5.34330

MALT1 Inhibitor III, Mepazine Acetate

• Synonym(s): MALT1 Inhibitor III, Mepazine Acetate, Pacatal, 10-((1-Methyl-3-piperidinyl)methyl)-10H-phenothiazine, Acetate, Mucosa-Associated Lymphoid tissue Lymphoma Translocation 1 Inhibitor III, MALT-1 Inhibitor III
• Empirical Formula (Hill Notation): C₁₉H₂₂N₂S · xC₂H₄O₂
• Molecular Weight: 310.46 (free base basis)

Properties

• assay: ≥95% (HPLC)
• Quality Level: 100
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; desiccated (hygroscopic); protect from light
• color: purple
• solubility: DMSO: 100 mg/mL; water: 50 mg/mL
• storage temp.: −20°C

Description

General description

A cell-permeable phenothiazine that inhibits MALT1, but not caspase-3 or -8, proteolytic activity (IC₅₀ = 0.83 and 0.42 µM, respectively, against full-length or paracaspase domain-containing aa 325-760 MALT1 GST fusion-catalyzed Ac-LRSR-AMC hydrolysis) in a reversible and noncompetitive manner and blocks anti-CD3/CD28-stimulated IL-6 production (20 h) in primary murine CD4⁺ T-cell (by 77%) and human PBMC cultures (by 51 - 89%). Shown to suppress ABC-DLBCL constitutive cellular MALT1 activity (>75% suppression by 10 µM Mepazine; IC₅₀<5 µM in U2932, OCI-Ly10, OCI-Ly3, HBL1, and TMD8 cultures) and RelB cleavage, resulting in effective blockage of NF-κB-dependent IL-6, IL-10, as well as anti-apoptotic Bcl-x_L and FLIP-L expressions. Mepazine exhibits ABC-DLBCL-selective cytotoxicity (≥27% cell death in 4 days by 10 µM Mepazine in HBL-1, OCI-Ly3, OCI-Ly10, TMD8, and U2932 cultures) over GCB-DLBCL (≤26% cell death in 4 days by 20 µM Mepazine in DJAB, Su-DHL-4, and Su-DHL-6 cultures) both in cultures in vitro and in mice (74%, and 0% suppression, respectively, of OCI-Ly10 and Su-DHL-6 tumor expansion on day 22 post cancer transplant; via daily 400 µg/kg i.p.) in vivo.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
MALT1

Reversible: yes

Target IC₅₀: 0.83 and 0.42 &micro

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

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

Other Notes

Schlauderer, F., et al. 2013. Angew. Chem. Int. Ed.52, 10384.
Nagel, D., et al. 2012. Cancer Cell.22, 825.

Legal Information

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

Safety Information

• Pictograms: GHS07
• Signal Word: Warning
• Hazard Statements: H302
• Precautionary Statements: P264 - P270 - P301 + P312 - P501
• Hazard Classifications: Acute Tox. 4 Oral
• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable