@article{ae77a785d3a346048ae809b797495e18,
title = "Peptide-based covalent inhibitors of MALT1 paracaspase",
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.",
keywords = "Covalent, Inhibitors, Peptide, Protease",
author = "Hatcher, {John M.} and Guangyan Du and Lorena Font{\'a}n and Ilkay Us and Qi Qiao and Spandan Chennamadhavuni and Jay Shao and Hao Wu and Ari Melnick and Gray, {Nathanael S.} and Scott, {David A.}",
note = "Funding Information: Compounds 27, 30, 45, 52 and 53 were prepared by Peptech Corporation, under the chemistry leadership of Hongyan Liu. Microsome and plasma stability experiments, and mouse PK studies, were conducted at the Drug Metabolism and Pharmacokinetics laboratory at The Scripps Research Institute, under the supervision of Mike Cameron. Protease profiling was conducted at Genscript USA. This work was supported by funding from Janssen Pharmaceuticals and the NIH ( R01 CA182736 ). Funding Information: Compounds 27, 30, 45, 52 and 53 were prepared by Peptech Corporation, under the chemistry leadership of Hongyan Liu. Microsome and plasma stability experiments, and mouse PK studies, were conducted at the Drug Metabolism and Pharmacokinetics laboratory at The Scripps Research Institute, under the supervision of Mike Cameron. Protease profiling was conducted at Genscript USA. This work was supported by funding from Janssen Pharmaceuticals and the NIH (R01 CA182736). Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",
year = "2019",
month = jun,
day = "1",
doi = "10.1016/j.bmcl.2019.03.046",
language = "English (US)",
volume = "29",
pages = "1336--1339",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "11",
}