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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Development of new Malt1 inhibitors and probes.
Bioorg. Med. Chem. 24, 3312-3329 (2016)
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (Malt1) is a promising therapeutic target for the treatment of activated B cell-like diffuse large B cell lymphoma (ABC-DLBCL). Several research groups have reported on the development of Malt1 inhibitors and activity-based probes for in vitro and in situ monitoring and modulating Malt1 activity. In this paper, we report on two activity-based Malt1 probes (6 and 7) and a focused library of 19 new Malt1 inhibitors. Our peptide-based probe 6 labels Malt1 in an activity-based manner. In contrast, probe 7, derived from the known covalent inhibitor MI-2, labels both wild type and catalytically inactive Cys to Ala mutant Malt1, suggesting that MI-2 inhibits Malt1 by reacting with a nucleophilic residue other than the active site cysteine. Furthermore, two of our inhibitors (9, apparent IC50 3.0μM, and 13, apparent IC50 2.1μM) show good inhibitory activity against Malt1 and outperform MI-2 (apparent IC50 7.8μM) in our competitive activity-based protein profiling assay.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Activity-based Protein Profiling ; Lymphoma ; Malt1 ; Malt1 Inhibitors ; Mechanism-based Inhibitor; T-cell-activation; Paracaspase Malt1; Abc-dlbcl; Lymphoma; Metacaspases; Cleavage; Protease; Key
ISSN (print) / ISBN
0968-0896
e-ISSN
1464-3391
Zeitschrift
Bioorganic and Medicinal Chemistry
Quellenangaben
Band: 24,
Heft: 15,
Seiten: 3312-3329
Verlag
Elsevier
Verlagsort
Oxford
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Research Unit Signaling and Translation (SAT)