Inflammation

Mouse studies identified a dithiolo[3,4-c]quinolinylidene-based TAGLN2 agonist that could help treat asthma. Virtual screening of a small molecule library against TAGL2 and chemical synthesis of hits yielded a dithiolo[3,4-c]quinolinylidene analog that bound to TAGLN2 with a K_d of 11 nM. In a rat airway smooth muscle cell-based assay of acetylcholine-induced contraction, the compound inhibited contraction in wild-type cells with an EC₅₀ of 6.8 nM but had no effect in TAGLN-knockout cells. In mouse models of ovalbumin- and house dust mite-induced asthma, the compound decreased pulmonary resistance compared with the generic adrenergic receptor β2 (ADRB2) agonists terbutaline and isoproterenol or an inactive control compound. Next steps could include testing the compound in additional models of asthma.

Terbutaline is marketed to treat asthma...