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Updated: Jan 26, 2026

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
Peptide-based covalent inhibitors of MALT1 paracaspase
John M Hatcher1, Guangyan Du1, Lorena Fontán2
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, 360 Longwood Ave, Boston, MA 02115, USA.
Abstract:
Potent and selective substrate-based covalent inhibitors of MALT1 protease were developed from the tetrapeptide tool compound Z-VRPR-fmk. To improve cell permeability, we replaced one arginine residue. We further optimized a series of tripeptides and identified compounds that were potent in both a GloSensor reporter assay measuring cellular MALT1 protease activity, and an OCI-Ly3 cell proliferation assay. Example compounds showed good overall selectivity towards cysteine proteases, and one compound was selected for further profiling in ABL-DLBCL cells and xenograft efficacy models.
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