UCL-TRO-1938

UCL-TRO-1938 is an allosteric activator of PI3Kα.¹ It binds to PI3Kα in a surface plasmon resonance (SPR) assay (K_d = 36 µM) and induces PI3Kα activation in a cell-free assay when used at concentrations of 25 and 50 µM, an effect that can be reversed by the PI3Kα inhibitor BYL719 . UCL-TRO-1938 increases PtdIns-(3,4,5)-P₃ and phosphorylated Akt levels in mouse embryonic fibroblasts (MEFs; EC₅₀s = 5 and 2-4 µM, respectively). Ex vivo, UCL-TRO-1938 increases tissue survival and decreases infarct size in perfused rat hearts. In vivo, UCL-TRO-1938 (10 mg/kg) reduces infarct size in a mouse model of ischemia-reperfusion injury induced by left anterior descending (LAD) coronary artery occlusion. It also increases the number of motor neurons and innervation of neuromuscular junctions in a rat model of sciatic nerve crush injury.