BPK-25, an active acrylamide, promotes degradation of nucleosome remodeling and deacetylation (NuRD) complex proteins by a post-translational mechanism involving covalent protein engagement. BPK-25 inhibits TMEM173 activation by the cyclic dinucleotide ligand cGAMP[1].

BPK-25 (10 μM; 5 hours) inhibits TMEM173 activation by the cyclic dinucleotide ligand cGAMP[1]. BPK-25 (10 μM; 24 hours) suppresses NF-κB activation blocks nuclear factor of activated T-cells (NFAT) activation, as measured by >50% reductions in IκBα phosphorylation[1]. BPK-25 (10 μM; 4 hours) also reduces NFATc2 expression in T cells[1]. BPK-25 (0.1, 1, 5, 10, 20 μM; 24 hours) promotes the striking and selective reduction of several proteins in the nucleosome remodeling and deacetylation (NuRD) complex in a concentration- and time-dependent manner. BPK-25 does not have corresponding changes in mRNA expression[1]. A non-electrophilic propanamide analog of BPK-25 (BPK-25-ctrl) does not suppress T cell activation or affect NuRD complex proteins in T cells[1].

[1]. Ekaterina V Vinogradova, et al. An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells. Cell. 2020 Aug 20;182(4):1009-1026.e29.