Chemical Probes for Profiling of MALT1 Protease Activity

Chembiochem. 2023 Nov 2;24(21):e202300444. doi: 10.1002/cbic.202300444. Epub 2023 Sep 15.

Abstract

The paracaspase MALT1 is a key regulator of the human immune response. It is implicated in a variety of human diseases. For example, deregulated protease activity drives the survival of malignant lymphomas and is involved in the pathophysiology of autoimmune/inflammatory diseases. Thus, MALT1 has attracted attention as promising drug target. Although many MALT1 inhibitors have been identified, molecular tools to study MALT1 activity, target engagement and inhibition in complex biological samples, such as living cells and patient material, are still scarce. Such tools are valuable to validate MALT1 as a drug target in vivo and to assess yet unknown biological roles of MALT1. In this review, we discuss the recent literature on the development and biological application of molecular tools to study MALT1 activity and inhibition.

Keywords: activity-based probes; diffuse large B-cell lymphoma; fluorescent substrates; mucosa-associated lymphoid tissue protein 1.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmune Diseases*
  • Caspases* / metabolism
  • Humans
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • NF-kappa B
  • Proteolysis

Substances

  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • Caspases
  • NF-kappa B
  • MALT1 protein, human