AS-605240 (648450-29-7) is a potent and selective inhibitor of PI 3-kinase γ (PI 3-Kγ), IC50 = 8 nM displaying 30-fold selectivity over PI 3-Kδ and PI 3-Kβ and 7.5-fold selectivity over PI 3-Kα1. Suppresses joint inflammation in two distinct mouse models1. Ameliorates surgical brain injury2, colitis3, intimal hyperplasia-induced inflammatory processes4 and renal injury/fibrosis5 in rodent models. Orally active.
1) Camps et al. (2005), Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis; Nature Med., 11 936
2) Huang et al. (2015), Phosphoinositide 3-Kinase Gamma Contributes to Neuroinflammation ina Rat Model of Surgical Brain Injury; J. Neurosci., 35 10390
3) Peng et al. (2010), Inhibition of phosphoinositide 3-kinase ameliorates dextran sodium sulfate-induced colitis in mice; J. Pharmacol. Exp. Ther., 332 46
4) Smimova et al. (2014), Targeting PI3Kγ activity decreases vascular trauma-induced intimal hyperplasia through modulation of the Th1 response; J. Exp. Med., 211 1779
5) Yu et al. (2018), A blockade of PI3Kγ signaling effectively mitigates angiotensin II-induced renal injury and fibrosis in a mouse model; Sci. Rep., 8 10988