Submitted by jup2017 on May 14, 2019 - 8:22am
| Title | Peptide-based covalent inhibitors of MALT1 paracaspase. |
| Publication Type | Journal Article |
| Year of Publication | 2019 |
| Authors | Hatcher, John M., Du Guangyan, Fontan Lorena, Us Ilkay, Qiao Qi, Chennamadhavuni Spandan, Shao Jay, Wu Hao, Melnick Ari, Gray Nathanael S., and Scott David A. |
| Journal | Bioorg Med Chem Lett |
| Volume | 29 |
| Issue | 11 |
| Pagination | 1336-1339 |
| Date Published | 2019 Jun 01 |
| ISSN | 1464-3405 |
| Keywords | Caspase Inhibitors, Dose-Response Relationship, Drug, Humans, Molecular Structure, Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein, Peptides, Structure-Activity Relationship |
| Abstract | <p>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.</p> |
| DOI | 10.1016/j.bmcl.2019.03.046 |
| Alternate Journal | Bioorg Med Chem Lett |
| PubMed ID | 30954428 |
| Grant List | R01 AI050872 / AI / NIAID NIH HHS / United States R01 CA182736 / CA / NCI NIH HHS / United States |