PAD2-IN-1 hydrochloride, a benzimidazole-based derivative, is a potent and selective protein arginine deiminase 2 (PAD2) inhibitor. PAD2-IN-1 hydrochloride shows superior selectivity for PAD2 over PAD4 (95-fold) and PAD3 (79-fold)[1].
In the target engagement assay, the EC 50 of PAD2-IN-1 (compound 32a) hydrochloride is 8.3 μM in HEK293T/PAD2 cells, the enhanced potency of PAD2-IN-1 overcomes its relatively poor ability to enter cells[1].
PAD2-IN-1 (compound 32a; 1-25 μM) hydrochloride treatment strongly inhibits histone H3 citrullination with an EC 50 of 2.7 μM in HEK293T/PAD2 cells[1].