PI3K/mTOR Inhibitor-9

PI3K/mTOR Inhibitor-9 (Compound 1) is a potent mTOR and PI3K inhibitor with IC50 values of 38 nM, 6.6 μM, 6.6 μM and 0.8 μM against mTOR (phospho-S6 cellular assay), PI3Kα, PI3Kγ and PI3Kδ, respectively[1].

Signaling Pathways >> PI3K/Akt/mTOR >> mTOR

Signaling Pathways >> PI3K/Akt/mTOR >> PI3K

Research Areas >> Neurological Disease

mTOR:38 nM (IC50, phospho-S6 cellular assay)

PI3Kα:6.6 μM (IC50)

PI3Kβ:>10 μM (IC50)

PI3Kγ:6.6 μM (IC50)

PI3Kδ:0.8 μM (IC50)

mTOR:16 nM (IC50, Ser240/244 cellular assay)

PI3K/mTOR Inhibitor-9 (Compound 1) shows good selectivity over the related kinases PI3Kα, β and γ, although with lower selectivity over PI3Kδ[1]. PI3K/mTOR Inhibitor-9 inhibits CYP2D6 (IC50 = 1.98 µM) and shows time-dependent inhibition (TDI) of CYP3A4 (rate of enzyme inhibition, kobs = 0.080 /min)[1]. PI3K/mTOR Inhibitor-9 shows good permeability with no sign of P-gp efflux (B-A/A-B: 0.95) [1].

[1]. Bonazzi S, et al. Discovery of a Brain-Penetrant ATP-Competitive Inhibitor of the Mechanistic Target of Rapamycin (mTOR) for CNS Disorders. J Med Chem. 2020 Feb 13;63(3):1068-1083.