activation
Front Oncol 2020 Sep 23;10:558339.PMID:33072583DOI:10.3389/fonc.2020.558339.
Current treatment of T-cell acute lymphoblastic leukemia (T-ALL) is primarily based on high-intensity combination chemotherapy, which has serious side effects. Therefore, developments of novel targeted therapeutics are urgently needed for treatment of T-ALL. In this study, we found that mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a novel promising therapeutic target for treatment of T-ALL. MALT1 inhibitor MI-2 significantly suppressed the cell growth, proliferation, and colony formation of T-ALL cells. Furthermore, MI-2 induced cell apoptosis of T-ALL via a mitochondrial-dependent pathway. In a T-ALL mouse model, MI-2 significantly reduced leukemic burden and prolonged the survival of leukemia-bearing mice. Mechanistically, MALT1 inhibition effectively blocked both baseline and Notch1-induced activation of nuclear factor κB pathway, which mediates T-ALL cell survival. In conclusion, our results highlight the potential role of MALT1 as an attractive target for treatment of T-ALL and support the potential of MI-2 or other MALT1 inhibitors to clinical trials in T-ALL.
Establishment and characterization of a MALT lymphoma cell line carrying an API2-MALT1 translocation
Genes Chromosomes Cancer 2020 Sep;59(9):517-524.PMID:32348592DOI:10.1002/gcc.22855.
MALT lymphomas with API2(BIRC3)-MALT1 translocation usually have an indolent clinical course and rarely transform into aggressive lymphoma, and there have been no lymphoma cell lines carrying API2-MALT1 translocation reported to date. We established a novel lymphoma cell line named BMA19, carrying the API2-MALT1 translocation from a patient with histologic transformation of intestinal MALT lymphoma. The cells were suggested to carry API2-MALT1 and MYC-IGH translocations by chromosomal analysis, and these translocations were confirmed by polymerase chain reaction analysis. The expression of MYC was shown to be enhanced as a result of the MYC-IGH translocation, and it is considered to have played a role in the histologic transformation of MALT lymphoma. Whole exome sequencing of BMA19 identified several nucleotide variations in genes reported to be mutated in previous studies of marginal zone lymphomas. The MALT1 inhibitor MI-2 specifically decreased cell growth, and the BMA19 cell line was suggested to be still dependent on the API2-MALT1 signal. Subtractive microarray analysis showed that one of the earliest events resulting from MALT1 inhibition is increased susceptibility to endoplasmic reticulum stress-induced apoptosis. The BMA19 cell line is considered to conserve the biological properties of MALT lymphoma and is expected to be a valuable tool for research into the pathogenesis of MALT lymphoma with an API2-MALT1 translocation.