1 research outputs found
Identification of a Novel and Selective Series of Itk Inhibitors via a Template-Hopping Strategy
Inhibition of Itk potentially constitutes
a novel, nonsteroidal
treatment for asthma and other T-cell mediated diseases. In-house
kinase cross-screening resulted in the identification of an aminopyrazole-based
series of Itk inhibitors. Initial work on this series highlighted
selectivity issues with several other kinases, particularly AurA and
AurB. A template-hopping strategy was used to identify a series of
aminobenzothiazole Itk inhibitors, which utilized an inherently more
selective hinge binding motif. Crystallography and modeling were used
to rationalize the observed selectivity. Initial exploration of the
SAR around this series identified potent Itk inhibitors in both enzyme
and cellular assays