Description |
TG100-115 inhibited PI3Kγ and PI3K&delta, (IC50 values of 83 and 235 nM, respectively), whereas both PI3Kα and PI3Kβ were relatively unaffected (IC50 values >1 µ M). In 133 protein kinase panel, TG100-115 did not show significant inhibition (IC50 values >1 µ M). In a mouse murine asthma model, TG100-115 markedly reduced the pulmonary eosinophilia and the concomitant interleukin-13 and mucin accumulation. TG100-115 also inhibited inflammatory patterns in mouse smoke model. In a rat and porcine model of myocardial infraction TG100-115 potently inhibited edema and inflammation in response to multiple mediators, including vascular endothelial growth factor and platelet-activating factor. By contrast, endothelial cell mitogenesis, a repair process important to tissue survival after ischemic damage, was not disrupted. |
Reference |
1. Doukas, J., et al. J. Pharmacol. Exp. Ther. 2009, 328, 758
2. Doukas, J., et al. Biochem. Soc. Trans. 2007, 35, 204
3. Doukas, J., et al. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 19866. |