5.00491

MALT1 Inhibitor I, MI-2

• Synonym(s): MALT1 Inhibitor I, MI-2, ALB-H03200218, 2-Chloro-N-(4-(5-(3,4-dichlorophenyl)-3-(2-methoxyethoxy)-1H-1,2,4-triazol-1-yl)phenyl)acetamide
• Empirical Formula (Hill Notation): C₁₉H₁₇Cl₃N₄O₃
• CAS Number: 1047953-91-2
• Molecular Weight: 455.72
• UNSPSC Code: 12352200
• PubChem Substance ID: 45942672
• Assay: ≥97% (HPLC)
• Form: solid
• Storage condition: OK to freeze, desiccated, protect from light

Properties

• assay: ≥97% (HPLC)
• Quality Segment: 100
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze, desiccated, protect from light
• color: beige
• solubility: DMSO: 50 mg/mL
• storage temp.: −20°C
• SMILES string: COCCOC1=NN(C(=N1)C2=CC(=C(C=C2)Cl)Cl)C3=CC=C(C=C3)NC(=O)CCl

Description

General description

A cell-permeable chloromethyl amide that inhibits MALT1 proteolytic activity (IC₅₀ = 5.84 µM against MALT1 paracaspase domain dimer-catalyzed Ac-LRSR-AMC hydrolysis) in an irreversible manner via covalent interaction, displaying little or no activity against caspase-3, -8, or -9. Due to irreversible binding and effective intracellular accumulation (HBL-1 intracellular [MI-2]_{t = 2 h} = 5 µM; Medium [MI-2]_{t = 0} = 0.2 µM), MI-2 is at least 250-times more effective than Z-VRPR-FMK in blocking constitutive NF-κB activity and c-Rel nuclear translocation in HBL-1 cultures (equal or better blockage by 200 nM MI-2 than by 50 µM Z-VRPR-FMK). Shown to selectively inhibit MALT1-dependent ABC-DLBCL proliferation, but not the MALT1-independent growths of ABC- (HLY-1 and U2932) or GCB-DLBCL (OCI-Ly1 and OCI-Ly7) cells, both in cultures in vitro (GI₅₀ in 48 h = 200, 400, 400, and 500 nM, respectively, against HBL-1, OCI-Ly3, OCI-Ly10, and TMD8) and in mice in vivo (65%,, 61%, and 0% suppression, respectively, of HBL-1, TMD8, and OCI-Ly1 tumor expansion 24 h after 14 daily 25 mg/kg/day i.p. dosages) without any apparent toxicity to mice.

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
MALT1

Reversible: no

Packaging

Packaged under inert gas

Preparation Note

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Use only fresh DMSO for reconstitution.

Other Notes

Fontan, L., et al. 2012. Cancer Cell22, 812.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Disclaimer

Toxicity: Standard Handling (A)

Safety Information

• Storage Class: 11 - Combustible Solids
• WGK: WGK 2
• Flash Point (°F): Not applicable
• Flash Point (°C): Not applicable