Quinoline and thiazolopyridine allosteric inhibitors of MALT1

Bioorg Med Chem Lett. 2019 Jul 15;29(14):1694-1698. doi: 10.1016/j.bmcl.2019.05.040. Epub 2019 May 20.

Abstract

Quinolines and thiazolopyridines were developed as allosteric inhibitors of MALT1, with good cellular potency and exquisite selectivity. Mouse pharmacokinetic (PK) profiling showed these to have low in vivo clearance, and moderate oral exposure. The thiazolopyridines were less lipophilic than the quinolines, and one thiazolopyridine example was active in our hIL10 mouse pharmacodynamic (PD) model upon oral dosing.

Keywords: Allosteric; B-cell lymphomas; MALT1; Protease inhibitors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Humans
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein / antagonists & inhibitors*
  • Quinolines / pharmacology
  • Quinolines / therapeutic use*

Substances

  • Quinolines
  • quinoline
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein