821768-09-6Relevant articles and documents
Discovery and optimization of a series of small-molecule allosteric inhibitors of MALT1 protease
Lu, Tianbao,Connolly, Peter J.,Philippar, Ulrike,Sun, Weimei,Cummings, Maxwell D.,Barbay, Kent,Gys, Luc,Van Nuffel, Luc,Austin, Nigel,Bekkers, Mariette,Shen, Fang,Cai, Ann,Attar, Ricardo,Meerpoel, Lieven,Edwards, James
, (2019/11/11)
We describe a series of potent and highly selective small-molecule MALT1 inhibitors, optimized from a High-Throughput Screening hit. Advanced analogues such as compound 40 show high potency (IC50: 0.01 μM) in a biochemical assay measuring MALT1 enzymatic activity, as well as in cellular assays: Jurkat T cell activation (0.05 μM) and IL6/10 secretion (IC50: 0.10/0.06 μM) in the TMD8 B-cell lymphoma line. Compound 40 also inhibited cleavage of the MALT1 substrate RelB (IC50: 0.10 μM). Mechanistic enzymology results suggest that these compounds bind to the known allosteric site of the protease.
Identification and biological evaluation of 4-(3-trifluoromethylpyridin-2- yl)piperazine-1-carboxylic acid (5-trifluoromethylpyridin-2-yl)amide, a high affinity TRPV1 (VR1) vanilloid receptor antagonist
Swanson, Devin M.,Dubin, Adrienne E.,Shah, Chandra,Nasser, Nadia,Chang, Leon,Dax, Scott L.,Jetter, Michele,Breitenbucher, J. Guy,Liu, Changlu,Mazur, Curt,Lord, Brian,Gonzales, Lisa,Hoey, Kenway,Rizzolio, Michele,Bogenstaetter, Michael,Codd, Ellen E.,Lee, Doo H.,Zhang, Sui-Po,Chaplan, Sandra R.,Carruthers, Nicholas I.
, p. 1857 - 1872 (2007/10/03)
High throughput screening using the recombinant human TRPV1 receptor was used to identify a series of pyridinylpiperazine ureas (3) as TRPV1 vanilloid receptor ligands. Exploration of the structure-activity relationships by parallel synthesis identified t
