Therapeutics: Inducible T cell kinase (ITK)

In vitro and mouse studies suggest tetrahydrindazole-based ITK inhibitors could help treat asthma and other inflammatory diseases. Optimization of a previously identified tetrahydrindazole-based ITK inhibitor (Ki = 0.7 nM) identified a lead analog that bound ITK with a Ki of 0.09 nM and inhibited ITK phosphorylation in a human T cell line with an IC50 of 4 nM, without exhibiting the off-target toxicity observed for the parent compound. In mice with T helper type 2 (Th2) cell stimulation, the lead analog decreased serum levels of Th2-associated pro-inflammatory cytokines compared with vehicle. Next steps could include testing the lead analog in asthma models...