3 research outputs found
Discovery and in Vivo Evaluation of Dual PI3Kβ/δ Inhibitors
Structure-based rational design led to the synthesis
of a novel series of potent PI3K inhibitors. The optimized pyrrolopyridine
analogue <b>63</b> was a potent and selective PI3Kβ/δ
dual inhibitor that displayed suitable physicochemical properties
and pharmacokinetic profile for animal studies. Analogue <b>63</b> was found to be efficacious in animal models of inflammation including
a keyhole limpet hemocyanin (KLH) study and a collagen-induced arthritis
(CIA) disease model of rheumatoid arthritis. These studies highlight
the potential therapeutic value of inhibiting both the PI3Kβ
and δ isoforms in the treatment of a number of inflammatory
diseases