5.00500

MALT1 Inhibitor II, Mepazine Hydrochloride

• Synonym(s): MALT1 Inhibitor II, Mepazine Hydrochloride, 10-((1-Methylpiperidin-3-yl)methyl)-10H-phenothiazine, Hydrochloride, 10-((1-Methyl-3-piperidyl)methyl)phenothiazine, Hydrochloride, 10-((1-Methyl-3-piperidinyl)methyl)-10H-phenothiazine, Hydrochloride, MALT-1 Inhibitor II, Mucosa-Associated Lymphoid tis
• Empirical Formula (Hill Notation): C₁₉H₂₃ClN₂S
• CAS Number: 2975-36-2
• Molecular Weight: 346.92

Properties

• Assay: ≥97% (HPLC)
• Quality Level: 100
• form: powder
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; desiccated (hygroscopic); protect from light
• color: gray to off-white
• solubility: H₂O: 2.5 mg/mL; DMSO: 25 mg/mL
• storage temp.: −20°C
• InChI: 1S/C19H22N2S.Cl/c1-20-12-6-7-15(13-20)14-21-16-8-2-4-10-18(16)22-19-11-5-3-9-17(19)21;/h2-5,8-11,15H,6-7,12-14H2,1H3;
• InChI key: ZGQUIYCUOPQIDJ-UHFFFAOYSA-N

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.

A cell-permeable phenothiazine that 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-catalyzed Ac-LRSR-AMC hydrolysis) in a reversible and noncompetitive manner. Shown to suppress ABC-DLBCL constitutive cellular MALT1 activity (by >75% at 10 µM; IC₅₀<5 µM in U2932, OCI-Ly10, OCI-Ly3, HBL1, and TMD8 cultures) and RelB cleavage, resulting in ABC-DLBCL-selective cytotoxicity (≥27% cell death in 4 days at 10 µM) over GCB-DLBCL (≤26% cell death in 4 days at 20 µM) both in cultures in vitro and in mice (400 µg/kg daily i.p.) in vivo.

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.

MALT1 Inhibitor II, Mepazine HCl, CAS 60-89-9, is a cell-permeable inhibitor of MALT1. Does not affect caspase-3 or -8 activities.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
MALT1

Warning

Toxicity: Standard Handling (A)

Physical form

Supplied as a hydrochloride salt.

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Other Notes

Schlauderer, F., et al. 2013. Angew. Chem. Int. Ed.52, In press.
Nagel, D., et al. 2012. Cancer Cell22, 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