UCL-TRO-1938 (Compound 1938) is a selective, allosteric activator of PI3Kα with EC50 of 60 uM (based on in vitro lipid kinase activity), directly activates PI3Kα signalling in cells.
UCL-TRO-1938 displays dissociation constant (Kd) values of 36  µM and 16 µM by rsurface plasmon resonance and differential scanning fluorimetry assays, respectively.
UCL-TRO-1938-stimulated PI3Kα activity is fully inhibited by the nanomolar potency ATP-competitive PI3Kα-selective inhibitor BYL719.
UCL-TRO-1938 does not affect the activity of the other PI3K isoforms in the panel (PI3Kβ, PI3Kγ, PI3Kδ, PI3K-C2α and VPS34) or the PI3K-related kinases PI4Kβ, mTOR and DNA-PK.
UCL-TRO-1938 stimulates PI3Kα by enhancing multiple events associated with natural and mutation-mediated PI3Kα activation. increases PtdIns(3,4,5)P3 levels in mouse embryonic fibroblasts (MEFs) with EC50 of 5 uM, increases pAKT(S473) levels in a concentration-dependent manner in MEFs with PI3Kα-WT with EC50 of 2-4 uM.
UCL-TRO-1938 dose-dependently increases metabolic activity in PI3Kα-WT but not in PI3Kα-KO MEFs with EC50 of 0.5 uM, induces cell cycle progression and an increase in cell numbe.
UCL-TRO-1938 demontrates cardioprotection effect and stimulates nerve regeneration in the rat sciatic nerve crush model of peripheral nerve injury and regeneration.