Inhibition of c-Rel DNA binding is critical for the anti-inflammatory effects of novel PIKfyve inhibitor.

Aberrant production of proinflammatory cytokines is linked to many autoimmune diseases, and their inhibition by small molecule compounds is considered beneficial. Here, we performed phenotypic screening in IFNγ/LPS-activated RAW264.7, mouse macrophage cells, and discovered AS2677131 and AS2795440 as novel and potent inhibitors of IL-12p40, a subunit of IL-23.

Anti-inflammatory effect and selectivity profile of AS1940477, a novel and potent p38 mitogen-activated protein kinase inhibitor.

Given the key role p38 mitogen-activated protein kinase (MAPK) plays in inflammatory responses through the production of cytokines and inflammatory mediators, its inhibition is considered a promising therapeutic strategy for chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, inflammatory bowel disease, and chronic obstructive pulmonary disease. Here, we evaluated the anti-inflammatory effect and selectivity profile of the novel p38 MAPK inhibitor AS1940477. AS1940477 inhibited the enzymatic activity of recombinant p38α and β isoforms but showed no effect against other 100 protein kinases including p38γ and δ isoforms.

Mammalian chromatin remodeling complex SWI/SNF is essential for enhanced expression of the albumin gene during liver development.

The chromatin remodeling complex SWI/SNF is known to regulate the transcription of several genes by controlling chromatin structure in an ATP-dependent manner. SWI/SNF contains the Swi2p/Snf2p like ATPases BRG1 or BRM exclusively. We found that the expression of BRM gradually increases and that of BRG1 decreases as liver cells differentiate.

Repression of GR-mediated expression of the tryptophan oxygenase gene by the SWI/SNF complex during liver development.

The chromatin remodeling complex, SWI/SNF, is known to regulate the transcription of several genes by altering the chromatin structure in an ATP-dependent manner. SWI/SNF exclusively contains BRG1 or BRM as an ATPase subunit. In the present study, we studied the role of SWI/SNF containing BRM or BRG1 in the expression of the liver-specific tryptophan oxygenase (TO) and tyrosine aminotransferase genes.