MI-2 (MALT1 inhibitor)

Catalog No.S7429 Batch:S742901

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Technical Data

Formula

C19H17Cl3N4O3
Molecular Weight 455.72 CAS No. 1047953-91-2
Solubility (25°C)* In vitro DMSO 91 mg/mL (199.68 mM)
Ethanol 21 mg/mL (46.08 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description MI-2 (MALT1 inhibitor) is an irreversible MALT1 inhibitor with IC50 of 5.84 μM.
Targets
MALT1 [1]
(cell-free assay)
5.84 μM
In vitro MI-2 inhibits MALT1 functions in ABC-DLBCL cell lines with excellent cell penetration. MI-2 produces selective growth inhibition for MALT1-dependent cell lines with GI50 of 0.2, 0.5, 0.4, and 0.4 礛 in HBL-1, TMD8, OCI-Ly3, and OCI-Ly10 cells, whereas the ABC-DLBCL MALT1-independent cell lines, U2932 and HLY-1, and the two GCB-DLBCL cell lines were resistant. [1]
In vivo MI-2 (350 mg/kg) is nontoxic to mice. MI-2 (25 mg/kg/day i.p.) profoundly suppresses the growth of both the TMD8 and HBL-1 ABC-DLBCL xenografts, whereas it has no effect on the growth of OCI-Ly1 tumors. [1]

Protocol (from reference)

Kinase Assay:[1]
  • High-Throughput Screening for MALT1 Proteolytic Activity Inhibitors

    Ac-LRSR-AMC is used as substrate and reactions are measured with excitation/emission wavelengths of 360/465 nm. Two time points are measured for each reaction to eliminate false positives due to compound autofluorescence. The final percent inhibition is calculated with the formula {[fluorescencetest compound (T2-T1)-fluorescenceneg ctrl (T2-T1)]/[fluorescencepos ctrl (T2-T1)-fluorescenceneg ctrl (T2-T1)]} × 100, where Z-VRPR-FMK (300 nM) is used as positive control and buffer only as negative control. The positive hits are validated in concentration-response experiments within a dose range of 0.122–62.5 µM to determine IC50 of the compounds. Activity is validated using recombinant full-length wild-type MALT1.
Cell Assay:[1]
  • Cell lines

    MALT1-independent cell lines: U2932 and HLY-1, and the two GCB-DLBCL cell lines; MALT1-dependent cell lines: HBL-1, TMD8, OCI-Ly3, and OCI-Ly10 cells.

  • Concentrations

    ~5 μM

  • Incubation Time

    48 hours

  • Method

    Cell proliferation is determined by ATP quantification using a luminescent method and trypan blue dye exclusion. Standard curves for each cell line are calculated by plotting the cell number (determined using trypan blue) against their luminescence values, and cell number is calculated accordingly. Cell viability in drug-treated cells is normalized to their respective controls (fractional viability), and results are given as 1-fractional viability. CompuSyn software is used to determine GI25 and GI50 values.
Animal Study:[1]
  • Animal Models

    SCID NOD.CB17-Prkdcscid/J mice bearing human HBL-1, TMD8, or OCI-Ly1 xenograft.

  • Dosages

    25 mg/kg/day

  • Administration

    i.p.

Customer Product Validation

Data from [Data independently produced by , , Oncogenesis, 2017, 6(7):e365]

Selleck's MI-2 (MALT1 inhibitor) has been cited by 12 publications

Cotargeting of BTK and MALT1 overcomes resistance to BTK inhibitors in mantle cell lymphoma [ J Clin Invest, 2023, 133(3)e165694] PubMed: 36719376
Proteolytic Activity of the Paracaspase MALT1 Is Involved in Epithelial Restitution and Mucosal Healing [ Int J Mol Sci, 2023, 24(8)7402] PubMed: 37108564
Inhibition of Histone H3 Lysine-27 Demethylase Activity Relieves Rheumatoid Arthritis Symptoms via Repression of IL6 Transcription in Macrophages [ Front Immunol, 2022, 13:781364] PubMed: 35296093
MLL1 inhibition reduces IgM levels in Waldenström macroglobulinemia [ Leuk Res, 2022, 116:106841] PubMed: 35462170
Extrinsic interactions in the microenvironment in vivo activate an antiapoptotic multidrug-resistant phenotype in CLL [ Blood Adv, 2021, 5(17):3497-3510] PubMed: 34432864
Inhibition of MALT1 Alleviates Spinal Ischemia/Reperfusion Injury-Induced Neuroinflammation by Modulating Glial Endoplasmic Reticulum Stress in Rats [ J Inflamm Res, 2021, 14:4329-4345] PubMed: 34511971
Copanlisib synergizes with conventional and targeted agents including venetoclax in B- and T-cell lymphoma models. [ Blood Adv, 2020, 4(5):819-829] PubMed: 32126142
Deubiquitinases Maintain Protein Homeostasis and Survival of Cancer Cells upon Glutathione Depletion. [ Cell Metab, 2019, 29(5):1166-1181] PubMed: 30799286
Antiapoptotic properties of MALT1 protease are associated with redox homeostasis in ABC-DLBCL cells. [ Mol Carcinog, 2019, 58(12):2340-2352] PubMed: 31556968
Glutaminolysis Mediated by MALT1 Protease Activity Facilitates PD-L1 Expression on ABC-DLBCL Cells and Contributes to Their Immune Evasion. [ Front Oncol, 2018, 8:632] PubMed: 30619766

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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