A cell-permeable phenothiazine that that inhibits MALT1, but not caspase-3 or -8, proteolytic activity (IC50 = 0.83 and 0.42uM, 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 10uM; IC50 <5uM 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 10uM) over GCB-DLBCL (≤26% cell death in 4 days at 20uM) both in cultures in vitro and in mice (400ug/kg daily i.p.) in vivo.
Synonyms: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 tissue Lymphoma Translocation 1 Inhibitor II, Pacatal
Solubility:DMSO or H2O
Molecular Formula:C₁₉H₂₃ClN₂S • x HCl
NMR:Conforms
Carbon:As Reported
Hydrogen:As Reported
Nitrogen:As Reported
Sulfur:As Reported
LC-MS:As Reported
Water by CHN (mol):As Reported
Storage and Stability:Lyophilized powder may be stored at -20°C. Stable for 6 months after receipt at -20°C. Reconstitute with sterile buffer or ddH2O. Aliquot to avoid repeated freezing and thawing. Store at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
